Pediatrics

Caring for a newborn can be a source of joy for family physicians (FPs). In this article, we examine care provided in the first month of life, including a thorough physical examination, safe hospital discharge procedures, assessment of neonatal feeding, evaluation of jaundice and fever, and prevention of sudden infant death syndrome (SIDS). In addition, we describe how FPs can support women of childbearing age between pregnancies, with the goal of reducing the risk of adverse outcomes in future pregnancies. (See “Your role in risk assessment and interventions during the interconception period.”)

 

 

Ensuring a thorough exam, making use of a discharge checklist

Before parents leave the hospital with their newborn, it is essential that they receive written and verbal counseling on important issues in neonatal care. A discharge checklist can help make sure all topics have been covered.¹ A hearing screen and pulse oximetry before discharge are required for all newborns in most states, in addition to important preventive counseling for parents. TABLE 1² and TABLE 2² summarize important newborn physical exam findings and common skin conditions. Parents should be given additional written information regarding prevention of SIDS and proper use of car seats.

Hospital physicians should assess maternal medical and psychosocial readiness for discharge. Through shared decision-making with the newborn’s parents, physicians should create a plan for outpatient follow-up. Assessment through a physician home visit can provide safe and effective care similar to what is provided at a visit to an office medical practice.^3-7 A follow-up appointment should be made 2 to 5 days before discharge, preferably connecting the newborn to a medical home where comprehensive health care services are offered.^1,5,6,8

Age, gestational age, risk factors for hyperbilirubinemia, and the timing and level of bilirubin testing should be considered when establishing a follow-up interval. Most newborns who are discharged before 72 hours of age should have a follow-up visit in 2 days; a newborn who has a recognized risk factor for a health problem should be seen sooner. Newborns in the “low-risk zone” (ie, no recognized risk factors) should be seen based on age at discharge or need for breastfeeding support.⁹

Tracking baby’s weight, ensuring proper feeding

A newborn who is discharged at 24 hours of life, or sooner, should be seen in the office within 2 days of discharge to 1) ensure that he (she) is getting proper nutrition and 2) monitor his weight^1,3,5 (TABLE 3^10-13). All newborns should be seen again at 2 weeks of life, with additional visits more frequently if there are concerns about nutrition.¹

Recording an accurate weight is critical; the newborn should be weighed completely undressed and without a diaper. Healthy newborns can safely lose up to 10% of birth weight within the first week of life; they should be back to their birth weight by approximately 2 weeks of life.^10,11 A healthy newborn loses approximately 0.5 to 1 oz a day;¹¹ greater than 10% loss of birth weight should trigger a thorough medical work-up and feeding assessment.

Breastfeeding. For breastfeeding mothers, physicians should recommend on-demand feeding or a feeding at least every 2 or 3 hours. Adequate intake in breastfed infants can be intimidating for new parents to monitor, but they can use a written chart or any of several available smartphone applications to document length and timing of feeds and frequency of urination and bowel movements. By the fifth day of life, a newborn should be having at least 6 voids and 3 or 4 stools a day.^10-12

In addition, physicians can counsel parents on what to look for—in the mother and the newborn—to confirm that breastfeeding is successful, with adequate nutritional intake (TABLE 3^10-13). Physicians should recommend against providing a pacifier to breastfeeding infants during the first several weeks of life—or until breastfeeding is well established (usually at 3 or 4 weeks of age). The World Health Organization (WHO) recommends against providing bottles, pacifiers, and artificial nipples to breastfeeding newborns.¹⁴ Liquids other than colostrum or breast milk should not be given unless there is a documented medical need, such as inadequate weight gain or feeding difficulty.¹⁵ If the newborn experiences early latch difficulties, supplementation with expressed breast milk is preferable to supplementation with formula. Assistance from a trained lactation consultant is a key element in the support of the breastfeeding dyad.^11,12,16

Breastfeeding optimizes development of the newborn’s immune system, thus bolstering disease prevention; it also assists with maternal postpartum weight loss and psychological well-being. Exclusively or primarily formula-fed newborns are at increased risk of gastrointestinal, ear, and respiratory infections throughout infancy and childhood; type 1 diabetes mellitus; asthma; childhood and adult obesity; and leukemia.^17,18 Mothers who feed their newborn primarily formula increase their own risk of obesity, type 2 diabetes mellitus, ovarian and breast cancer, and depression.^17-22

Infant feeding is a personal and family choice but, in the absence of medical contraindications—such as maternal human immunodeficiency virus infection and galactosemia—exclusive breastfeeding should be recommended.^17,18 FPs are well suited to support the mother–infant breastfeeding dyad in the neonatal period, based on expert recommendations. Specifically, the American Academy of Family Physicians (AAFP) and American Academy of Pediatrics (AAP) recommend that all infants be exclusively breastfed for the first 6 months of life and continue some breastfeeding through the first year or longer.^17,18 WHO recommends breastfeeding until 24 months of age—longer if mother and infant want to, unless breastfeeding is contraindicated.^14,17,18

Physicians should provide up-to-date information to parents regarding the risks and benefits of feeding choices. Support for breastfeeding mothers postnatally has been shown to be helpful in lengthening the time of exclusive breastfeeding.¹² Certain medications pass through breast milk, and updated guides to medication cautions can be found at the National Institutes of Health’s LACTMED Web site (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm).¹³ In many cases, when a maternal medication is incompatible with breastfeeding, the family physician can consider substituting another appropriate medication that is compatible.

Physician recommendation and support improves the rate of breastfeeding, but many mother–infant dyads require additional support to maintain breastfeeding for the recommended duration; such support can take the form of a certified lactation consultant or counselor, doula, or peer counselor.^23-25 Although structured breastfeeding education in the antenatal period has been demonstrated to be effective in improving breastfeeding initiation and duration, recent research shows that support groups and assistance from the professionals previously mentioned also improve the breastfeeding rate.^26-28

Adequate intake in breastfed infants can be intimidating for new parents to monitor, but they can use a written chart or any of several available smartphone applications.

The AAFP recommends that FPs’ offices adopt specific, evidence-based practices that can have an impact on breastfeeding initiation and duration. Such practices include phone and in-person breastfeeding support from nursing staff and removing any formula advertisements from the office.¹⁷

Formula feeding. When parents choose formula feeding, most infants tolerate cow’s milk-based formula.²⁹ For healthy term infants, differences between brands of formula are generally insignificant. Soy-protein formulas are of value only if lactose intolerance is strongly suspected, such as after prolonged episodes of loose stools. Even then, intolerance is usually transient and cow’s milk-based formula can be tried again in 2 to 4 weeks.

Physicians should recommend 20 kcal/oz of iron-fortified formula for infants who are fed formula—except in special circumstances, such as premature newborns, who may require a more calorie-dense formula. Parents should pay special attention to the manufacturer’s instructions for mixing formula with water because overdilution can cause hyponatremia. Typical volume for newborns should be at least 15 to 30 mL/feed for the first few days; newborns should not go more than 4 hours between feedings. Within the first week, newborns will start taking 60 to 90 mL/feed and increase that gradually to approximately 120 mL/feed by the end of the first month of life. On average, infants need a little more than 100 kcal/kg of body weight a day; for a 3.5-kg infant, that is at least 500 mL of formula over the course of a day.^17,22

Because formula does not contain fluoride, physicians should recommend that parents mix formula that is provided as a powder with fluoridated water. Low-iron formula offers no advantage; feeding with it will cause iron-deficiency anemia in most infants.

When tongue-tie interferes with feeding

Tongue-tie—or ankyloglossia, an atypically short or thick lingual frenulum—is present in 3% to 16% of all births. The condition can make breastfeeding difficult; result in poor neonatal weight gain; and cause sore nipples in 25% to 44% of cases.³⁰ Once tongue-tie is noted, the physician should talk to the mother about the history of feeding success, including whether her nipples are sore and whether the newborn is having difficulty feeding (ie, transferring milk). The Hazelbaker Assessment Tool for Lingual Frenulum Function and the simpler Bristol Tongue Assessment Tool can be used to assess the severity of tongue-tie.^30-35

When tongue-tie interferes with feeding, a physician who is not trained in treatment can refer the mother and infant to a specialist in the community. Frenotomy has been used for many years as a treatment for tongue-tie; improvement in nipple pain and the mother-reported breastfeeding score have been reported postoperatively in several studies.^30-33

Ensure proper vitamin D intake through supplementation

Newborns should consume 400 IU/d of supplemental vitamin D to prevent deficiency and its clinical manifestation, rickets, or other associated abnormalities of calcium metabolism. Deficiency of vitamin D has also been linked to a number of other conditions, including developmental delay and, possibly, type 1 diabetes mellitus in childhood and cardiovascular disease later in life.³⁶

Newborns should consume 400 IU/d of supplemental vitamin D to prevent deficiency and its clinical manifestation, rickets, or other associated abnormalities of calcium metabolism.

In the first months of life, few infants who are solely formula-fed will consume a full liter daily; for them, supplementation of vitamin D for at least one month should be prescribed.³⁵ For breastfed infants, high-dosage maternal vitamin D supplementation may be effective, precluding infant oral vitamin D supplementation³⁶; however, neither the AAFP nor the AAP has issued guidance promoting maternal supplementation in lieu of direct oral infant supplementation.³⁷

Jaundice prevention—and recognition

An elevated bilirubin level is seen in most newborns in the first days of life because of increased production and decreased clearance of bilirubin—a condition known as physiologic jaundice. Conditions that aggravate physiologic hyperbilirubinemia include inborn errors of metabolism, ABO blood-group incompatibility, hemoglobin variants, and inflammatory states such as sepsis. It is important to distinguish physiologic jaundice from exaggerated physiologic and pathologic forms of hyperbilirubinemia; the latter is a medical emergency. Before we get to that, a word about prevention.

Prevention. Because poor caloric intake and dehydration are associated with hyperbilirubinemia, physicians should advise breastfeeding mothers to feed their newborn at least 8 to 12 times daily during the first week of life. However, routine supplementation of liquids other than breast milk should be discouraged in newborns who are not dehydrated.³⁸

The total serum bilirubin level should be tested in every newborn who has clinical jaundice in the first 24 hours of life.

All pregnant women should be tested for ABO and Rh (D) blood types and undergo serum screening for isoimmune antibodies. Randomized trials have demonstrated that the incidence of significant hyperbilirubinemia can be reduced if, for Rh-negative mothers and those who did not undergo prenatal blood-group testing, infant cord blood is tested for 1) ABO and Rh (D) types and 2) direct antibody (Coombs’ test).^38,39

Screening and assessment. It is recommended that all newborns be screened for jaundice before discharge by 1) assessment of clinical risk factors or 2) testing of transcutaneous bilirubin (TcB) or total serum bilirubin (TSB). Furthermore, because evidence shows that treating clinical jaundice can improve outcomes and rehospitalization, TSB should be measured in every newborn who has clinical jaundice in the first 24 hours of life. Measurement of TcB or TSB should also be performed on all infants in whom there appears to be clinical jaundice that is excessive for age.^38,39

During routine clinical care, TcB measurement provides a reasonable estimate of the TSB level in healthy newborns at levels less than 15 mg/dL,⁴⁰ although TcB testing might not be available in the outpatient office. An AAP management algorithm can help determine when a newborn should be seen for outpatient follow-up based on risk of hyperbilirubinemia; higher-risk newborns should be reevaluated in 24 hours.⁹ Outpatient visual assessment of jaundice for cephalocaudal progression—in a well-lit room, with a fully undressed newborn—correlates well with TSB test results. However, visual assessment should not be used alone to screen for hyperbilirubinemia; recent studies have demonstrated that such assessment lacks clinical reliability.⁴⁰

Laboratory assessment. All bilirubin levels should be interpreted based on the newborn’s age in hours. The need for phototherapy should be based on the zone (low, low-intermediate, high-intermediate, or high, as categorized in the AAP nomogram³⁸ in which the TSB level falls. TABLE 4^38-40 provides recommendations for laboratory studies based on risk factors. Standard curves for risk stratification have been developed by the AAP.^37,38

Treatment. Decisions to initiate treatment should be based on the AAP algorithm.³⁸ When initiating phototherapy, precautions include ensuring adequate fluid intake, patching eyes, and monitoring temperature. Phototherapy can generally be stopped when the TSB level falls by 5 mg/dL or below 14 mg/dL. Home phototherapy, using a fiberoptic blanket, for uncomplicated jaundice (in carefully selected newborns with reliable parents) allows continued breastfeeding and bonding with the family, and can significantly decrease the rate of rehospitalization for infants older than 34 weeks.⁴¹

Breastfeeding is often associated with a higher bilirubin level than is seen in infants fed formula exclusively; increasing the frequency of feeding usually reduces the bilirubin level. So-called breast-milk jaundice is a delayed, but common, form of jaundice that is usually diagnosed in the second week of life and peaks by the end of the second week, resolving gradually over one to 4 months. If evaluation reveals no pathologic source, breastfeeding can generally be continued. Temporary discontinuation of breastfeeding to consider a diagnosis of breast-milk jaundice or other reasons for an elevated bilirubin level increases the risk of breastfeeding failure and is usually unnecessary.^12,37,39

Fever—a full work-up, thorough history are key

Concern about serious bacterial illness (SBI) makes the evaluation of fever critical for those who care for newborns. Many studies have attempted to identify which newborns might be able to be cared for safely as outpatients to prevent unnecessary testing and antibiotics.^5,42 Regrettably, SBI in infants remains difficult to predict, and protocols that have been developed may miss as many as 1 of every 10 newborns who has SBI.⁴³ Initial management of all infants 28 days old or younger with fever must therefore include a full work-up, including lumbar puncture and empiric antibiotics.⁴⁴

Evaluation. When an infant younger than 28 days has a fever, the physician should first verify that the temperature was taken rectally and how it was documented. In an infant who has a history of prematurity, it is crucial to correct for chronological age when deciding on proper evaluation.

