Leonora Kaufmann, MLIS

Evidence summary

Multiple cohort studies demonstrate that the expected events of normal labor form a bell-shaped curve. The range of labor experiences makes predicting when a particular woman will enter active labor difficult.

When does latent labor become active labor?

The first stage of labor includes latent and active phases. The latent phase is defined as the period between onset of labor and cervical dilatation of 3 to 4 cm or the time between onset of regular contractions and escalation in the rate of cervical dilation. Regular contractions must be intense, last 60 seconds, and occur in a predictable pattern. Escalating cervical dilation is marked by a change in the cervical examination over a short period of time (usually 2 hours).¹

The World Health Organization defines active labor as cervical dilation between 4 and 9 cm, with dilation usually occurring at 1 cm per hour or faster and accompanied by the beginning of fetal descent.²

Latent labor was initially described in a large prospective cohort of 10,293 term gravidas (including 4175 nulliparas and 5599 multiparas) followed from presentation to delivery.¹ Cervical dilation was assessed by examination every 30 to 120 minutes, almost always performed by the same examiner throughout labor. In primigravidas, latent labor averaged 6.4 hours, with 95% of women completing the latent phase in 20.6 hours. In multigravidas, the mean duration of latent labor was 4.8 hours, with 95% of women transitioning to active labor in 13.6 hours.

Shorter intercontraction interval linked to active labor

A recently published cohort study of women presenting to labor and delivery found that a relative decrease in the intercontraction interval was associated with a diagnosis of labor (odds ratio=1.42; 95% confidence interval, 1.06-1.90). The study failed to define either active labor or decrease in the intercontraction interval.³

Earlier admission leads to more interventions and poorer outcomes

Many studies have suggested that admitting women to the hospital during the latent phase of labor is associated with more interventions and poorer outcomes. Two large retrospective cohort studies (N=2697 and 3220) found increased rates of cesarean section in women admitted during the latent phase.^4,5 They also reported increased use of oxytocin, epidural analgesia, intrauterine pressure catheters, and fetal scalp electrodes, and increased rates of chorioamnionitis, postpartum infection, and neonatal intubation.^4,5 See the TABLE for a summary of the effects of latent-phase admission.

TABLE
Consequences of hospital admission during latent vs active labor

Labor assessment program reduced time in the labor ward

Labor assessment programs attempt to delay admission during early active labor. One randomized clinical trial (N=209) among low-risk women with reassuring maternal and fetal assessments in early labor divided the women into 2 groups when they presented for labor and delivery. One group received advice, encouragement, and support along with instructions to walk or return home and come back when labor became more active (defined as regular, painful contractions and dilation of at least 3 cm). The other group was admitted directly to the labor and delivery ward. The study found that early labor assessment decreased use of analgesics and oxytocin and reduced time spent in the labor ward.⁶

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) acknowledges in patient education literature that distinguishing true from false labor is difficult. ACOG lists characteristics of each and recommend that a woman monitor the frequency of contractions for an hour and call the doctor’s office or hospital if she thinks she’s in labor.⁷

Similarly, a patient handout from the American College of Nurse-Midwives recommends calling the health care provider if contractions are ≤5 minutes apart for more than 1 hour, several contractions are so painful that the woman cannot walk or talk, or her water breaks.⁸

A standard textbook describes normal uterine contractions during active labor as occurring every 2 to 5 minutes, and as often as every 2 to 3 minutes.⁹

Evidence summary

Multiple cohort studies demonstrate that the expected events of normal labor form a bell-shaped curve. The range of labor experiences makes predicting when a particular woman will enter active labor difficult.

When does latent labor become active labor?

The first stage of labor includes latent and active phases. The latent phase is defined as the period between onset of labor and cervical dilatation of 3 to 4 cm or the time between onset of regular contractions and escalation in the rate of cervical dilation. Regular contractions must be intense, last 60 seconds, and occur in a predictable pattern. Escalating cervical dilation is marked by a change in the cervical examination over a short period of time (usually 2 hours).¹

The World Health Organization defines active labor as cervical dilation between 4 and 9 cm, with dilation usually occurring at 1 cm per hour or faster and accompanied by the beginning of fetal descent.²

Latent labor was initially described in a large prospective cohort of 10,293 term gravidas (including 4175 nulliparas and 5599 multiparas) followed from presentation to delivery.¹ Cervical dilation was assessed by examination every 30 to 120 minutes, almost always performed by the same examiner throughout labor. In primigravidas, latent labor averaged 6.4 hours, with 95% of women completing the latent phase in 20.6 hours. In multigravidas, the mean duration of latent labor was 4.8 hours, with 95% of women transitioning to active labor in 13.6 hours.

Shorter intercontraction interval linked to active labor

A recently published cohort study of women presenting to labor and delivery found that a relative decrease in the intercontraction interval was associated with a diagnosis of labor (odds ratio=1.42; 95% confidence interval, 1.06-1.90). The study failed to define either active labor or decrease in the intercontraction interval.³

Earlier admission leads to more interventions and poorer outcomes

Many studies have suggested that admitting women to the hospital during the latent phase of labor is associated with more interventions and poorer outcomes. Two large retrospective cohort studies (N=2697 and 3220) found increased rates of cesarean section in women admitted during the latent phase.^4,5 They also reported increased use of oxytocin, epidural analgesia, intrauterine pressure catheters, and fetal scalp electrodes, and increased rates of chorioamnionitis, postpartum infection, and neonatal intubation.^4,5 See the TABLE for a summary of the effects of latent-phase admission.

TABLE
Consequences of hospital admission during latent vs active labor

Labor assessment program reduced time in the labor ward

Labor assessment programs attempt to delay admission during early active labor. One randomized clinical trial (N=209) among low-risk women with reassuring maternal and fetal assessments in early labor divided the women into 2 groups when they presented for labor and delivery. One group received advice, encouragement, and support along with instructions to walk or return home and come back when labor became more active (defined as regular, painful contractions and dilation of at least 3 cm). The other group was admitted directly to the labor and delivery ward. The study found that early labor assessment decreased use of analgesics and oxytocin and reduced time spent in the labor ward.⁶

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) acknowledges in patient education literature that distinguishing true from false labor is difficult. ACOG lists characteristics of each and recommend that a woman monitor the frequency of contractions for an hour and call the doctor’s office or hospital if she thinks she’s in labor.⁷

Similarly, a patient handout from the American College of Nurse-Midwives recommends calling the health care provider if contractions are ≤5 minutes apart for more than 1 hour, several contractions are so painful that the woman cannot walk or talk, or her water breaks.⁸

A standard textbook describes normal uterine contractions during active labor as occurring every 2 to 5 minutes, and as often as every 2 to 3 minutes.⁹

Evidence summary

Multiple cohort studies demonstrate that the expected events of normal labor form a bell-shaped curve. The range of labor experiences makes predicting when a particular woman will enter active labor difficult.

When does latent labor become active labor?

The first stage of labor includes latent and active phases. The latent phase is defined as the period between onset of labor and cervical dilatation of 3 to 4 cm or the time between onset of regular contractions and escalation in the rate of cervical dilation. Regular contractions must be intense, last 60 seconds, and occur in a predictable pattern. Escalating cervical dilation is marked by a change in the cervical examination over a short period of time (usually 2 hours).¹

The World Health Organization defines active labor as cervical dilation between 4 and 9 cm, with dilation usually occurring at 1 cm per hour or faster and accompanied by the beginning of fetal descent.²

Latent labor was initially described in a large prospective cohort of 10,293 term gravidas (including 4175 nulliparas and 5599 multiparas) followed from presentation to delivery.¹ Cervical dilation was assessed by examination every 30 to 120 minutes, almost always performed by the same examiner throughout labor. In primigravidas, latent labor averaged 6.4 hours, with 95% of women completing the latent phase in 20.6 hours. In multigravidas, the mean duration of latent labor was 4.8 hours, with 95% of women transitioning to active labor in 13.6 hours.

Shorter intercontraction interval linked to active labor

A recently published cohort study of women presenting to labor and delivery found that a relative decrease in the intercontraction interval was associated with a diagnosis of labor (odds ratio=1.42; 95% confidence interval, 1.06-1.90). The study failed to define either active labor or decrease in the intercontraction interval.³

Earlier admission leads to more interventions and poorer outcomes

Many studies have suggested that admitting women to the hospital during the latent phase of labor is associated with more interventions and poorer outcomes. Two large retrospective cohort studies (N=2697 and 3220) found increased rates of cesarean section in women admitted during the latent phase.^4,5 They also reported increased use of oxytocin, epidural analgesia, intrauterine pressure catheters, and fetal scalp electrodes, and increased rates of chorioamnionitis, postpartum infection, and neonatal intubation.^4,5 See the TABLE for a summary of the effects of latent-phase admission.

TABLE
Consequences of hospital admission during latent vs active labor

Labor assessment program reduced time in the labor ward

Labor assessment programs attempt to delay admission during early active labor. One randomized clinical trial (N=209) among low-risk women with reassuring maternal and fetal assessments in early labor divided the women into 2 groups when they presented for labor and delivery. One group received advice, encouragement, and support along with instructions to walk or return home and come back when labor became more active (defined as regular, painful contractions and dilation of at least 3 cm). The other group was admitted directly to the labor and delivery ward. The study found that early labor assessment decreased use of analgesics and oxytocin and reduced time spent in the labor ward.⁶

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) acknowledges in patient education literature that distinguishing true from false labor is difficult. ACOG lists characteristics of each and recommend that a woman monitor the frequency of contractions for an hour and call the doctor’s office or hospital if she thinks she’s in labor.⁷

Similarly, a patient handout from the American College of Nurse-Midwives recommends calling the health care provider if contractions are ≤5 minutes apart for more than 1 hour, several contractions are so painful that the woman cannot walk or talk, or her water breaks.⁸

A standard textbook describes normal uterine contractions during active labor as occurring every 2 to 5 minutes, and as often as every 2 to 3 minutes.⁹

Evidence summary

The prevalence of infertility in the US is approximately 15% to 17%.^2,3 Secondary infertility may comprise 80% of these cases, though reports vary.² Begin the evaluation of secondary infertility with a thorough history and physical, as outlined in the TABLE), followed by semen analysis and evaluation of ovulation.^1,3,4

TABLE
Secondary infertility? Here’s what to cover in the history and exam

Evaluate the male partner for varicoceles

The semen sample can be taken after the patient abstains from ejaculation for 2 to 6 days. Analyze the sample for volume, pH, sperm concentration, motility, and total number. If the sample is abnormal, repeat the analysis within 3 months.^1,5