Additional important findings in the history include a significant change in behavior, associated symptoms, and exposure to sick contacts. The maternal and birth history, including prolonged rupture of membranes, colonization with group B Streptococcus, administration of antibiotics at delivery, and genital herpes simplex virus (HSV) infection may suggest a cause for fever.⁴⁵

The evaluation of fever might include the white blood cell (WBC) count, blood culture, measurement of markers of inflammation, urine studies, lumbar puncture, stool culture, and chest radiograph. Traditionally, the WBC count has been utilized as a standard marker for sepsis, although it has a low sensitivity and specificity for SBI, especially in newborns.⁴⁶ Blood cultures should be obtained routinely in the newborn with fever, and before antibiotics are administered in older infants.

Procalcitonin (PCT; a calcitonin precursor) and the inflammatory marker C-reactive protein (CRP) have been shown, in several large studies, to have relatively high sensitivity and specificity for SBI; measurement of these constituents may enhance detection of serious illness.^46-49 In a large study of 2047 febrile infants older than 30 months, the PCT level was determined to be more accurate than the CRP level, the WBC count, and the absolute neutrophil count in predicting SBI.^48,49 PCT shows the most promise for preventing a full fever work-up and empiric antibiotics. It has not yet been widely translated into practice, however, because of a lack of clear guidance on how to combine PCT levels with other laboratory markers and clinical decision-making.^48-50

Urinalysis (UA) should be obtained for all newborns who present with fever. Traditionally, it was recommended that urine should be cultured for all newborns with fever; however, more recent data show that the initial urinalysis is much more sensitive than once thought. In a study, UA was positive (defined as pyuria or a positive leukocyte esterase test, or both) in all but 1 of 203 infants who had bacteremic UTI (sensitivity, 99.5%).⁵¹

The procalcitonin level was determined to be more accurate than the C-reactive protein level, the white blood cell count, and the absolute neutrophil count in predicting serious bacterial illness.

Stool culture is necessary in newborns only when they present with blood or mucus in diarrhea. Lumbar puncture should be performed in all febrile newborns and all newborns for whom empiric antibiotics have been prescribed.^43,44 A chest radiograph may be useful in diagnosis when a newborn has any other sign of pulmonary disease: respiratory rate >50/min, retractions, wheezing, grunting, stridor, nasal flaring, cough, and positive findings on lung examination.^43,44

Treatment. Management for all newborns who have a rectal temperature ≥38° C includes admission to the hospital and empiric antibiotics; guidance is based primarily on expert consensus. Common pathogens for SBI include group B Strep, Escherichia coli, Enterococcus spp., and Listeria monocytogenes.^43,44 Empiric antibiotics, including ampicillin (to cover L monocytogenes) and cefotaxime or gentamicin should be started immediately after sending for blood, urine, and cerebrospinal fluid (CSF) cultures.^43-45

Management for all newborns who have rectal temperature ≥38° C includes admission to the hospital and empiric antibiotics.

All infants who are ill-appearing or have vesicles, seizures, or a maternal history of genital HSV infection should also be started on empiric acyclovir. Vesicles should be cultured and CSF should be sent for HSV DNA polymerase chain reaction before acyclovir is administered.^43-45

Sudden infant death syndrome: Steps to take to minimize risk

SIDS is defined as the sudden death of a child younger than 1 year that remains unexplained after a thorough case investigation and comprehensive review of the clinical history. The risk of SIDS in the United States is less than 1 for every 1000 live births; incidence peaks between 2 and 4 months of age.⁵² In the United States, SIDS and other sleep-related infant deaths, such as strangulation in bed or accidental suffocation, account for more than 4000 deaths a year.⁵³ The incidence of SIDS declined markedly after the “Back to Sleep” campaign was launched in 2003, but has leveled off since 2005.^53-55

Numerous risk factors for SIDS have been identified, including maternal factors (young maternal age, maternal smoking during pregnancy, late or no prenatal care) and infant and environmental factors (prematurity, low birth weight, male gender, prone sleeping position, sleeping on a soft surface or with bedding accessories, bed-sharing (ie, sleeping in the parents’ bed), and overheating. In many cases, the risk factors are modifiable; sleeping in the prone position is the most meaningful modifiable risk factor.

Home monitors have not been proven to reduce the incidence of SIDS and are not recommended for that purpose.

To minimize the risk for SIDS, parents should be educated on the risk factors—prenatally as well as at each infant well visit. Home monitors have not been proven to reduce the incidence of SIDS and are not recommended for that purpose.^54-57 Although evidence is strongest for supine positioning as a preventive intervention for SIDS, other evidence-based recommendations include use of a firm sleep surface; breastfeeding; use of a pacifier; room-sharing with parents without bed-sharing; routine immunization; avoidance of overheating; avoiding falling asleep with the infant on a chair or couch; and avoiding exposure to tobacco smoke, alcohol, and drugs of abuse.^55,56 A recent systematic review showed that large-scale community interventions and education campaigns can play a significant role in parental and community adoption of safe sleep recommendations; however, families and communities rarely exhibit complete adherence to safe sleep practices.⁵⁷

Other concerns in the first month of life and immediately beyond

In TABLE 5,² we list additional common newborn problems not reviewed in the text of this article and summarize evidence-based treatment strategies.

CORRESPONDENCE
Scott Hartman, MD, Associate Professor, Department of Family Medicine, University of Rochester Medical Center, 777 South Clinton Avenue, Rochester, NY 14620; scott_hartman@urmc.rochester.edu.

Acknowledgement
We thank Nancy Phillips for her assistance in the preparation of this article.

Caring for a newborn can be a source of joy for family physicians (FPs). In this article, we examine care provided in the first month of life, including a thorough physical examination, safe hospital discharge procedures, assessment of neonatal feeding, evaluation of jaundice and fever, and prevention of sudden infant death syndrome (SIDS). In addition, we describe how FPs can support women of childbearing age between pregnancies, with the goal of reducing the risk of adverse outcomes in future pregnancies. (See “Your role in risk assessment and interventions during the interconception period.”)

 

 

Ensuring a thorough exam, making use of a discharge checklist

Before parents leave the hospital with their newborn, it is essential that they receive written and verbal counseling on important issues in neonatal care. A discharge checklist can help make sure all topics have been covered.¹ A hearing screen and pulse oximetry before discharge are required for all newborns in most states, in addition to important preventive counseling for parents. TABLE 1² and TABLE 2² summarize important newborn physical exam findings and common skin conditions. Parents should be given additional written information regarding prevention of SIDS and proper use of car seats.

Hospital physicians should assess maternal medical and psychosocial readiness for discharge. Through shared decision-making with the newborn’s parents, physicians should create a plan for outpatient follow-up. Assessment through a physician home visit can provide safe and effective care similar to what is provided at a visit to an office medical practice.^3-7 A follow-up appointment should be made 2 to 5 days before discharge, preferably connecting the newborn to a medical home where comprehensive health care services are offered.^1,5,6,8

Age, gestational age, risk factors for hyperbilirubinemia, and the timing and level of bilirubin testing should be considered when establishing a follow-up interval. Most newborns who are discharged before 72 hours of age should have a follow-up visit in 2 days; a newborn who has a recognized risk factor for a health problem should be seen sooner. Newborns in the “low-risk zone” (ie, no recognized risk factors) should be seen based on age at discharge or need for breastfeeding support.⁹

Tracking baby’s weight, ensuring proper feeding

A newborn who is discharged at 24 hours of life, or sooner, should be seen in the office within 2 days of discharge to 1) ensure that he (she) is getting proper nutrition and 2) monitor his weight^1,3,5 (TABLE 3^10-13). All newborns should be seen again at 2 weeks of life, with additional visits more frequently if there are concerns about nutrition.¹

Recording an accurate weight is critical; the newborn should be weighed completely undressed and without a diaper. Healthy newborns can safely lose up to 10% of birth weight within the first week of life; they should be back to their birth weight by approximately 2 weeks of life.^10,11 A healthy newborn loses approximately 0.5 to 1 oz a day;¹¹ greater than 10% loss of birth weight should trigger a thorough medical work-up and feeding assessment.

Breastfeeding. For breastfeeding mothers, physicians should recommend on-demand feeding or a feeding at least every 2 or 3 hours. Adequate intake in breastfed infants can be intimidating for new parents to monitor, but they can use a written chart or any of several available smartphone applications to document length and timing of feeds and frequency of urination and bowel movements. By the fifth day of life, a newborn should be having at least 6 voids and 3 or 4 stools a day.^10-12

In addition, physicians can counsel parents on what to look for—in the mother and the newborn—to confirm that breastfeeding is successful, with adequate nutritional intake (TABLE 3^10-13). Physicians should recommend against providing a pacifier to breastfeeding infants during the first several weeks of life—or until breastfeeding is well established (usually at 3 or 4 weeks of age). The World Health Organization (WHO) recommends against providing bottles, pacifiers, and artificial nipples to breastfeeding newborns.¹⁴ Liquids other than colostrum or breast milk should not be given unless there is a documented medical need, such as inadequate weight gain or feeding difficulty.¹⁵ If the newborn experiences early latch difficulties, supplementation with expressed breast milk is preferable to supplementation with formula. Assistance from a trained lactation consultant is a key element in the support of the breastfeeding dyad.^11,12,16

Breastfeeding optimizes development of the newborn’s immune system, thus bolstering disease prevention; it also assists with maternal postpartum weight loss and psychological well-being. Exclusively or primarily formula-fed newborns are at increased risk of gastrointestinal, ear, and respiratory infections throughout infancy and childhood; type 1 diabetes mellitus; asthma; childhood and adult obesity; and leukemia.^17,18 Mothers who feed their newborn primarily formula increase their own risk of obesity, type 2 diabetes mellitus, ovarian and breast cancer, and depression.^17-22

Infant feeding is a personal and family choice but, in the absence of medical contraindications—such as maternal human immunodeficiency virus infection and galactosemia—exclusive breastfeeding should be recommended.^17,18 FPs are well suited to support the mother–infant breastfeeding dyad in the neonatal period, based on expert recommendations. Specifically, the American Academy of Family Physicians (AAFP) and American Academy of Pediatrics (AAP) recommend that all infants be exclusively breastfed for the first 6 months of life and continue some breastfeeding through the first year or longer.^17,18 WHO recommends breastfeeding until 24 months of age—longer if mother and infant want to, unless breastfeeding is contraindicated.^14,17,18

Physicians should provide up-to-date information to parents regarding the risks and benefits of feeding choices. Support for breastfeeding mothers postnatally has been shown to be helpful in lengthening the time of exclusive breastfeeding.¹² Certain medications pass through breast milk, and updated guides to medication cautions can be found at the National Institutes of Health’s LACTMED Web site (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm).¹³ In many cases, when a maternal medication is incompatible with breastfeeding, the family physician can consider substituting another appropriate medication that is compatible.

Physician recommendation and support improves the rate of breastfeeding, but many mother–infant dyads require additional support to maintain breastfeeding for the recommended duration; such support can take the form of a certified lactation consultant or counselor, doula, or peer counselor.^23-25 Although structured breastfeeding education in the antenatal period has been demonstrated to be effective in improving breastfeeding initiation and duration, recent research shows that support groups and assistance from the professionals previously mentioned also improve the breastfeeding rate.^26-28

Adequate intake in breastfed infants can be intimidating for new parents to monitor, but they can use a written chart or any of several available smartphone applications.

The AAFP recommends that FPs’ offices adopt specific, evidence-based practices that can have an impact on breastfeeding initiation and duration. Such practices include phone and in-person breastfeeding support from nursing staff and removing any formula advertisements from the office.¹⁷

Formula feeding. When parents choose formula feeding, most infants tolerate cow’s milk-based formula.²⁹ For healthy term infants, differences between brands of formula are generally insignificant. Soy-protein formulas are of value only if lactose intolerance is strongly suspected, such as after prolonged episodes of loose stools. Even then, intolerance is usually transient and cow’s milk-based formula can be tried again in 2 to 4 weeks.

Physicians should recommend 20 kcal/oz of iron-fortified formula for infants who are fed formula—except in special circumstances, such as premature newborns, who may require a more calorie-dense formula. Parents should pay special attention to the manufacturer’s instructions for mixing formula with water because overdilution can cause hyponatremia. Typical volume for newborns should be at least 15 to 30 mL/feed for the first few days; newborns should not go more than 4 hours between feedings. Within the first week, newborns will start taking 60 to 90 mL/feed and increase that gradually to approximately 120 mL/feed by the end of the first month of life. On average, infants need a little more than 100 kcal/kg of body weight a day; for a 3.5-kg infant, that is at least 500 mL of formula over the course of a day.^17,22

Because formula does not contain fluoride, physicians should recommend that parents mix formula that is provided as a powder with fluoridated water. Low-iron formula offers no advantage; feeding with it will cause iron-deficiency anemia in most infants.

When tongue-tie interferes with feeding

Tongue-tie—or ankyloglossia, an atypically short or thick lingual frenulum—is present in 3% to 16% of all births. The condition can make breastfeeding difficult; result in poor neonatal weight gain; and cause sore nipples in 25% to 44% of cases.³⁰ Once tongue-tie is noted, the physician should talk to the mother about the history of feeding success, including whether her nipples are sore and whether the newborn is having difficulty feeding (ie, transferring milk). The Hazelbaker Assessment Tool for Lingual Frenulum Function and the simpler Bristol Tongue Assessment Tool can be used to assess the severity of tongue-tie.^30-35

When tongue-tie interferes with feeding, a physician who is not trained in treatment can refer the mother and infant to a specialist in the community. Frenotomy has been used for many years as a treatment for tongue-tie; improvement in nipple pain and the mother-reported breastfeeding score have been reported postoperatively in several studies.^30-33

Ensure proper vitamin D intake through supplementation

Newborns should consume 400 IU/d of supplemental vitamin D to prevent deficiency and its clinical manifestation, rickets, or other associated abnormalities of calcium metabolism. Deficiency of vitamin D has also been linked to a number of other conditions, including developmental delay and, possibly, type 1 diabetes mellitus in childhood and cardiovascular disease later in life.³⁶

Newborns should consume 400 IU/d of supplemental vitamin D to prevent deficiency and its clinical manifestation, rickets, or other associated abnormalities of calcium metabolism.

In the first months of life, few infants who are solely formula-fed will consume a full liter daily; for them, supplementation of vitamin D for at least one month should be prescribed.³⁵ For breastfed infants, high-dosage maternal vitamin D supplementation may be effective, precluding infant oral vitamin D supplementation³⁶; however, neither the AAFP nor the AAP has issued guidance promoting maternal supplementation in lieu of direct oral infant supplementation.³⁷

Jaundice prevention—and recognition

An elevated bilirubin level is seen in most newborns in the first days of life because of increased production and decreased clearance of bilirubin—a condition known as physiologic jaundice. Conditions that aggravate physiologic hyperbilirubinemia include inborn errors of metabolism, ABO blood-group incompatibility, hemoglobin variants, and inflammatory states such as sepsis. It is important to distinguish physiologic jaundice from exaggerated physiologic and pathologic forms of hyperbilirubinemia; the latter is a medical emergency. Before we get to that, a word about prevention.

Prevention. Because poor caloric intake and dehydration are associated with hyperbilirubinemia, physicians should advise breastfeeding mothers to feed their newborn at least 8 to 12 times daily during the first week of life. However, routine supplementation of liquids other than breast milk should be discouraged in newborns who are not dehydrated.³⁸

The total serum bilirubin level should be tested in every newborn who has clinical jaundice in the first 24 hours of life.

All pregnant women should be tested for ABO and Rh (D) blood types and undergo serum screening for isoimmune antibodies. Randomized trials have demonstrated that the incidence of significant hyperbilirubinemia can be reduced if, for Rh-negative mothers and those who did not undergo prenatal blood-group testing, infant cord blood is tested for 1) ABO and Rh (D) types and 2) direct antibody (Coombs’ test).^38,39

Screening and assessment. It is recommended that all newborns be screened for jaundice before discharge by 1) assessment of clinical risk factors or 2) testing of transcutaneous bilirubin (TcB) or total serum bilirubin (TSB). Furthermore, because evidence shows that treating clinical jaundice can improve outcomes and rehospitalization, TSB should be measured in every newborn who has clinical jaundice in the first 24 hours of life. Measurement of TcB or TSB should also be performed on all infants in whom there appears to be clinical jaundice that is excessive for age.^38,39

During routine clinical care, TcB measurement provides a reasonable estimate of the TSB level in healthy newborns at levels less than 15 mg/dL,⁴⁰ although TcB testing might not be available in the outpatient office. An AAP management algorithm can help determine when a newborn should be seen for outpatient follow-up based on risk of hyperbilirubinemia; higher-risk newborns should be reevaluated in 24 hours.⁹ Outpatient visual assessment of jaundice for cephalocaudal progression—in a well-lit room, with a fully undressed newborn—correlates well with TSB test results. However, visual assessment should not be used alone to screen for hyperbilirubinemia; recent studies have demonstrated that such assessment lacks clinical reliability.⁴⁰

Laboratory assessment. All bilirubin levels should be interpreted based on the newborn’s age in hours. The need for phototherapy should be based on the zone (low, low-intermediate, high-intermediate, or high, as categorized in the AAP nomogram³⁸ in which the TSB level falls. TABLE 4^38-40 provides recommendations for laboratory studies based on risk factors. Standard curves for risk stratification have been developed by the AAP.^37,38

Treatment. Decisions to initiate treatment should be based on the AAP algorithm.³⁸ When initiating phototherapy, precautions include ensuring adequate fluid intake, patching eyes, and monitoring temperature. Phototherapy can generally be stopped when the TSB level falls by 5 mg/dL or below 14 mg/dL. Home phototherapy, using a fiberoptic blanket, for uncomplicated jaundice (in carefully selected newborns with reliable parents) allows continued breastfeeding and bonding with the family, and can significantly decrease the rate of rehospitalization for infants older than 34 weeks.⁴¹

Breastfeeding is often associated with a higher bilirubin level than is seen in infants fed formula exclusively; increasing the frequency of feeding usually reduces the bilirubin level. So-called breast-milk jaundice is a delayed, but common, form of jaundice that is usually diagnosed in the second week of life and peaks by the end of the second week, resolving gradually over one to 4 months. If evaluation reveals no pathologic source, breastfeeding can generally be continued. Temporary discontinuation of breastfeeding to consider a diagnosis of breast-milk jaundice or other reasons for an elevated bilirubin level increases the risk of breastfeeding failure and is usually unnecessary.^12,37,39

Fever—a full work-up, thorough history are key

Concern about serious bacterial illness (SBI) makes the evaluation of fever critical for those who care for newborns. Many studies have attempted to identify which newborns might be able to be cared for safely as outpatients to prevent unnecessary testing and antibiotics.^5,42 Regrettably, SBI in infants remains difficult to predict, and protocols that have been developed may miss as many as 1 of every 10 newborns who has SBI.⁴³ Initial management of all infants 28 days old or younger with fever must therefore include a full work-up, including lumbar puncture and empiric antibiotics.⁴⁴

Evaluation. When an infant younger than 28 days has a fever, the physician should first verify that the temperature was taken rectally and how it was documented. In an infant who has a history of prematurity, it is crucial to correct for chronological age when deciding on proper evaluation.

Additional important findings in the history include a significant change in behavior, associated symptoms, and exposure to sick contacts. The maternal and birth history, including prolonged rupture of membranes, colonization with group B Streptococcus, administration of antibiotics at delivery, and genital herpes simplex virus (HSV) infection may suggest a cause for fever.⁴⁵

The evaluation of fever might include the white blood cell (WBC) count, blood culture, measurement of markers of inflammation, urine studies, lumbar puncture, stool culture, and chest radiograph. Traditionally, the WBC count has been utilized as a standard marker for sepsis, although it has a low sensitivity and specificity for SBI, especially in newborns.⁴⁶ Blood cultures should be obtained routinely in the newborn with fever, and before antibiotics are administered in older infants.

Procalcitonin (PCT; a calcitonin precursor) and the inflammatory marker C-reactive protein (CRP) have been shown, in several large studies, to have relatively high sensitivity and specificity for SBI; measurement of these constituents may enhance detection of serious illness.^46-49 In a large study of 2047 febrile infants older than 30 months, the PCT level was determined to be more accurate than the CRP level, the WBC count, and the absolute neutrophil count in predicting SBI.^48,49 PCT shows the most promise for preventing a full fever work-up and empiric antibiotics. It has not yet been widely translated into practice, however, because of a lack of clear guidance on how to combine PCT levels with other laboratory markers and clinical decision-making.^48-50

Urinalysis (UA) should be obtained for all newborns who present with fever. Traditionally, it was recommended that urine should be cultured for all newborns with fever; however, more recent data show that the initial urinalysis is much more sensitive than once thought. In a study, UA was positive (defined as pyuria or a positive leukocyte esterase test, or both) in all but 1 of 203 infants who had bacteremic UTI (sensitivity, 99.5%).⁵¹

The procalcitonin level was determined to be more accurate than the C-reactive protein level, the white blood cell count, and the absolute neutrophil count in predicting serious bacterial illness.

Stool culture is necessary in newborns only when they present with blood or mucus in diarrhea. Lumbar puncture should be performed in all febrile newborns and all newborns for whom empiric antibiotics have been prescribed.^43,44 A chest radiograph may be useful in diagnosis when a newborn has any other sign of pulmonary disease: respiratory rate >50/min, retractions, wheezing, grunting, stridor, nasal flaring, cough, and positive findings on lung examination.^43,44

Treatment. Management for all newborns who have a rectal temperature ≥38° C includes admission to the hospital and empiric antibiotics; guidance is based primarily on expert consensus. Common pathogens for SBI include group B Strep, Escherichia coli, Enterococcus spp., and Listeria monocytogenes.^43,44 Empiric antibiotics, including ampicillin (to cover L monocytogenes) and cefotaxime or gentamicin should be started immediately after sending for blood, urine, and cerebrospinal fluid (CSF) cultures.^43-45

Management for all newborns who have rectal temperature ≥38° C includes admission to the hospital and empiric antibiotics.

All infants who are ill-appearing or have vesicles, seizures, or a maternal history of genital HSV infection should also be started on empiric acyclovir. Vesicles should be cultured and CSF should be sent for HSV DNA polymerase chain reaction before acyclovir is administered.^43-45

Sudden infant death syndrome: Steps to take to minimize risk

SIDS is defined as the sudden death of a child younger than 1 year that remains unexplained after a thorough case investigation and comprehensive review of the clinical history. The risk of SIDS in the United States is less than 1 for every 1000 live births; incidence peaks between 2 and 4 months of age.⁵² In the United States, SIDS and other sleep-related infant deaths, such as strangulation in bed or accidental suffocation, account for more than 4000 deaths a year.⁵³ The incidence of SIDS declined markedly after the “Back to Sleep” campaign was launched in 2003, but has leveled off since 2005.^53-55

Numerous risk factors for SIDS have been identified, including maternal factors (young maternal age, maternal smoking during pregnancy, late or no prenatal care) and infant and environmental factors (prematurity, low birth weight, male gender, prone sleeping position, sleeping on a soft surface or with bedding accessories, bed-sharing (ie, sleeping in the parents’ bed), and overheating. In many cases, the risk factors are modifiable; sleeping in the prone position is the most meaningful modifiable risk factor.

Home monitors have not been proven to reduce the incidence of SIDS and are not recommended for that purpose.