Evaluate the male for varicoceles. A retrospective chart review compared 285 men with secondary infertility with 285 men with primary infertility. Varicoceles were the cause of secondary infertility in 177 (69%) of men with secondary infertility compared with 128 (50%) of men with primary infertility (P<.0001).⁶

Order tests to evaluate ovulation

To evaluate ovulation, look at menstrual history, serum progesterone, and urine luteinizing hormone (LH).^1,3,4 If the woman has signs of androgenic dysfunction, draw tests for LH, thyroid-stimulating hormone, follicle-stimulating hormone (FSH), testosterone, prolactin, and 17-hydroxyprogesterone. A woman with irregular menses should have her LH and FSH checked.¹

A hysterosalpingogram is an effective first test in the evaluation of the uterine cavity and tubal patency.^1,7,8 If the woman has comorbidities—such as a history of pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis—then laparoscopy should be the initial test.^1,3 One study demonstrated increased diagnostic yield with a combined approach of hysteroscopy and laparoscopy, in communities where the risk of pelvic infection was great.⁹

Routine postcoital testing is unnecessary.¹⁰ A randomized controlled trial compared 227 couples who received the postcoital test with 217 couples who did not. Routine use of the postcoital test led to more tests and more treatments but had no significant effect on the pregnancy rate.

Recommendations from others

According to the Royal College of Obstetricians and Gynecologists:¹

1. The use of basal body temperature charts to confirm ovulation does not reliably predict ovulation and is not recommended.
2. The routine measurement of thyroid function should not be offered.
3. Women should not be offered an endometrial biopsy to evaluate the luteal phase because there is no evidence that medical treatment of luteal phase defect improves pregnancy rates.
4. Women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis) should be offered hysterosalpingography to screen for tubal occlusion.
5. Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time.

Evidence summary

The prevalence of infertility in the US is approximately 15% to 17%.^2,3 Secondary infertility may comprise 80% of these cases, though reports vary.² Begin the evaluation of secondary infertility with a thorough history and physical, as outlined in the TABLE), followed by semen analysis and evaluation of ovulation.^1,3,4

TABLE
Secondary infertility? Here’s what to cover in the history and exam

Evaluate the male partner for varicoceles

The semen sample can be taken after the patient abstains from ejaculation for 2 to 6 days. Analyze the sample for volume, pH, sperm concentration, motility, and total number. If the sample is abnormal, repeat the analysis within 3 months.^1,5

Evaluate the male for varicoceles. A retrospective chart review compared 285 men with secondary infertility with 285 men with primary infertility. Varicoceles were the cause of secondary infertility in 177 (69%) of men with secondary infertility compared with 128 (50%) of men with primary infertility (P<.0001).⁶

Order tests to evaluate ovulation

To evaluate ovulation, look at menstrual history, serum progesterone, and urine luteinizing hormone (LH).^1,3,4 If the woman has signs of androgenic dysfunction, draw tests for LH, thyroid-stimulating hormone, follicle-stimulating hormone (FSH), testosterone, prolactin, and 17-hydroxyprogesterone. A woman with irregular menses should have her LH and FSH checked.¹

A hysterosalpingogram is an effective first test in the evaluation of the uterine cavity and tubal patency.^1,7,8 If the woman has comorbidities—such as a history of pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis—then laparoscopy should be the initial test.^1,3 One study demonstrated increased diagnostic yield with a combined approach of hysteroscopy and laparoscopy, in communities where the risk of pelvic infection was great.⁹

Routine postcoital testing is unnecessary.¹⁰ A randomized controlled trial compared 227 couples who received the postcoital test with 217 couples who did not. Routine use of the postcoital test led to more tests and more treatments but had no significant effect on the pregnancy rate.

Recommendations from others

According to the Royal College of Obstetricians and Gynecologists:¹

1. The use of basal body temperature charts to confirm ovulation does not reliably predict ovulation and is not recommended.
2. The routine measurement of thyroid function should not be offered.
3. Women should not be offered an endometrial biopsy to evaluate the luteal phase because there is no evidence that medical treatment of luteal phase defect improves pregnancy rates.
4. Women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis) should be offered hysterosalpingography to screen for tubal occlusion.
5. Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time.

Evidence summary

The prevalence of infertility in the US is approximately 15% to 17%.^2,3 Secondary infertility may comprise 80% of these cases, though reports vary.² Begin the evaluation of secondary infertility with a thorough history and physical, as outlined in the TABLE), followed by semen analysis and evaluation of ovulation.^1,3,4

TABLE
Secondary infertility? Here’s what to cover in the history and exam

Evaluate the male partner for varicoceles

The semen sample can be taken after the patient abstains from ejaculation for 2 to 6 days. Analyze the sample for volume, pH, sperm concentration, motility, and total number. If the sample is abnormal, repeat the analysis within 3 months.^1,5

Evaluate the male for varicoceles. A retrospective chart review compared 285 men with secondary infertility with 285 men with primary infertility. Varicoceles were the cause of secondary infertility in 177 (69%) of men with secondary infertility compared with 128 (50%) of men with primary infertility (P<.0001).⁶