To minimize the risk for SIDS, parents should be educated on the risk factors—prenatally as well as at each infant well visit. Home monitors have not been proven to reduce the incidence of SIDS and are not recommended for that purpose.^54-57 Although evidence is strongest for supine positioning as a preventive intervention for SIDS, other evidence-based recommendations include use of a firm sleep surface; breastfeeding; use of a pacifier; room-sharing with parents without bed-sharing; routine immunization; avoidance of overheating; avoiding falling asleep with the infant on a chair or couch; and avoiding exposure to tobacco smoke, alcohol, and drugs of abuse.^55,56 A recent systematic review showed that large-scale community interventions and education campaigns can play a significant role in parental and community adoption of safe sleep recommendations; however, families and communities rarely exhibit complete adherence to safe sleep practices.⁵⁷

Other concerns in the first month of life and immediately beyond

In TABLE 5,² we list additional common newborn problems not reviewed in the text of this article and summarize evidence-based treatment strategies.

CORRESPONDENCE
Scott Hartman, MD, Associate Professor, Department of Family Medicine, University of Rochester Medical Center, 777 South Clinton Avenue, Rochester, NY 14620; scott_hartman@urmc.rochester.edu.

Acknowledgement
We thank Nancy Phillips for her assistance in the preparation of this article.

Caring for a newborn can be a source of joy for family physicians (FPs). In this article, we examine care provided in the first month of life, including a thorough physical examination, safe hospital discharge procedures, assessment of neonatal feeding, evaluation of jaundice and fever, and prevention of sudden infant death syndrome (SIDS). In addition, we describe how FPs can support women of childbearing age between pregnancies, with the goal of reducing the risk of adverse outcomes in future pregnancies. (See “Your role in risk assessment and interventions during the interconception period.”)

 

 

Ensuring a thorough exam, making use of a discharge checklist

Before parents leave the hospital with their newborn, it is essential that they receive written and verbal counseling on important issues in neonatal care. A discharge checklist can help make sure all topics have been covered.¹ A hearing screen and pulse oximetry before discharge are required for all newborns in most states, in addition to important preventive counseling for parents. TABLE 1² and TABLE 2² summarize important newborn physical exam findings and common skin conditions. Parents should be given additional written information regarding prevention of SIDS and proper use of car seats.

Hospital physicians should assess maternal medical and psychosocial readiness for discharge. Through shared decision-making with the newborn’s parents, physicians should create a plan for outpatient follow-up. Assessment through a physician home visit can provide safe and effective care similar to what is provided at a visit to an office medical practice.^3-7 A follow-up appointment should be made 2 to 5 days before discharge, preferably connecting the newborn to a medical home where comprehensive health care services are offered.^1,5,6,8

Age, gestational age, risk factors for hyperbilirubinemia, and the timing and level of bilirubin testing should be considered when establishing a follow-up interval. Most newborns who are discharged before 72 hours of age should have a follow-up visit in 2 days; a newborn who has a recognized risk factor for a health problem should be seen sooner. Newborns in the “low-risk zone” (ie, no recognized risk factors) should be seen based on age at discharge or need for breastfeeding support.⁹

Tracking baby’s weight, ensuring proper feeding

A newborn who is discharged at 24 hours of life, or sooner, should be seen in the office within 2 days of discharge to 1) ensure that he (she) is getting proper nutrition and 2) monitor his weight^1,3,5 (TABLE 3^10-13). All newborns should be seen again at 2 weeks of life, with additional visits more frequently if there are concerns about nutrition.¹

Recording an accurate weight is critical; the newborn should be weighed completely undressed and without a diaper. Healthy newborns can safely lose up to 10% of birth weight within the first week of life; they should be back to their birth weight by approximately 2 weeks of life.^10,11 A healthy newborn loses approximately 0.5 to 1 oz a day;¹¹ greater than 10% loss of birth weight should trigger a thorough medical work-up and feeding assessment.

Breastfeeding. For breastfeeding mothers, physicians should recommend on-demand feeding or a feeding at least every 2 or 3 hours. Adequate intake in breastfed infants can be intimidating for new parents to monitor, but they can use a written chart or any of several available smartphone applications to document length and timing of feeds and frequency of urination and bowel movements. By the fifth day of life, a newborn should be having at least 6 voids and 3 or 4 stools a day.^10-12

In addition, physicians can counsel parents on what to look for—in the mother and the newborn—to confirm that breastfeeding is successful, with adequate nutritional intake (TABLE 3^10-13). Physicians should recommend against providing a pacifier to breastfeeding infants during the first several weeks of life—or until breastfeeding is well established (usually at 3 or 4 weeks of age). The World Health Organization (WHO) recommends against providing bottles, pacifiers, and artificial nipples to breastfeeding newborns.¹⁴ Liquids other than colostrum or breast milk should not be given unless there is a documented medical need, such as inadequate weight gain or feeding difficulty.¹⁵ If the newborn experiences early latch difficulties, supplementation with expressed breast milk is preferable to supplementation with formula. Assistance from a trained lactation consultant is a key element in the support of the breastfeeding dyad.^11,12,16

Breastfeeding optimizes development of the newborn’s immune system, thus bolstering disease prevention; it also assists with maternal postpartum weight loss and psychological well-being. Exclusively or primarily formula-fed newborns are at increased risk of gastrointestinal, ear, and respiratory infections throughout infancy and childhood; type 1 diabetes mellitus; asthma; childhood and adult obesity; and leukemia.^17,18 Mothers who feed their newborn primarily formula increase their own risk of obesity, type 2 diabetes mellitus, ovarian and breast cancer, and depression.^17-22

Infant feeding is a personal and family choice but, in the absence of medical contraindications—such as maternal human immunodeficiency virus infection and galactosemia—exclusive breastfeeding should be recommended.^17,18 FPs are well suited to support the mother–infant breastfeeding dyad in the neonatal period, based on expert recommendations. Specifically, the American Academy of Family Physicians (AAFP) and American Academy of Pediatrics (AAP) recommend that all infants be exclusively breastfed for the first 6 months of life and continue some breastfeeding through the first year or longer.^17,18 WHO recommends breastfeeding until 24 months of age—longer if mother and infant want to, unless breastfeeding is contraindicated.^14,17,18

Physicians should provide up-to-date information to parents regarding the risks and benefits of feeding choices. Support for breastfeeding mothers postnatally has been shown to be helpful in lengthening the time of exclusive breastfeeding.¹² Certain medications pass through breast milk, and updated guides to medication cautions can be found at the National Institutes of Health’s LACTMED Web site (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm).¹³ In many cases, when a maternal medication is incompatible with breastfeeding, the family physician can consider substituting another appropriate medication that is compatible.

Physician recommendation and support improves the rate of breastfeeding, but many mother–infant dyads require additional support to maintain breastfeeding for the recommended duration; such support can take the form of a certified lactation consultant or counselor, doula, or peer counselor.^23-25 Although structured breastfeeding education in the antenatal period has been demonstrated to be effective in improving breastfeeding initiation and duration, recent research shows that support groups and assistance from the professionals previously mentioned also improve the breastfeeding rate.^26-28

Adequate intake in breastfed infants can be intimidating for new parents to monitor, but they can use a written chart or any of several available smartphone applications.

The AAFP recommends that FPs’ offices adopt specific, evidence-based practices that can have an impact on breastfeeding initiation and duration. Such practices include phone and in-person breastfeeding support from nursing staff and removing any formula advertisements from the office.¹⁷

Formula feeding. When parents choose formula feeding, most infants tolerate cow’s milk-based formula.²⁹ For healthy term infants, differences between brands of formula are generally insignificant. Soy-protein formulas are of value only if lactose intolerance is strongly suspected, such as after prolonged episodes of loose stools. Even then, intolerance is usually transient and cow’s milk-based formula can be tried again in 2 to 4 weeks.

Physicians should recommend 20 kcal/oz of iron-fortified formula for infants who are fed formula—except in special circumstances, such as premature newborns, who may require a more calorie-dense formula. Parents should pay special attention to the manufacturer’s instructions for mixing formula with water because overdilution can cause hyponatremia. Typical volume for newborns should be at least 15 to 30 mL/feed for the first few days; newborns should not go more than 4 hours between feedings. Within the first week, newborns will start taking 60 to 90 mL/feed and increase that gradually to approximately 120 mL/feed by the end of the first month of life. On average, infants need a little more than 100 kcal/kg of body weight a day; for a 3.5-kg infant, that is at least 500 mL of formula over the course of a day.^17,22

Because formula does not contain fluoride, physicians should recommend that parents mix formula that is provided as a powder with fluoridated water. Low-iron formula offers no advantage; feeding with it will cause iron-deficiency anemia in most infants.

When tongue-tie interferes with feeding

Tongue-tie—or ankyloglossia, an atypically short or thick lingual frenulum—is present in 3% to 16% of all births. The condition can make breastfeeding difficult; result in poor neonatal weight gain; and cause sore nipples in 25% to 44% of cases.³⁰ Once tongue-tie is noted, the physician should talk to the mother about the history of feeding success, including whether her nipples are sore and whether the newborn is having difficulty feeding (ie, transferring milk). The Hazelbaker Assessment Tool for Lingual Frenulum Function and the simpler Bristol Tongue Assessment Tool can be used to assess the severity of tongue-tie.^30-35

When tongue-tie interferes with feeding, a physician who is not trained in treatment can refer the mother and infant to a specialist in the community. Frenotomy has been used for many years as a treatment for tongue-tie; improvement in nipple pain and the mother-reported breastfeeding score have been reported postoperatively in several studies.^30-33

Ensure proper vitamin D intake through supplementation

Newborns should consume 400 IU/d of supplemental vitamin D to prevent deficiency and its clinical manifestation, rickets, or other associated abnormalities of calcium metabolism. Deficiency of vitamin D has also been linked to a number of other conditions, including developmental delay and, possibly, type 1 diabetes mellitus in childhood and cardiovascular disease later in life.³⁶

Newborns should consume 400 IU/d of supplemental vitamin D to prevent deficiency and its clinical manifestation, rickets, or other associated abnormalities of calcium metabolism.

In the first months of life, few infants who are solely formula-fed will consume a full liter daily; for them, supplementation of vitamin D for at least one month should be prescribed.³⁵ For breastfed infants, high-dosage maternal vitamin D supplementation may be effective, precluding infant oral vitamin D supplementation³⁶; however, neither the AAFP nor the AAP has issued guidance promoting maternal supplementation in lieu of direct oral infant supplementation.³⁷

Jaundice prevention—and recognition

An elevated bilirubin level is seen in most newborns in the first days of life because of increased production and decreased clearance of bilirubin—a condition known as physiologic jaundice. Conditions that aggravate physiologic hyperbilirubinemia include inborn errors of metabolism, ABO blood-group incompatibility, hemoglobin variants, and inflammatory states such as sepsis. It is important to distinguish physiologic jaundice from exaggerated physiologic and pathologic forms of hyperbilirubinemia; the latter is a medical emergency. Before we get to that, a word about prevention.

Prevention. Because poor caloric intake and dehydration are associated with hyperbilirubinemia, physicians should advise breastfeeding mothers to feed their newborn at least 8 to 12 times daily during the first week of life. However, routine supplementation of liquids other than breast milk should be discouraged in newborns who are not dehydrated.³⁸

The total serum bilirubin level should be tested in every newborn who has clinical jaundice in the first 24 hours of life.

All pregnant women should be tested for ABO and Rh (D) blood types and undergo serum screening for isoimmune antibodies. Randomized trials have demonstrated that the incidence of significant hyperbilirubinemia can be reduced if, for Rh-negative mothers and those who did not undergo prenatal blood-group testing, infant cord blood is tested for 1) ABO and Rh (D) types and 2) direct antibody (Coombs’ test).^38,39

Screening and assessment. It is recommended that all newborns be screened for jaundice before discharge by 1) assessment of clinical risk factors or 2) testing of transcutaneous bilirubin (TcB) or total serum bilirubin (TSB). Furthermore, because evidence shows that treating clinical jaundice can improve outcomes and rehospitalization, TSB should be measured in every newborn who has clinical jaundice in the first 24 hours of life. Measurement of TcB or TSB should also be performed on all infants in whom there appears to be clinical jaundice that is excessive for age.^38,39

During routine clinical care, TcB measurement provides a reasonable estimate of the TSB level in healthy newborns at levels less than 15 mg/dL,⁴⁰ although TcB testing might not be available in the outpatient office. An AAP management algorithm can help determine when a newborn should be seen for outpatient follow-up based on risk of hyperbilirubinemia; higher-risk newborns should be reevaluated in 24 hours.⁹ Outpatient visual assessment of jaundice for cephalocaudal progression—in a well-lit room, with a fully undressed newborn—correlates well with TSB test results. However, visual assessment should not be used alone to screen for hyperbilirubinemia; recent studies have demonstrated that such assessment lacks clinical reliability.⁴⁰

Laboratory assessment. All bilirubin levels should be interpreted based on the newborn’s age in hours. The need for phototherapy should be based on the zone (low, low-intermediate, high-intermediate, or high, as categorized in the AAP nomogram³⁸ in which the TSB level falls. TABLE 4^38-40 provides recommendations for laboratory studies based on risk factors. Standard curves for risk stratification have been developed by the AAP.^37,38

Treatment. Decisions to initiate treatment should be based on the AAP algorithm.³⁸ When initiating phototherapy, precautions include ensuring adequate fluid intake, patching eyes, and monitoring temperature. Phototherapy can generally be stopped when the TSB level falls by 5 mg/dL or below 14 mg/dL. Home phototherapy, using a fiberoptic blanket, for uncomplicated jaundice (in carefully selected newborns with reliable parents) allows continued breastfeeding and bonding with the family, and can significantly decrease the rate of rehospitalization for infants older than 34 weeks.⁴¹

Breastfeeding is often associated with a higher bilirubin level than is seen in infants fed formula exclusively; increasing the frequency of feeding usually reduces the bilirubin level. So-called breast-milk jaundice is a delayed, but common, form of jaundice that is usually diagnosed in the second week of life and peaks by the end of the second week, resolving gradually over one to 4 months. If evaluation reveals no pathologic source, breastfeeding can generally be continued. Temporary discontinuation of breastfeeding to consider a diagnosis of breast-milk jaundice or other reasons for an elevated bilirubin level increases the risk of breastfeeding failure and is usually unnecessary.^12,37,39

Fever—a full work-up, thorough history are key

Concern about serious bacterial illness (SBI) makes the evaluation of fever critical for those who care for newborns. Many studies have attempted to identify which newborns might be able to be cared for safely as outpatients to prevent unnecessary testing and antibiotics.^5,42 Regrettably, SBI in infants remains difficult to predict, and protocols that have been developed may miss as many as 1 of every 10 newborns who has SBI.⁴³ Initial management of all infants 28 days old or younger with fever must therefore include a full work-up, including lumbar puncture and empiric antibiotics.⁴⁴

Evaluation. When an infant younger than 28 days has a fever, the physician should first verify that the temperature was taken rectally and how it was documented. In an infant who has a history of prematurity, it is crucial to correct for chronological age when deciding on proper evaluation.

Additional important findings in the history include a significant change in behavior, associated symptoms, and exposure to sick contacts. The maternal and birth history, including prolonged rupture of membranes, colonization with group B Streptococcus, administration of antibiotics at delivery, and genital herpes simplex virus (HSV) infection may suggest a cause for fever.⁴⁵

The evaluation of fever might include the white blood cell (WBC) count, blood culture, measurement of markers of inflammation, urine studies, lumbar puncture, stool culture, and chest radiograph. Traditionally, the WBC count has been utilized as a standard marker for sepsis, although it has a low sensitivity and specificity for SBI, especially in newborns.⁴⁶ Blood cultures should be obtained routinely in the newborn with fever, and before antibiotics are administered in older infants.

Procalcitonin (PCT; a calcitonin precursor) and the inflammatory marker C-reactive protein (CRP) have been shown, in several large studies, to have relatively high sensitivity and specificity for SBI; measurement of these constituents may enhance detection of serious illness.^46-49 In a large study of 2047 febrile infants older than 30 months, the PCT level was determined to be more accurate than the CRP level, the WBC count, and the absolute neutrophil count in predicting SBI.^48,49 PCT shows the most promise for preventing a full fever work-up and empiric antibiotics. It has not yet been widely translated into practice, however, because of a lack of clear guidance on how to combine PCT levels with other laboratory markers and clinical decision-making.^48-50

Urinalysis (UA) should be obtained for all newborns who present with fever. Traditionally, it was recommended that urine should be cultured for all newborns with fever; however, more recent data show that the initial urinalysis is much more sensitive than once thought. In a study, UA was positive (defined as pyuria or a positive leukocyte esterase test, or both) in all but 1 of 203 infants who had bacteremic UTI (sensitivity, 99.5%).⁵¹

The procalcitonin level was determined to be more accurate than the C-reactive protein level, the white blood cell count, and the absolute neutrophil count in predicting serious bacterial illness.

Stool culture is necessary in newborns only when they present with blood or mucus in diarrhea. Lumbar puncture should be performed in all febrile newborns and all newborns for whom empiric antibiotics have been prescribed.^43,44 A chest radiograph may be useful in diagnosis when a newborn has any other sign of pulmonary disease: respiratory rate >50/min, retractions, wheezing, grunting, stridor, nasal flaring, cough, and positive findings on lung examination.^43,44

Treatment. Management for all newborns who have a rectal temperature ≥38° C includes admission to the hospital and empiric antibiotics; guidance is based primarily on expert consensus. Common pathogens for SBI include group B Strep, Escherichia coli, Enterococcus spp., and Listeria monocytogenes.^43,44 Empiric antibiotics, including ampicillin (to cover L monocytogenes) and cefotaxime or gentamicin should be started immediately after sending for blood, urine, and cerebrospinal fluid (CSF) cultures.^43-45

Management for all newborns who have rectal temperature ≥38° C includes admission to the hospital and empiric antibiotics.

All infants who are ill-appearing or have vesicles, seizures, or a maternal history of genital HSV infection should also be started on empiric acyclovir. Vesicles should be cultured and CSF should be sent for HSV DNA polymerase chain reaction before acyclovir is administered.^43-45

Sudden infant death syndrome: Steps to take to minimize risk

SIDS is defined as the sudden death of a child younger than 1 year that remains unexplained after a thorough case investigation and comprehensive review of the clinical history. The risk of SIDS in the United States is less than 1 for every 1000 live births; incidence peaks between 2 and 4 months of age.⁵² In the United States, SIDS and other sleep-related infant deaths, such as strangulation in bed or accidental suffocation, account for more than 4000 deaths a year.⁵³ The incidence of SIDS declined markedly after the “Back to Sleep” campaign was launched in 2003, but has leveled off since 2005.^53-55

Numerous risk factors for SIDS have been identified, including maternal factors (young maternal age, maternal smoking during pregnancy, late or no prenatal care) and infant and environmental factors (prematurity, low birth weight, male gender, prone sleeping position, sleeping on a soft surface or with bedding accessories, bed-sharing (ie, sleeping in the parents’ bed), and overheating. In many cases, the risk factors are modifiable; sleeping in the prone position is the most meaningful modifiable risk factor.

Home monitors have not been proven to reduce the incidence of SIDS and are not recommended for that purpose.

To minimize the risk for SIDS, parents should be educated on the risk factors—prenatally as well as at each infant well visit. Home monitors have not been proven to reduce the incidence of SIDS and are not recommended for that purpose.^54-57 Although evidence is strongest for supine positioning as a preventive intervention for SIDS, other evidence-based recommendations include use of a firm sleep surface; breastfeeding; use of a pacifier; room-sharing with parents without bed-sharing; routine immunization; avoidance of overheating; avoiding falling asleep with the infant on a chair or couch; and avoiding exposure to tobacco smoke, alcohol, and drugs of abuse.^55,56 A recent systematic review showed that large-scale community interventions and education campaigns can play a significant role in parental and community adoption of safe sleep recommendations; however, families and communities rarely exhibit complete adherence to safe sleep practices.⁵⁷

Other concerns in the first month of life and immediately beyond

In TABLE 5,² we list additional common newborn problems not reviewed in the text of this article and summarize evidence-based treatment strategies.

CORRESPONDENCE
Scott Hartman, MD, Associate Professor, Department of Family Medicine, University of Rochester Medical Center, 777 South Clinton Avenue, Rochester, NY 14620; scott_hartman@urmc.rochester.edu.

Acknowledgement
We thank Nancy Phillips for her assistance in the preparation of this article.

ILLUSTRATIVE CASE

A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that are preventing her from attending school 3 to 4 days per month. As part of her treatment regimen, you are considering migraine prevention strategies.

Should you prescribe amitriptyline or topiramate for preventive migraine therapy?

Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.² Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.^3,4 And the US Food and Drug Administration (FDA) has not approved any medications for preventing migraines in children younger than 12 years of age. However, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.^3,4

There is low-quality evidence from individual randomized controlled trials (RCTs) about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included 3 RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur <15 times/month) in a combined total of 283 children younger than 18 years of age.⁵ Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (-0.71; 95% confidence interval [CI], -1.19 to -0.24). This is based on moderate quality evidence due to a high placebo response rate and study durations of only 12 weeks.⁵ The FDA has approved topiramate for migraine prevention in children ages 12 to 17 years.⁶

Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.⁷ In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A evidence) and medium-quality evidence (Level B), respectively.⁷

[polldaddy:9973304]

 

 

STUDY SUMMARY

Both drugs are no better than placebo in children

A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.¹ Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an 8-week period based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.

Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least 4 headache days over a prospective 28-day pre-treatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (mild to moderate disability=11-50; severe disability >50).^1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days over the 28-day pre-therapy (baseline) period compared with the final 28 days of the trial.¹

The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients), respectively. After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR]=0.71; 98% CI, 0.34-1.48; P=.26 between amitriptyline and placebo; OR=0.81; 98% CI, 0.39-1.68; P=.48 between topiramate and placebo; OR=0.88; 98% CI, 0.49-1.59; P=.49 between amitriptyline and topiramate).

There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH]=8) and dry mouth (NNH=9) and was associated with 3 serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH=4) and weight loss (NNH=13) and was associated with one serious adverse event—a suicide attempt.¹

 

 

WHAT’S NEW?

Higher-level evidence demonstrates lack of efficacy

This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk of increased adverse events with topiramate and amitriptyline.

After 24 weeks of therapy, there was no significant difference between amitriptyline, topiramate, and placebo in the primary or secondary outcomes.

Two of the 3 topiramate trials used in the older meta-analysis by El-Chammas and colleagues⁵ and this new RCT¹ were included in an updated meta-analysis by Le and colleagues (total participants 465) published in 2017.² This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio = 1.26; 95% CI, 0.94-1.67) and in the overall number of headache days (mean difference = -0.77; 95% CI, -2.31 to 0.76) in patients younger than 18 years of age.² Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate vs placebo.^2,5

CAVEATS

Is there a gender predominance?

El-Chammas and colleagues⁵ describe male pediatric patients as being the predominant pediatric gender with migraines. However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study,¹ in addition to the total population of the meta-analysis by Le and colleagues,² included women as the predominant patient population. Hopefully, future studies will help to delineate if there is a gender predominance and, if so, whether the current treatment data apply to both genders.

CHALLENGES TO IMPLEMENTATION

None to speak of

There are no barriers to implementing this recommendation immediately in all primary care settings.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that are preventing her from attending school 3 to 4 days per month. As part of her treatment regimen, you are considering migraine prevention strategies.

Should you prescribe amitriptyline or topiramate for preventive migraine therapy?

Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.² Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.^3,4 And the US Food and Drug Administration (FDA) has not approved any medications for preventing migraines in children younger than 12 years of age. However, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.^3,4

There is low-quality evidence from individual randomized controlled trials (RCTs) about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included 3 RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur <15 times/month) in a combined total of 283 children younger than 18 years of age.⁵ Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (-0.71; 95% confidence interval [CI], -1.19 to -0.24). This is based on moderate quality evidence due to a high placebo response rate and study durations of only 12 weeks.⁵ The FDA has approved topiramate for migraine prevention in children ages 12 to 17 years.⁶

Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.⁷ In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A evidence) and medium-quality evidence (Level B), respectively.⁷

[polldaddy:9973304]

 

 

STUDY SUMMARY

Both drugs are no better than placebo in children

A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.¹ Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an 8-week period based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.

Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least 4 headache days over a prospective 28-day pre-treatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (mild to moderate disability=11-50; severe disability >50).^1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days over the 28-day pre-therapy (baseline) period compared with the final 28 days of the trial.¹

The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients), respectively. After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR]=0.71; 98% CI, 0.34-1.48; P=.26 between amitriptyline and placebo; OR=0.81; 98% CI, 0.39-1.68; P=.48 between topiramate and placebo; OR=0.88; 98% CI, 0.49-1.59; P=.49 between amitriptyline and topiramate).

There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH]=8) and dry mouth (NNH=9) and was associated with 3 serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH=4) and weight loss (NNH=13) and was associated with one serious adverse event—a suicide attempt.¹

 

 

WHAT’S NEW?

Higher-level evidence demonstrates lack of efficacy

This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk of increased adverse events with topiramate and amitriptyline.

After 24 weeks of therapy, there was no significant difference between amitriptyline, topiramate, and placebo in the primary or secondary outcomes.