Order tests to evaluate ovulation

To evaluate ovulation, look at menstrual history, serum progesterone, and urine luteinizing hormone (LH).^1,3,4 If the woman has signs of androgenic dysfunction, draw tests for LH, thyroid-stimulating hormone, follicle-stimulating hormone (FSH), testosterone, prolactin, and 17-hydroxyprogesterone. A woman with irregular menses should have her LH and FSH checked.¹

A hysterosalpingogram is an effective first test in the evaluation of the uterine cavity and tubal patency.^1,7,8 If the woman has comorbidities—such as a history of pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis—then laparoscopy should be the initial test.^1,3 One study demonstrated increased diagnostic yield with a combined approach of hysteroscopy and laparoscopy, in communities where the risk of pelvic infection was great.⁹

Routine postcoital testing is unnecessary.¹⁰ A randomized controlled trial compared 227 couples who received the postcoital test with 217 couples who did not. Routine use of the postcoital test led to more tests and more treatments but had no significant effect on the pregnancy rate.

Recommendations from others

According to the Royal College of Obstetricians and Gynecologists:¹

1. The use of basal body temperature charts to confirm ovulation does not reliably predict ovulation and is not recommended.
2. The routine measurement of thyroid function should not be offered.
3. Women should not be offered an endometrial biopsy to evaluate the luteal phase because there is no evidence that medical treatment of luteal phase defect improves pregnancy rates.
4. Women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis) should be offered hysterosalpingography to screen for tubal occlusion.
5. Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time.

Evidence summary

Urinary tract infections (UTIs) are common in reproductive-aged women. In lactating women, it’s important to select a therapy that is not only effective, but also safe for the breastfeeding infant. No studies in the literature address the safety or efficacy of UTI treatments in lactating women and their infants. Therefore, recommendations are extrapolated from studies of efficacy in the general population, studies of antibiotic penetration into breast milk, and effects of antibiotics given to infants directly.

How the efficacy of UTI treatments stack up

The best evidence for efficacy of UTI treatments comes from a 1999 meta-analysis of uncomplicated UTI in nonpregnant, nonlactating women.¹ They found TMP/SMX to be the most widely studied antibiotic and to have a 93% bacterial eradication rate; it was therefore used as a standard for comparison of other treatments. Nitrofurantoin and quinolones (ofloxacin, ciprofloxacin, and others) had comparable eradication rates to TMP/SMX in the same study; 7-day courses of nitrofurantoin were more efficacious than shorter ones. TMP/SMX is not recommended if the local resistance rate is more than 10% to 20%.²

Three-day therapy for uncomplicated UTI is more effective than single-dose therapy and equal to longer courses for most antibiotics.¹ A longer course (7 days) may be required for nitrofurantoin. Beta-lactams are associated with high levels of resistance and therefore not recommended in empiric treatment of UTI.²

A look at penetration into breast milk

Most of the data regarding antibiotic penetration into breast milk come from case series. One South African series measured breast milk levels of both trimethoprim and sulfamethoxazole among 50 Bantu women treated with TMP/SMX for various infections (including UTI).³ The women received 160 mg TMP and 800 mg SMX 2 or 3 times daily for up to 5 days. The average level of TMP in breast milk was 2 mcg/mL, and the level of SMX was 4.7 mcg/mL. Researchers calculated that the average breastfeeding infant would ingest only 1 mg of TMP and 2.5 mg of SMX per day. TMP/SMX is generally considered safe for infants in the absence of G6PD deficiency.

In a case series, 9 lactating mothers were given nitrofurantoin 100 mg orally every 6 hours for 1 day.⁴ On day 2, after a single 100 to 200 mg dose, drug levels in the breast milk 2 hours post-dose ranged from none (in 6 of the 9 women) to a maximum of 0.5 mcg/mL in one. Since even a very small amount of the drug may trigger a hemolytic reaction among G6PD-deficient individuals, the researchers called for caution when prescribing to mothers from high-risk populations.

A final case seriesadministered ciprofloxacin 750 mg, pefloxacin 400 mg, or ofloxacin 400 mg twice daily to 3 groups of 10 women each.⁵ Milk samples were obtained 6 times over 24 hours following the third dose of antibiotic. Maximum levels in breast milk occurred 2 hours after the dose, and were 3.79, 3.54, and 2.41 mcg/mL for ciprofloxacin, pefloxacin, and ofloxacin respectively. All 3 quinolones achieved higher concentrations in breast milk than in serum.

But are these drugs safe for children?

While TMP/SMX and nitrofurantoin are generally considered safe when given to infants and children (barring G6PD deficiency), data are mixed regarding the safety of quinolones. Ciprofloxacin’s FDA indication for pediatric patients is limited to postexposure anthrax prophylaxis due to evidence of fluoroquinolone-induced joint toxicity in animal studies.⁶ Despite this, they have been prescribed to tens of thousands of children for select scenarios such as chemotherapy-induced immuno-compromise, cystic fibrosis, complicated UTIs, and salmonella infections.⁷

A report was published summarizing safety data from the Bayer database of compassionate use of ciprofloxacin.⁸ The report indicates that 2030 treatment courses of ciprofloxacin were given to 1795 children up to age 17 for a variety of infections; only 3% were under age 5. Most patients received 21 to 40 mg/kg of ciprofloxacin per day; treatment duration was from 1 to 303 days. Arthralgia occurred in 1.5% of patients, most of whom had cystic fibrosis. Of the 31 patients affected, arthralgias resolved in 25, improved in 1, and remained unchanged in 1. (Data regarding resolution were unavailable for 4 patients.)