Two of the 3 topiramate trials used in the older meta-analysis by El-Chammas and colleagues⁵ and this new RCT¹ were included in an updated meta-analysis by Le and colleagues (total participants 465) published in 2017.² This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio = 1.26; 95% CI, 0.94-1.67) and in the overall number of headache days (mean difference = -0.77; 95% CI, -2.31 to 0.76) in patients younger than 18 years of age.² Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate vs placebo.^2,5

CAVEATS

Is there a gender predominance?

El-Chammas and colleagues⁵ describe male pediatric patients as being the predominant pediatric gender with migraines. However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study,¹ in addition to the total population of the meta-analysis by Le and colleagues,² included women as the predominant patient population. Hopefully, future studies will help to delineate if there is a gender predominance and, if so, whether the current treatment data apply to both genders.

CHALLENGES TO IMPLEMENTATION

None to speak of

There are no barriers to implementing this recommendation immediately in all primary care settings.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that are preventing her from attending school 3 to 4 days per month. As part of her treatment regimen, you are considering migraine prevention strategies.

Should you prescribe amitriptyline or topiramate for preventive migraine therapy?

Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.² Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.^3,4 And the US Food and Drug Administration (FDA) has not approved any medications for preventing migraines in children younger than 12 years of age. However, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.^3,4

There is low-quality evidence from individual randomized controlled trials (RCTs) about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included 3 RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur <15 times/month) in a combined total of 283 children younger than 18 years of age.⁵ Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (-0.71; 95% confidence interval [CI], -1.19 to -0.24). This is based on moderate quality evidence due to a high placebo response rate and study durations of only 12 weeks.⁵ The FDA has approved topiramate for migraine prevention in children ages 12 to 17 years.⁶

Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.⁷ In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A evidence) and medium-quality evidence (Level B), respectively.⁷

[polldaddy:9973304]

 

 

STUDY SUMMARY

Both drugs are no better than placebo in children

A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.¹ Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an 8-week period based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.

Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least 4 headache days over a prospective 28-day pre-treatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (mild to moderate disability=11-50; severe disability >50).^1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days over the 28-day pre-therapy (baseline) period compared with the final 28 days of the trial.¹

The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients), respectively. After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR]=0.71; 98% CI, 0.34-1.48; P=.26 between amitriptyline and placebo; OR=0.81; 98% CI, 0.39-1.68; P=.48 between topiramate and placebo; OR=0.88; 98% CI, 0.49-1.59; P=.49 between amitriptyline and topiramate).

There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH]=8) and dry mouth (NNH=9) and was associated with 3 serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH=4) and weight loss (NNH=13) and was associated with one serious adverse event—a suicide attempt.¹

 

 

WHAT’S NEW?

Higher-level evidence demonstrates lack of efficacy

This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk of increased adverse events with topiramate and amitriptyline.

After 24 weeks of therapy, there was no significant difference between amitriptyline, topiramate, and placebo in the primary or secondary outcomes.

Two of the 3 topiramate trials used in the older meta-analysis by El-Chammas and colleagues⁵ and this new RCT¹ were included in an updated meta-analysis by Le and colleagues (total participants 465) published in 2017.² This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio = 1.26; 95% CI, 0.94-1.67) and in the overall number of headache days (mean difference = -0.77; 95% CI, -2.31 to 0.76) in patients younger than 18 years of age.² Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate vs placebo.^2,5

CAVEATS

Is there a gender predominance?

El-Chammas and colleagues⁵ describe male pediatric patients as being the predominant pediatric gender with migraines. However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study,¹ in addition to the total population of the meta-analysis by Le and colleagues,² included women as the predominant patient population. Hopefully, future studies will help to delineate if there is a gender predominance and, if so, whether the current treatment data apply to both genders.

CHALLENGES TO IMPLEMENTATION

None to speak of

There are no barriers to implementing this recommendation immediately in all primary care settings.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

SAN DIEGO – Following simple institutional care guidelines helped clinicians identify pediatric patients at moderate-to-severe risk of venous thromboembolism (VTE), results from a single-center study showed.

“Hospital-acquired VTE is on the rise in the pediatric population,” lead study author Emily Southard, MD, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This consists of a DVT or [pulmonary embolism] 48 hours or more after admission, or any time at the site of a central venous catheter.”

One published study found a 70% increased incidence in the pediatric population from 2001-2007 (Pediatrics 2009;124[4]:1001-8). More than half of the children in that study (63%) had at least one coexisting complex medical condition, with malignancy being the most common.

dbrunk@mdedge.com

SOURCE: Southard E et al. THSNA 2018.

SAN DIEGO – Following simple institutional care guidelines helped clinicians identify pediatric patients at moderate-to-severe risk of venous thromboembolism (VTE), results from a single-center study showed.

“Hospital-acquired VTE is on the rise in the pediatric population,” lead study author Emily Southard, MD, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This consists of a DVT or [pulmonary embolism] 48 hours or more after admission, or any time at the site of a central venous catheter.”

One published study found a 70% increased incidence in the pediatric population from 2001-2007 (Pediatrics 2009;124[4]:1001-8). More than half of the children in that study (63%) had at least one coexisting complex medical condition, with malignancy being the most common.

dbrunk@mdedge.com

SOURCE: Southard E et al. THSNA 2018.

SAN DIEGO – Following simple institutional care guidelines helped clinicians identify pediatric patients at moderate-to-severe risk of venous thromboembolism (VTE), results from a single-center study showed.

“Hospital-acquired VTE is on the rise in the pediatric population,” lead study author Emily Southard, MD, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “This consists of a DVT or [pulmonary embolism] 48 hours or more after admission, or any time at the site of a central venous catheter.”

One published study found a 70% increased incidence in the pediatric population from 2001-2007 (Pediatrics 2009;124[4]:1001-8). More than half of the children in that study (63%) had at least one coexisting complex medical condition, with malignancy being the most common.

dbrunk@mdedge.com

SOURCE: Southard E et al. THSNA 2018.

Two new workforce developments aim to increase the number of addiction medicine specialists and provide new training opportunities in the subspecialty.

The American Board of Medical Specialties (ABMS) recently certified its first formal wave of addiction medicine physicians, adding 1,200 specialists to the field. Addiction medicine was first recognized as a subspecialty by ABMS in 2015, followed by the first certification exam in 2017.

While the 1,200 additional addiction medicine specialists are an improvement, many more are needed, Dr. Brennan said, adding that he is optimistic that the new addiction medicine training opportunities provided by ACGME will help achieve higher numbers.

“For addiction medicine, we’ve had fellowships for about 10 years, but the funding for those fellowships was really challenging,” Dr. Brennan said. “Once you get ACGME-accredited, it gives you the ability to partake of [Centers for Medicare & Medicaid Services] funding that funds most of the graduate medical education residency fellowship spots in the United States. ACGME is the gold standard. I think that makes us much more potentially attractive for graduating physicians who are finishing their residencies.”

The certification of new addiction specialists is welcome news, particularly in the midst of the current epidemic, added Clif Knight, MD, senior vice president for education for the American Academy of Family Physicians.

“This is really good news [especially considering], the difficulty that the country is having with so much addiction – of course opioids are in the forefront – but there are so many different types of addiction,” he said in an interview. “This is good news that the certification is available and that physicians are pursuing obtaining additional expertise and recognition in their ability to treat addictions.”

Dr. Knight expressed appreciation that the ACGME training opportunities in addiction medicine are open to doctors of various specialties, he said.

“A lot of times subspecialty fellowships are only available to one specialty,” said Dr. Knight. “In this case, it looks like they’ve been very deliberate to make this available to multiple specialties. I think that really sends an important message that this is not just one specialty that is focused on [addiction medicine], but really should be something that all specialties are engaged and involved in.”

*This article was updated on 4/2/2018.

Two new workforce developments aim to increase the number of addiction medicine specialists and provide new training opportunities in the subspecialty.

The American Board of Medical Specialties (ABMS) recently certified its first formal wave of addiction medicine physicians, adding 1,200 specialists to the field. Addiction medicine was first recognized as a subspecialty by ABMS in 2015, followed by the first certification exam in 2017.

While the 1,200 additional addiction medicine specialists are an improvement, many more are needed, Dr. Brennan said, adding that he is optimistic that the new addiction medicine training opportunities provided by ACGME will help achieve higher numbers.

“For addiction medicine, we’ve had fellowships for about 10 years, but the funding for those fellowships was really challenging,” Dr. Brennan said. “Once you get ACGME-accredited, it gives you the ability to partake of [Centers for Medicare & Medicaid Services] funding that funds most of the graduate medical education residency fellowship spots in the United States. ACGME is the gold standard. I think that makes us much more potentially attractive for graduating physicians who are finishing their residencies.”

The certification of new addiction specialists is welcome news, particularly in the midst of the current epidemic, added Clif Knight, MD, senior vice president for education for the American Academy of Family Physicians.

“This is really good news [especially considering], the difficulty that the country is having with so much addiction – of course opioids are in the forefront – but there are so many different types of addiction,” he said in an interview. “This is good news that the certification is available and that physicians are pursuing obtaining additional expertise and recognition in their ability to treat addictions.”

Dr. Knight expressed appreciation that the ACGME training opportunities in addiction medicine are open to doctors of various specialties, he said.

“A lot of times subspecialty fellowships are only available to one specialty,” said Dr. Knight. “In this case, it looks like they’ve been very deliberate to make this available to multiple specialties. I think that really sends an important message that this is not just one specialty that is focused on [addiction medicine], but really should be something that all specialties are engaged and involved in.”

*This article was updated on 4/2/2018.

Two new workforce developments aim to increase the number of addiction medicine specialists and provide new training opportunities in the subspecialty.

The American Board of Medical Specialties (ABMS) recently certified its first formal wave of addiction medicine physicians, adding 1,200 specialists to the field. Addiction medicine was first recognized as a subspecialty by ABMS in 2015, followed by the first certification exam in 2017.

While the 1,200 additional addiction medicine specialists are an improvement, many more are needed, Dr. Brennan said, adding that he is optimistic that the new addiction medicine training opportunities provided by ACGME will help achieve higher numbers.

“For addiction medicine, we’ve had fellowships for about 10 years, but the funding for those fellowships was really challenging,” Dr. Brennan said. “Once you get ACGME-accredited, it gives you the ability to partake of [Centers for Medicare & Medicaid Services] funding that funds most of the graduate medical education residency fellowship spots in the United States. ACGME is the gold standard. I think that makes us much more potentially attractive for graduating physicians who are finishing their residencies.”

The certification of new addiction specialists is welcome news, particularly in the midst of the current epidemic, added Clif Knight, MD, senior vice president for education for the American Academy of Family Physicians.

“This is really good news [especially considering], the difficulty that the country is having with so much addiction – of course opioids are in the forefront – but there are so many different types of addiction,” he said in an interview. “This is good news that the certification is available and that physicians are pursuing obtaining additional expertise and recognition in their ability to treat addictions.”

Dr. Knight expressed appreciation that the ACGME training opportunities in addiction medicine are open to doctors of various specialties, he said.

“A lot of times subspecialty fellowships are only available to one specialty,” said Dr. Knight. “In this case, it looks like they’ve been very deliberate to make this available to multiple specialties. I think that really sends an important message that this is not just one specialty that is focused on [addiction medicine], but really should be something that all specialties are engaged and involved in.”

*This article was updated on 4/2/2018.

Research Hospital

Chemotherapeutic agents have been associated with neurocognitive side effects in survivors of pediatric acute lymphoblastic leukemia (ALL).

Now, researchers have found evidence to suggest that genetics and ALL itself can increase the risk for long-term problems with attention, organization, and related neurocognitive skills.

The researchers reported these findings in JAMA Oncology.

The team evaluated patients enrolled in the Total XV St. Jude clinical trial, analyzing the cerebrospinal fluid (CSF) of 235 pediatric ALL patients treated with chemotherapy alone.

The CSF had been collected at 5 times before and during treatment (between 2000 and 2010). The analysis included neurocognitive testing and brain imaging of 138 ALL survivors who were at least 8 years old and 5 years from their cancer diagnosis.

The researchers found that, even before treatment began, some patients had proteins in their CSF that suggested injury to glial cells.

“This was a surprise,” said study author Kevin Krull, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Until now, we had not suspected that leukemia by itself or the inflammatory response to the disease may lead to changes that leave ALL survivors at risk for problems with executive functioning and processing speed later.”

Previously, researchers had assumed neurocognitive problems were a side effect of ALL therapy, particularly treatment with methotrexate.

So finding elevated biomarkers in the CSF of some patients during methotrexate treatment was not surprising, but, previously, little was known about the neurotoxic mechanism involved. The biomarkers identified were indicative of injury to neurons, axons, and glial cells.

The researchers checked patients’ CSF for 5 proteins and other biomarkers of brain cell damage related to treatment with either high-dose intravenous methotrexate or intrathecal methotrexate.