Recommendations from others

The American Academy of Pediatrics’ Committee on Drugsconsiders the following antibiotics typically used for UTI to be compatible with breastfeeding: ciprofloxacin, ofloxacin, nitrofurantoin (caution for infants with G6PD deficiency), and TMP/SMX.⁹

Drugs in Pregnancy and Lactation considers trimethoprim and sulfamethoxazole to be compatible with breastfeeding but cautions against sulfamethoxazole use in infants with known G6PD deficiency. The authors categorize nitrofurantoin, ciprofloxacin, and ofloxacin as “probably compatible/limited human data,” and advise caution with nitrofurantoin for infants with G6PD deficiency.¹⁰

Evidence summary

Urinary tract infections (UTIs) are common in reproductive-aged women. In lactating women, it’s important to select a therapy that is not only effective, but also safe for the breastfeeding infant. No studies in the literature address the safety or efficacy of UTI treatments in lactating women and their infants. Therefore, recommendations are extrapolated from studies of efficacy in the general population, studies of antibiotic penetration into breast milk, and effects of antibiotics given to infants directly.

How the efficacy of UTI treatments stack up

The best evidence for efficacy of UTI treatments comes from a 1999 meta-analysis of uncomplicated UTI in nonpregnant, nonlactating women.¹ They found TMP/SMX to be the most widely studied antibiotic and to have a 93% bacterial eradication rate; it was therefore used as a standard for comparison of other treatments. Nitrofurantoin and quinolones (ofloxacin, ciprofloxacin, and others) had comparable eradication rates to TMP/SMX in the same study; 7-day courses of nitrofurantoin were more efficacious than shorter ones. TMP/SMX is not recommended if the local resistance rate is more than 10% to 20%.²

Three-day therapy for uncomplicated UTI is more effective than single-dose therapy and equal to longer courses for most antibiotics.¹ A longer course (7 days) may be required for nitrofurantoin. Beta-lactams are associated with high levels of resistance and therefore not recommended in empiric treatment of UTI.²

A look at penetration into breast milk

Most of the data regarding antibiotic penetration into breast milk come from case series. One South African series measured breast milk levels of both trimethoprim and sulfamethoxazole among 50 Bantu women treated with TMP/SMX for various infections (including UTI).³ The women received 160 mg TMP and 800 mg SMX 2 or 3 times daily for up to 5 days. The average level of TMP in breast milk was 2 mcg/mL, and the level of SMX was 4.7 mcg/mL. Researchers calculated that the average breastfeeding infant would ingest only 1 mg of TMP and 2.5 mg of SMX per day. TMP/SMX is generally considered safe for infants in the absence of G6PD deficiency.

In a case series, 9 lactating mothers were given nitrofurantoin 100 mg orally every 6 hours for 1 day.⁴ On day 2, after a single 100 to 200 mg dose, drug levels in the breast milk 2 hours post-dose ranged from none (in 6 of the 9 women) to a maximum of 0.5 mcg/mL in one. Since even a very small amount of the drug may trigger a hemolytic reaction among G6PD-deficient individuals, the researchers called for caution when prescribing to mothers from high-risk populations.

A final case seriesadministered ciprofloxacin 750 mg, pefloxacin 400 mg, or ofloxacin 400 mg twice daily to 3 groups of 10 women each.⁵ Milk samples were obtained 6 times over 24 hours following the third dose of antibiotic. Maximum levels in breast milk occurred 2 hours after the dose, and were 3.79, 3.54, and 2.41 mcg/mL for ciprofloxacin, pefloxacin, and ofloxacin respectively. All 3 quinolones achieved higher concentrations in breast milk than in serum.

But are these drugs safe for children?

While TMP/SMX and nitrofurantoin are generally considered safe when given to infants and children (barring G6PD deficiency), data are mixed regarding the safety of quinolones. Ciprofloxacin’s FDA indication for pediatric patients is limited to postexposure anthrax prophylaxis due to evidence of fluoroquinolone-induced joint toxicity in animal studies.⁶ Despite this, they have been prescribed to tens of thousands of children for select scenarios such as chemotherapy-induced immuno-compromise, cystic fibrosis, complicated UTIs, and salmonella infections.⁷

A report was published summarizing safety data from the Bayer database of compassionate use of ciprofloxacin.⁸ The report indicates that 2030 treatment courses of ciprofloxacin were given to 1795 children up to age 17 for a variety of infections; only 3% were under age 5. Most patients received 21 to 40 mg/kg of ciprofloxacin per day; treatment duration was from 1 to 303 days. Arthralgia occurred in 1.5% of patients, most of whom had cystic fibrosis. Of the 31 patients affected, arthralgias resolved in 25, improved in 1, and remained unchanged in 1. (Data regarding resolution were unavailable for 4 patients.)