The biomarkers were present early on but changed and varied throughout treatment. For example, biomarkers of demyelination were present in some patients newly diagnosed with ALL and then decreased during treatment.

Others, including biomarkers of inflammation and neuronal damage, increased as treatment progressed.

Overall, methotrexate treatment was associated with biomarkers that signaled as much as a 70% increased risk for reduced neurocognitive functioning in long-term ALL survivors.

The researchers also looked for evidence that genetic variation might influence the susceptibility of pediatric ALL patients to methotrexate injury.

The team checked patients’ DNA for 42 gene variants known to influence drug metabolism, neurodevelopment, and oxidative stress.

The analysis identified a variant of the COMT gene that was associated with higher biomarker levels following methotrexate treatment. The gene encodes instructions for a protein involved in processing the neurotransmitter dopamine in the frontal regions of the brain.

“Dopamine is the primary neurotransmitter in executive functioning,” Dr Krull noted. “This suggests that 2 independent processes might be coming together in some patients that influence their risk for diminished executive functioning.”

“Taken together, the results suggest that survivors’ neurocognitive deficits are multifactorial and reflect a complex interaction among genetics, treatment intensity, and other factors. Monitoring CSF biomarkers and screening for genetic mediators of brain injury may help identify and intervene with survivors at risk for neurocognitive problems.”

Research Hospital

Chemotherapeutic agents have been associated with neurocognitive side effects in survivors of pediatric acute lymphoblastic leukemia (ALL).

Now, researchers have found evidence to suggest that genetics and ALL itself can increase the risk for long-term problems with attention, organization, and related neurocognitive skills.

The researchers reported these findings in JAMA Oncology.

The team evaluated patients enrolled in the Total XV St. Jude clinical trial, analyzing the cerebrospinal fluid (CSF) of 235 pediatric ALL patients treated with chemotherapy alone.

The CSF had been collected at 5 times before and during treatment (between 2000 and 2010). The analysis included neurocognitive testing and brain imaging of 138 ALL survivors who were at least 8 years old and 5 years from their cancer diagnosis.

The researchers found that, even before treatment began, some patients had proteins in their CSF that suggested injury to glial cells.

“This was a surprise,” said study author Kevin Krull, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Until now, we had not suspected that leukemia by itself or the inflammatory response to the disease may lead to changes that leave ALL survivors at risk for problems with executive functioning and processing speed later.”

Previously, researchers had assumed neurocognitive problems were a side effect of ALL therapy, particularly treatment with methotrexate.

So finding elevated biomarkers in the CSF of some patients during methotrexate treatment was not surprising, but, previously, little was known about the neurotoxic mechanism involved. The biomarkers identified were indicative of injury to neurons, axons, and glial cells.

The researchers checked patients’ CSF for 5 proteins and other biomarkers of brain cell damage related to treatment with either high-dose intravenous methotrexate or intrathecal methotrexate.

The biomarkers were present early on but changed and varied throughout treatment. For example, biomarkers of demyelination were present in some patients newly diagnosed with ALL and then decreased during treatment.

Others, including biomarkers of inflammation and neuronal damage, increased as treatment progressed.

Overall, methotrexate treatment was associated with biomarkers that signaled as much as a 70% increased risk for reduced neurocognitive functioning in long-term ALL survivors.

The researchers also looked for evidence that genetic variation might influence the susceptibility of pediatric ALL patients to methotrexate injury.

The team checked patients’ DNA for 42 gene variants known to influence drug metabolism, neurodevelopment, and oxidative stress.

The analysis identified a variant of the COMT gene that was associated with higher biomarker levels following methotrexate treatment. The gene encodes instructions for a protein involved in processing the neurotransmitter dopamine in the frontal regions of the brain.

“Dopamine is the primary neurotransmitter in executive functioning,” Dr Krull noted. “This suggests that 2 independent processes might be coming together in some patients that influence their risk for diminished executive functioning.”

“Taken together, the results suggest that survivors’ neurocognitive deficits are multifactorial and reflect a complex interaction among genetics, treatment intensity, and other factors. Monitoring CSF biomarkers and screening for genetic mediators of brain injury may help identify and intervene with survivors at risk for neurocognitive problems.”

Research Hospital

Chemotherapeutic agents have been associated with neurocognitive side effects in survivors of pediatric acute lymphoblastic leukemia (ALL).

Now, researchers have found evidence to suggest that genetics and ALL itself can increase the risk for long-term problems with attention, organization, and related neurocognitive skills.

The researchers reported these findings in JAMA Oncology.

The team evaluated patients enrolled in the Total XV St. Jude clinical trial, analyzing the cerebrospinal fluid (CSF) of 235 pediatric ALL patients treated with chemotherapy alone.

The CSF had been collected at 5 times before and during treatment (between 2000 and 2010). The analysis included neurocognitive testing and brain imaging of 138 ALL survivors who were at least 8 years old and 5 years from their cancer diagnosis.

The researchers found that, even before treatment began, some patients had proteins in their CSF that suggested injury to glial cells.

“This was a surprise,” said study author Kevin Krull, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Until now, we had not suspected that leukemia by itself or the inflammatory response to the disease may lead to changes that leave ALL survivors at risk for problems with executive functioning and processing speed later.”

Previously, researchers had assumed neurocognitive problems were a side effect of ALL therapy, particularly treatment with methotrexate.

So finding elevated biomarkers in the CSF of some patients during methotrexate treatment was not surprising, but, previously, little was known about the neurotoxic mechanism involved. The biomarkers identified were indicative of injury to neurons, axons, and glial cells.

The researchers checked patients’ CSF for 5 proteins and other biomarkers of brain cell damage related to treatment with either high-dose intravenous methotrexate or intrathecal methotrexate.

The biomarkers were present early on but changed and varied throughout treatment. For example, biomarkers of demyelination were present in some patients newly diagnosed with ALL and then decreased during treatment.

Others, including biomarkers of inflammation and neuronal damage, increased as treatment progressed.

Overall, methotrexate treatment was associated with biomarkers that signaled as much as a 70% increased risk for reduced neurocognitive functioning in long-term ALL survivors.

The researchers also looked for evidence that genetic variation might influence the susceptibility of pediatric ALL patients to methotrexate injury.

The team checked patients’ DNA for 42 gene variants known to influence drug metabolism, neurodevelopment, and oxidative stress.

The analysis identified a variant of the COMT gene that was associated with higher biomarker levels following methotrexate treatment. The gene encodes instructions for a protein involved in processing the neurotransmitter dopamine in the frontal regions of the brain.

“Dopamine is the primary neurotransmitter in executive functioning,” Dr Krull noted. “This suggests that 2 independent processes might be coming together in some patients that influence their risk for diminished executive functioning.”

“Taken together, the results suggest that survivors’ neurocognitive deficits are multifactorial and reflect a complex interaction among genetics, treatment intensity, and other factors. Monitoring CSF biomarkers and screening for genetic mediators of brain injury may help identify and intervene with survivors at risk for neurocognitive problems.”

A hospital quality improvement initiative reduced antibiotic use by more than half when well-appearing newborns exposed to chorioamnionitis were initially monitored for symptoms instead of routinely given antibiotics, found a study in Pediatrics.

“The reduction in both antibiotic use and laboratory testing occurred without clinically relevant delays in care or poor outcomes,” wrote Neha S. Joshi, MD, of Stanford (Calif.) University and her associates.

tatyana_tomsickova/Thinkstock

The researchers collected data on antibiotic use, lab tests, cultures, and clinical outcomes from the remaining 277 well-appearing newborns; 88% did not receive antibiotics during their hospital stay, and 83% underwent no laboratory testing. Only 17% of infants had lab testing for sepsis; none had culture result–positive, early-onset sepsis.

Only 12% of infants who initially appeared well developed signs/symptoms of sepsis, underwent laboratory testing, and received antibiotics. Nearly half of these (5% of all infants) received antibiotic treatment for at least 5 days despite negative cultures, while the other 7% received antibiotics for less than 48 hours, Dr. Joshi and her colleagues reported.

Infants with at least 34 weeks’ gestation receiving antibiotics at the hospital dropped from 12.3% before the initiative to 5.5% afterward, a 55% decrease (95% confidence interval, 40%-60%), the researchers said. Study limitations included a lack of postdischarge follow-up, the variability in physician decisions about which infants were symptomatic and which ones needed antibiotics, and an inability to generalize findings to institutions without 24/7 availability of neonatal hospitalists.

Past studies have found that all newborns with positive cultures showed symptoms at birth and needed resuscitation, continuous positive airway pressure, or intubation.

“An infant who is well-appearing at birth likely has an even lower risk of early-onset sepsis even in the setting of chorioamnionitis, and an empirical antibiotic treatment strategy for chorioamnionitis-exposed infants will result in a large number of uninfected infants being treated,” Dr. Joshi and her associates said. “Updated treatment approaches are needed to reduce unnecessary antibiotic exposure and provide higher-value care in this population.”

The study did not use external funding. The authors had no disclosures.

SOURCE: Joshi NS et al. Pediatrics. 2018;141(4):e20172056.

A hospital quality improvement initiative reduced antibiotic use by more than half when well-appearing newborns exposed to chorioamnionitis were initially monitored for symptoms instead of routinely given antibiotics, found a study in Pediatrics.

“The reduction in both antibiotic use and laboratory testing occurred without clinically relevant delays in care or poor outcomes,” wrote Neha S. Joshi, MD, of Stanford (Calif.) University and her associates.

tatyana_tomsickova/Thinkstock

The researchers collected data on antibiotic use, lab tests, cultures, and clinical outcomes from the remaining 277 well-appearing newborns; 88% did not receive antibiotics during their hospital stay, and 83% underwent no laboratory testing. Only 17% of infants had lab testing for sepsis; none had culture result–positive, early-onset sepsis.

Only 12% of infants who initially appeared well developed signs/symptoms of sepsis, underwent laboratory testing, and received antibiotics. Nearly half of these (5% of all infants) received antibiotic treatment for at least 5 days despite negative cultures, while the other 7% received antibiotics for less than 48 hours, Dr. Joshi and her colleagues reported.

Infants with at least 34 weeks’ gestation receiving antibiotics at the hospital dropped from 12.3% before the initiative to 5.5% afterward, a 55% decrease (95% confidence interval, 40%-60%), the researchers said. Study limitations included a lack of postdischarge follow-up, the variability in physician decisions about which infants were symptomatic and which ones needed antibiotics, and an inability to generalize findings to institutions without 24/7 availability of neonatal hospitalists.

Past studies have found that all newborns with positive cultures showed symptoms at birth and needed resuscitation, continuous positive airway pressure, or intubation.

“An infant who is well-appearing at birth likely has an even lower risk of early-onset sepsis even in the setting of chorioamnionitis, and an empirical antibiotic treatment strategy for chorioamnionitis-exposed infants will result in a large number of uninfected infants being treated,” Dr. Joshi and her associates said. “Updated treatment approaches are needed to reduce unnecessary antibiotic exposure and provide higher-value care in this population.”

The study did not use external funding. The authors had no disclosures.

SOURCE: Joshi NS et al. Pediatrics. 2018;141(4):e20172056.

A hospital quality improvement initiative reduced antibiotic use by more than half when well-appearing newborns exposed to chorioamnionitis were initially monitored for symptoms instead of routinely given antibiotics, found a study in Pediatrics.

“The reduction in both antibiotic use and laboratory testing occurred without clinically relevant delays in care or poor outcomes,” wrote Neha S. Joshi, MD, of Stanford (Calif.) University and her associates.

tatyana_tomsickova/Thinkstock

The researchers collected data on antibiotic use, lab tests, cultures, and clinical outcomes from the remaining 277 well-appearing newborns; 88% did not receive antibiotics during their hospital stay, and 83% underwent no laboratory testing. Only 17% of infants had lab testing for sepsis; none had culture result–positive, early-onset sepsis.

Only 12% of infants who initially appeared well developed signs/symptoms of sepsis, underwent laboratory testing, and received antibiotics. Nearly half of these (5% of all infants) received antibiotic treatment for at least 5 days despite negative cultures, while the other 7% received antibiotics for less than 48 hours, Dr. Joshi and her colleagues reported.

Infants with at least 34 weeks’ gestation receiving antibiotics at the hospital dropped from 12.3% before the initiative to 5.5% afterward, a 55% decrease (95% confidence interval, 40%-60%), the researchers said. Study limitations included a lack of postdischarge follow-up, the variability in physician decisions about which infants were symptomatic and which ones needed antibiotics, and an inability to generalize findings to institutions without 24/7 availability of neonatal hospitalists.