Recommendations from others

The American Academy of Pediatrics’ Committee on Drugsconsiders the following antibiotics typically used for UTI to be compatible with breastfeeding: ciprofloxacin, ofloxacin, nitrofurantoin (caution for infants with G6PD deficiency), and TMP/SMX.⁹

Drugs in Pregnancy and Lactation considers trimethoprim and sulfamethoxazole to be compatible with breastfeeding but cautions against sulfamethoxazole use in infants with known G6PD deficiency. The authors categorize nitrofurantoin, ciprofloxacin, and ofloxacin as “probably compatible/limited human data,” and advise caution with nitrofurantoin for infants with G6PD deficiency.¹⁰

Evidence summary

Urinary tract infections (UTIs) are common in reproductive-aged women. In lactating women, it’s important to select a therapy that is not only effective, but also safe for the breastfeeding infant. No studies in the literature address the safety or efficacy of UTI treatments in lactating women and their infants. Therefore, recommendations are extrapolated from studies of efficacy in the general population, studies of antibiotic penetration into breast milk, and effects of antibiotics given to infants directly.

How the efficacy of UTI treatments stack up

The best evidence for efficacy of UTI treatments comes from a 1999 meta-analysis of uncomplicated UTI in nonpregnant, nonlactating women.¹ They found TMP/SMX to be the most widely studied antibiotic and to have a 93% bacterial eradication rate; it was therefore used as a standard for comparison of other treatments. Nitrofurantoin and quinolones (ofloxacin, ciprofloxacin, and others) had comparable eradication rates to TMP/SMX in the same study; 7-day courses of nitrofurantoin were more efficacious than shorter ones. TMP/SMX is not recommended if the local resistance rate is more than 10% to 20%.²

Three-day therapy for uncomplicated UTI is more effective than single-dose therapy and equal to longer courses for most antibiotics.¹ A longer course (7 days) may be required for nitrofurantoin. Beta-lactams are associated with high levels of resistance and therefore not recommended in empiric treatment of UTI.²

A look at penetration into breast milk

Most of the data regarding antibiotic penetration into breast milk come from case series. One South African series measured breast milk levels of both trimethoprim and sulfamethoxazole among 50 Bantu women treated with TMP/SMX for various infections (including UTI).³ The women received 160 mg TMP and 800 mg SMX 2 or 3 times daily for up to 5 days. The average level of TMP in breast milk was 2 mcg/mL, and the level of SMX was 4.7 mcg/mL. Researchers calculated that the average breastfeeding infant would ingest only 1 mg of TMP and 2.5 mg of SMX per day. TMP/SMX is generally considered safe for infants in the absence of G6PD deficiency.

In a case series, 9 lactating mothers were given nitrofurantoin 100 mg orally every 6 hours for 1 day.⁴ On day 2, after a single 100 to 200 mg dose, drug levels in the breast milk 2 hours post-dose ranged from none (in 6 of the 9 women) to a maximum of 0.5 mcg/mL in one. Since even a very small amount of the drug may trigger a hemolytic reaction among G6PD-deficient individuals, the researchers called for caution when prescribing to mothers from high-risk populations.

A final case seriesadministered ciprofloxacin 750 mg, pefloxacin 400 mg, or ofloxacin 400 mg twice daily to 3 groups of 10 women each.⁵ Milk samples were obtained 6 times over 24 hours following the third dose of antibiotic. Maximum levels in breast milk occurred 2 hours after the dose, and were 3.79, 3.54, and 2.41 mcg/mL for ciprofloxacin, pefloxacin, and ofloxacin respectively. All 3 quinolones achieved higher concentrations in breast milk than in serum.

But are these drugs safe for children?

While TMP/SMX and nitrofurantoin are generally considered safe when given to infants and children (barring G6PD deficiency), data are mixed regarding the safety of quinolones. Ciprofloxacin’s FDA indication for pediatric patients is limited to postexposure anthrax prophylaxis due to evidence of fluoroquinolone-induced joint toxicity in animal studies.⁶ Despite this, they have been prescribed to tens of thousands of children for select scenarios such as chemotherapy-induced immuno-compromise, cystic fibrosis, complicated UTIs, and salmonella infections.⁷

A report was published summarizing safety data from the Bayer database of compassionate use of ciprofloxacin.⁸ The report indicates that 2030 treatment courses of ciprofloxacin were given to 1795 children up to age 17 for a variety of infections; only 3% were under age 5. Most patients received 21 to 40 mg/kg of ciprofloxacin per day; treatment duration was from 1 to 303 days. Arthralgia occurred in 1.5% of patients, most of whom had cystic fibrosis. Of the 31 patients affected, arthralgias resolved in 25, improved in 1, and remained unchanged in 1. (Data regarding resolution were unavailable for 4 patients.)

Recommendations from others

The American Academy of Pediatrics’ Committee on Drugsconsiders the following antibiotics typically used for UTI to be compatible with breastfeeding: ciprofloxacin, ofloxacin, nitrofurantoin (caution for infants with G6PD deficiency), and TMP/SMX.⁹

Drugs in Pregnancy and Lactation considers trimethoprim and sulfamethoxazole to be compatible with breastfeeding but cautions against sulfamethoxazole use in infants with known G6PD deficiency. The authors categorize nitrofurantoin, ciprofloxacin, and ofloxacin as “probably compatible/limited human data,” and advise caution with nitrofurantoin for infants with G6PD deficiency.¹⁰

Evidence summary

Contrary to the goals of Healthy People 2010, the rate of cesarean sections is increasing.¹ The repeat cesarean rate for low-risk women of all ages and racial groups is now 88.7%, the highest rate since the Centers for Disease Control and Prevention (CDC) began tracking the statistic in 1989. Is VBAC safe, or is a trial of labor no longer supported by the data?