Past studies have found that all newborns with positive cultures showed symptoms at birth and needed resuscitation, continuous positive airway pressure, or intubation.

“An infant who is well-appearing at birth likely has an even lower risk of early-onset sepsis even in the setting of chorioamnionitis, and an empirical antibiotic treatment strategy for chorioamnionitis-exposed infants will result in a large number of uninfected infants being treated,” Dr. Joshi and her associates said. “Updated treatment approaches are needed to reduce unnecessary antibiotic exposure and provide higher-value care in this population.”

The study did not use external funding. The authors had no disclosures.

SOURCE: Joshi NS et al. Pediatrics. 2018;141(4):e20172056.

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).

The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.

Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.

As it is in adults, fosaprepitant would be given to children as part of combination therapy.

The CHMP’s opinion on fosaprepitant will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.

Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.

Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).

The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.

Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.

As it is in adults, fosaprepitant would be given to children as part of combination therapy.

The CHMP’s opinion on fosaprepitant will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.

Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.

Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).

The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.

Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.

As it is in adults, fosaprepitant would be given to children as part of combination therapy.

The CHMP’s opinion on fosaprepitant will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

The EC typically makes a decision within 67 days of the CHMP’s recommendation.

Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.

Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.

Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).

Clinically important traumatic brain injury (ciTBI) is uncommon in children with minor head injuries associated with isolated vomiting, said Meredith L. Borland, MD, of the Princess Margaret Hospital for Children, Perth, Australia, and her associates.

Likewise, traumatic brain injury evident on computed tomography (TBI-CT) is rare in such cases.

In a study published in Pediatrics, 19,920 eligible children younger than 18 years were enrolled in the Australasian Paediatric Head Injury Rule Study (APHIRST); 3,389 had a history of any vomiting, and 1,006 had isolated vomiting without any other clinical decision rules predictors. Results found 76 of the 172 (44%) children with a ciTBI and 123 of the 285 (43%) children with TBI-CT had any history of vomiting. When the Children’s Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) rule predictors for those with isolated vomiting – both fewer than three times (n = 662 of 1,006; 66%) and also three or more times (n = 344 of 1,006; 34%) – was applied, there was only one child with ciTBI, and there were only two children with a TBI-CT.

Within the subsample comprising 457 children younger than 2 years old with isolated vomiting out of the overall 1,006 (45%), there were none with ciTBI or TBI-CT. In the 549 (55%) children 2 years old and older with isolated vomiting, one (0.3%) had ciTBI, and two (0.6%) had TBI-CT.

In multivariate regression, signs of skull fracture, altered mental status, headache, and acting abnormally were significantly associated with ciTBI. Signs of a skull fracture, nonaccidental injury concern, headache, and acting abnormally were significantly associated with TBI-CT.

“TBI-CT is uncommon, and ciTBI is uncommon in children with minor blunt head injury when vomiting is their only sign or symptom,” Dr. Borland and her associates concluded. “In children with isolated vomiting, strategies such as observation should be considered before conducting an immediate CT scan.”

Read the full study in Pediatrics.
 

llaubach@mdedge.com

Clinically important traumatic brain injury (ciTBI) is uncommon in children with minor head injuries associated with isolated vomiting, said Meredith L. Borland, MD, of the Princess Margaret Hospital for Children, Perth, Australia, and her associates.

Likewise, traumatic brain injury evident on computed tomography (TBI-CT) is rare in such cases.

In a study published in Pediatrics, 19,920 eligible children younger than 18 years were enrolled in the Australasian Paediatric Head Injury Rule Study (APHIRST); 3,389 had a history of any vomiting, and 1,006 had isolated vomiting without any other clinical decision rules predictors. Results found 76 of the 172 (44%) children with a ciTBI and 123 of the 285 (43%) children with TBI-CT had any history of vomiting. When the Children’s Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) rule predictors for those with isolated vomiting – both fewer than three times (n = 662 of 1,006; 66%) and also three or more times (n = 344 of 1,006; 34%) – was applied, there was only one child with ciTBI, and there were only two children with a TBI-CT.

Within the subsample comprising 457 children younger than 2 years old with isolated vomiting out of the overall 1,006 (45%), there were none with ciTBI or TBI-CT. In the 549 (55%) children 2 years old and older with isolated vomiting, one (0.3%) had ciTBI, and two (0.6%) had TBI-CT.

In multivariate regression, signs of skull fracture, altered mental status, headache, and acting abnormally were significantly associated with ciTBI. Signs of a skull fracture, nonaccidental injury concern, headache, and acting abnormally were significantly associated with TBI-CT.

“TBI-CT is uncommon, and ciTBI is uncommon in children with minor blunt head injury when vomiting is their only sign or symptom,” Dr. Borland and her associates concluded. “In children with isolated vomiting, strategies such as observation should be considered before conducting an immediate CT scan.”

Read the full study in Pediatrics.
 

llaubach@mdedge.com

Clinically important traumatic brain injury (ciTBI) is uncommon in children with minor head injuries associated with isolated vomiting, said Meredith L. Borland, MD, of the Princess Margaret Hospital for Children, Perth, Australia, and her associates.

Likewise, traumatic brain injury evident on computed tomography (TBI-CT) is rare in such cases.

In a study published in Pediatrics, 19,920 eligible children younger than 18 years were enrolled in the Australasian Paediatric Head Injury Rule Study (APHIRST); 3,389 had a history of any vomiting, and 1,006 had isolated vomiting without any other clinical decision rules predictors. Results found 76 of the 172 (44%) children with a ciTBI and 123 of the 285 (43%) children with TBI-CT had any history of vomiting. When the Children’s Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) rule predictors for those with isolated vomiting – both fewer than three times (n = 662 of 1,006; 66%) and also three or more times (n = 344 of 1,006; 34%) – was applied, there was only one child with ciTBI, and there were only two children with a TBI-CT.

Within the subsample comprising 457 children younger than 2 years old with isolated vomiting out of the overall 1,006 (45%), there were none with ciTBI or TBI-CT. In the 549 (55%) children 2 years old and older with isolated vomiting, one (0.3%) had ciTBI, and two (0.6%) had TBI-CT.

In multivariate regression, signs of skull fracture, altered mental status, headache, and acting abnormally were significantly associated with ciTBI. Signs of a skull fracture, nonaccidental injury concern, headache, and acting abnormally were significantly associated with TBI-CT.

“TBI-CT is uncommon, and ciTBI is uncommon in children with minor blunt head injury when vomiting is their only sign or symptom,” Dr. Borland and her associates concluded. “In children with isolated vomiting, strategies such as observation should be considered before conducting an immediate CT scan.”

Read the full study in Pediatrics.
 

llaubach@mdedge.com

The gun control bill passed recently in Florida is a promising step forward in helping to protect children from deadly violence in schools. While various attempts to minimize gun violence have been stalled in state legislatures, in some cases for decades, this bill, which includes funding to expand mental health services for students, highlights a simple, sustainable, and nonpolitical solution: mental health providers.

Lisa Quarfoth/Thinkstock

Dr. Appel is director of the Montefiore School Health Program, which makes primary care, mental health, dental and vision services available to almost 40,000 K-12 students in 26 school-based health centers throughout the Bronx.

*This article was updated 3/29/2018.

The gun control bill passed recently in Florida is a promising step forward in helping to protect children from deadly violence in schools. While various attempts to minimize gun violence have been stalled in state legislatures, in some cases for decades, this bill, which includes funding to expand mental health services for students, highlights a simple, sustainable, and nonpolitical solution: mental health providers.

Lisa Quarfoth/Thinkstock

Dr. Appel is director of the Montefiore School Health Program, which makes primary care, mental health, dental and vision services available to almost 40,000 K-12 students in 26 school-based health centers throughout the Bronx.

*This article was updated 3/29/2018.

The gun control bill passed recently in Florida is a promising step forward in helping to protect children from deadly violence in schools. While various attempts to minimize gun violence have been stalled in state legislatures, in some cases for decades, this bill, which includes funding to expand mental health services for students, highlights a simple, sustainable, and nonpolitical solution: mental health providers.

Lisa Quarfoth/Thinkstock

Dr. Appel is director of the Montefiore School Health Program, which makes primary care, mental health, dental and vision services available to almost 40,000 K-12 students in 26 school-based health centers throughout the Bronx.

*This article was updated 3/29/2018.

“We should not consider marijuana ‘innocent until proven guilty,’ given what we already know about the harms to adolescents,”¹ Sharon Levy, MD, chair of the American Academy of Pediatrics Committee on Substance Abuse, said in an AAP press release, speaking of the legalization of marijuana in Washington and Colorado. The press release was issued in 2015 when the AAP updated its policy on the impact of marijuana policies on youth (Pediatrics. 2015. doi: 10.1542/peds.2014-4146), reaffirming its opposition to legalization of marijuana because it contended that limited studies had been done on “medical marijuana” in adults, and that there were no published studies either on the form of marijuana or other preparations that involved children.

Marijuana is a schedule I controlled substance, so the Food and Drug Administration does not regulate marijuana edibles, resulting in poor labeling and unregulated formulations.²

HighGradeRoots/Thinkstock

Marijuana overdoses can result in cognitive and motor impairment, extreme sedation, agitation, anxiety, cardiac stress, and vomiting. High quantities of THC have been reported to cause transient psychotic symptoms such as hallucinations, delusions, and anxiety.³

Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at pdnews@MDedge.com.

References

1. “American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use,” AAP press release on Jan. 26, 2015.

2. N Engl J Med. 2015;372:989-91.

3. Methods Rep RTI Press. 2016 Nov. doi: 10.3768/rtipress.2016.op.0035.1611.

4. JAMA. 2015;313(3):241-2.

5. Pediatrics. 2017 Mar;139(3):e20164069.

“We should not consider marijuana ‘innocent until proven guilty,’ given what we already know about the harms to adolescents,”¹ Sharon Levy, MD, chair of the American Academy of Pediatrics Committee on Substance Abuse, said in an AAP press release, speaking of the legalization of marijuana in Washington and Colorado. The press release was issued in 2015 when the AAP updated its policy on the impact of marijuana policies on youth (Pediatrics. 2015. doi: 10.1542/peds.2014-4146), reaffirming its opposition to legalization of marijuana because it contended that limited studies had been done on “medical marijuana” in adults, and that there were no published studies either on the form of marijuana or other preparations that involved children.

Marijuana is a schedule I controlled substance, so the Food and Drug Administration does not regulate marijuana edibles, resulting in poor labeling and unregulated formulations.²

HighGradeRoots/Thinkstock

Marijuana overdoses can result in cognitive and motor impairment, extreme sedation, agitation, anxiety, cardiac stress, and vomiting. High quantities of THC have been reported to cause transient psychotic symptoms such as hallucinations, delusions, and anxiety.³

Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at pdnews@MDedge.com.

References

1. “American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use,” AAP press release on Jan. 26, 2015.

2. N Engl J Med. 2015;372:989-91.

3. Methods Rep RTI Press. 2016 Nov. doi: 10.3768/rtipress.2016.op.0035.1611.

4. JAMA. 2015;313(3):241-2.

5. Pediatrics. 2017 Mar;139(3):e20164069.

“We should not consider marijuana ‘innocent until proven guilty,’ given what we already know about the harms to adolescents,”¹ Sharon Levy, MD, chair of the American Academy of Pediatrics Committee on Substance Abuse, said in an AAP press release, speaking of the legalization of marijuana in Washington and Colorado. The press release was issued in 2015 when the AAP updated its policy on the impact of marijuana policies on youth (Pediatrics. 2015. doi: 10.1542/peds.2014-4146), reaffirming its opposition to legalization of marijuana because it contended that limited studies had been done on “medical marijuana” in adults, and that there were no published studies either on the form of marijuana or other preparations that involved children.

Marijuana is a schedule I controlled substance, so the Food and Drug Administration does not regulate marijuana edibles, resulting in poor labeling and unregulated formulations.²

HighGradeRoots/Thinkstock

Marijuana overdoses can result in cognitive and motor impairment, extreme sedation, agitation, anxiety, cardiac stress, and vomiting. High quantities of THC have been reported to cause transient psychotic symptoms such as hallucinations, delusions, and anxiety.³

Dr. Pearce is a pediatrician in Frankfort, Ill. She said she had no relevant financial disclosures. Email her at pdnews@MDedge.com.

References

1. “American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use,” AAP press release on Jan. 26, 2015.

2. N Engl J Med. 2015;372:989-91.

3. Methods Rep RTI Press. 2016 Nov. doi: 10.3768/rtipress.2016.op.0035.1611.

4. JAMA. 2015;313(3):241-2.

5. Pediatrics. 2017 Mar;139(3):e20164069.