The most recent Cochrane Review found that both VBAC and repeat lowtransverse cesarean section have benefits and risks associated with them; however, after reviewing the limited data, they concluded that no trial exists to adequately help women and their caregivers make an informed decision between the two.² A strong theme in the Cochrane Review, echoed in most reviews, was the absence of high-quality prospective randomized data.

In an attempt to quantify the risks of VBAC, a systematic review determined that attempted VBAC, compared with repeat low-transverse cesarean section, increased the risk of uterine rupture by 2.7 per 1000 cases (95% confidence interval [CI], 0.73–4.73).³ This additional risk rate is often quoted in VBAC reviews and was cited in the Agency for Healthcare Research and Quality evidence report; it is based on 1 prospective, nonrandomized cohort trial and 1 retrospective cohort study.^4,5

No randomized controlled trials exist for determining maternal safety of VBAC, although another recent systematic review found 2 nonrandomized prospective trials of sufficient quality to analyze. The authors concluded there were “no statistically significant differences between planned elective repeat cesarean section and planned VBAC.”⁶ Upon closer review in PubMed, one of the cited studies did not study 312 patients for VBAC outcomes as alleged; rather, it investigated patient attitudes towards VBAC.⁷

Since publication of that review, a large, multicenter, prospective, nonrandomized trial involving 33,699 patients found no significant difference between VBAC and planned cesarean for hysterectomy (0.2% vs 0.3%; odds ratio [OR]=0.77; 95% CI, 0.51–1.17), maternal death (0.02% vs 0.04%; OR=0.38; 95% CI, 0.1–1.46), and neonatal death (0.08% vs 0.05%; OR=1.82; 95% CI, 0.73–4.57).⁸ Significant associations were found for uterine rupture rates in spontaneous labor (24/6685 [0.4%] vs no cases; number needed to harm [NNH]=279) and neonatal hypoxic-ischemic encephalopathy (0.46 cases per 1000 vs no cases; NNH=2174).⁸

A retrospective Canadian cohort trial of 308,755 women also demonstrated an association of VBAC with uterine rupture(0.65% of trial-of-labor cases; OR=2.38; 95% CI, 2.12–2.67), and a trend towards higher maternal mortality in the cesarean group (1.6 per 100,000 for VBAC vs 5.6 per 100,000 for planned cesarean; OR=0.32; 95% CI, 0.07–1.47).⁹

The effect of VBAC on neonatal morbidity and mortality is unclear. In contrast to the negative larger trial,⁸ a smaller retrospective cohort of 24,529 births found a higher association of perinatal death for trial of labor (adjusted OR=11.7; 95% CI, 1.4–101.6).¹⁰ The perinatal death rate was similar to rates in nulliparous women. Regarding morbidity, one retrospective cohort trial showed VBAC was associated with an increase in neonatal sepsis (1% vs 0%; CI not given) compared with planned cesarean, but VBAC resulted in less transient tachypnea (5% vs 7%) and hyper-bilirubinemia (2% vs 6%).¹¹

Recommendations from others

Both the American College of Obstetricians and Gynecologists and the Society of Obstetricians and Gynecologists of Canada state that women with 1 previous low-transverse cesarean section should be offered a trial of labor after appropriate counseling of the risks and benefits.^12,13 Furthermore, induction with oxytocin is allowed, but the use of prostaglandins is not recommended. Based on expert opinion, both organizations encourage VBAC only in institutions staffed with surgeons and anesthesiologists immediately available to provide emergent cesarean.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and are not to be construed as official, or as reflecting the views of the US Air Force medical department or the US Air Force at large.

Evidence summary

Contrary to the goals of Healthy People 2010, the rate of cesarean sections is increasing.¹ The repeat cesarean rate for low-risk women of all ages and racial groups is now 88.7%, the highest rate since the Centers for Disease Control and Prevention (CDC) began tracking the statistic in 1989. Is VBAC safe, or is a trial of labor no longer supported by the data?

The most recent Cochrane Review found that both VBAC and repeat lowtransverse cesarean section have benefits and risks associated with them; however, after reviewing the limited data, they concluded that no trial exists to adequately help women and their caregivers make an informed decision between the two.² A strong theme in the Cochrane Review, echoed in most reviews, was the absence of high-quality prospective randomized data.

In an attempt to quantify the risks of VBAC, a systematic review determined that attempted VBAC, compared with repeat low-transverse cesarean section, increased the risk of uterine rupture by 2.7 per 1000 cases (95% confidence interval [CI], 0.73–4.73).³ This additional risk rate is often quoted in VBAC reviews and was cited in the Agency for Healthcare Research and Quality evidence report; it is based on 1 prospective, nonrandomized cohort trial and 1 retrospective cohort study.^4,5

No randomized controlled trials exist for determining maternal safety of VBAC, although another recent systematic review found 2 nonrandomized prospective trials of sufficient quality to analyze. The authors concluded there were “no statistically significant differences between planned elective repeat cesarean section and planned VBAC.”⁶ Upon closer review in PubMed, one of the cited studies did not study 312 patients for VBAC outcomes as alleged; rather, it investigated patient attitudes towards VBAC.⁷

Since publication of that review, a large, multicenter, prospective, nonrandomized trial involving 33,699 patients found no significant difference between VBAC and planned cesarean for hysterectomy (0.2% vs 0.3%; odds ratio [OR]=0.77; 95% CI, 0.51–1.17), maternal death (0.02% vs 0.04%; OR=0.38; 95% CI, 0.1–1.46), and neonatal death (0.08% vs 0.05%; OR=1.82; 95% CI, 0.73–4.57).⁸ Significant associations were found for uterine rupture rates in spontaneous labor (24/6685 [0.4%] vs no cases; number needed to harm [NNH]=279) and neonatal hypoxic-ischemic encephalopathy (0.46 cases per 1000 vs no cases; NNH=2174).⁸

A retrospective Canadian cohort trial of 308,755 women also demonstrated an association of VBAC with uterine rupture(0.65% of trial-of-labor cases; OR=2.38; 95% CI, 2.12–2.67), and a trend towards higher maternal mortality in the cesarean group (1.6 per 100,000 for VBAC vs 5.6 per 100,000 for planned cesarean; OR=0.32; 95% CI, 0.07–1.47).⁹

The effect of VBAC on neonatal morbidity and mortality is unclear. In contrast to the negative larger trial,⁸ a smaller retrospective cohort of 24,529 births found a higher association of perinatal death for trial of labor (adjusted OR=11.7; 95% CI, 1.4–101.6).¹⁰ The perinatal death rate was similar to rates in nulliparous women. Regarding morbidity, one retrospective cohort trial showed VBAC was associated with an increase in neonatal sepsis (1% vs 0%; CI not given) compared with planned cesarean, but VBAC resulted in less transient tachypnea (5% vs 7%) and hyper-bilirubinemia (2% vs 6%).¹¹

Recommendations from others

Both the American College of Obstetricians and Gynecologists and the Society of Obstetricians and Gynecologists of Canada state that women with 1 previous low-transverse cesarean section should be offered a trial of labor after appropriate counseling of the risks and benefits.^12,13 Furthermore, induction with oxytocin is allowed, but the use of prostaglandins is not recommended. Based on expert opinion, both organizations encourage VBAC only in institutions staffed with surgeons and anesthesiologists immediately available to provide emergent cesarean.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and are not to be construed as official, or as reflecting the views of the US Air Force medical department or the US Air Force at large.

Evidence summary

Contrary to the goals of Healthy People 2010, the rate of cesarean sections is increasing.¹ The repeat cesarean rate for low-risk women of all ages and racial groups is now 88.7%, the highest rate since the Centers for Disease Control and Prevention (CDC) began tracking the statistic in 1989. Is VBAC safe, or is a trial of labor no longer supported by the data?

The most recent Cochrane Review found that both VBAC and repeat lowtransverse cesarean section have benefits and risks associated with them; however, after reviewing the limited data, they concluded that no trial exists to adequately help women and their caregivers make an informed decision between the two.² A strong theme in the Cochrane Review, echoed in most reviews, was the absence of high-quality prospective randomized data.

In an attempt to quantify the risks of VBAC, a systematic review determined that attempted VBAC, compared with repeat low-transverse cesarean section, increased the risk of uterine rupture by 2.7 per 1000 cases (95% confidence interval [CI], 0.73–4.73).³ This additional risk rate is often quoted in VBAC reviews and was cited in the Agency for Healthcare Research and Quality evidence report; it is based on 1 prospective, nonrandomized cohort trial and 1 retrospective cohort study.^4,5

No randomized controlled trials exist for determining maternal safety of VBAC, although another recent systematic review found 2 nonrandomized prospective trials of sufficient quality to analyze. The authors concluded there were “no statistically significant differences between planned elective repeat cesarean section and planned VBAC.”⁶ Upon closer review in PubMed, one of the cited studies did not study 312 patients for VBAC outcomes as alleged; rather, it investigated patient attitudes towards VBAC.⁷

Since publication of that review, a large, multicenter, prospective, nonrandomized trial involving 33,699 patients found no significant difference between VBAC and planned cesarean for hysterectomy (0.2% vs 0.3%; odds ratio [OR]=0.77; 95% CI, 0.51–1.17), maternal death (0.02% vs 0.04%; OR=0.38; 95% CI, 0.1–1.46), and neonatal death (0.08% vs 0.05%; OR=1.82; 95% CI, 0.73–4.57).⁸ Significant associations were found for uterine rupture rates in spontaneous labor (24/6685 [0.4%] vs no cases; number needed to harm [NNH]=279) and neonatal hypoxic-ischemic encephalopathy (0.46 cases per 1000 vs no cases; NNH=2174).⁸

A retrospective Canadian cohort trial of 308,755 women also demonstrated an association of VBAC with uterine rupture(0.65% of trial-of-labor cases; OR=2.38; 95% CI, 2.12–2.67), and a trend towards higher maternal mortality in the cesarean group (1.6 per 100,000 for VBAC vs 5.6 per 100,000 for planned cesarean; OR=0.32; 95% CI, 0.07–1.47).⁹

The effect of VBAC on neonatal morbidity and mortality is unclear. In contrast to the negative larger trial,⁸ a smaller retrospective cohort of 24,529 births found a higher association of perinatal death for trial of labor (adjusted OR=11.7; 95% CI, 1.4–101.6).¹⁰ The perinatal death rate was similar to rates in nulliparous women. Regarding morbidity, one retrospective cohort trial showed VBAC was associated with an increase in neonatal sepsis (1% vs 0%; CI not given) compared with planned cesarean, but VBAC resulted in less transient tachypnea (5% vs 7%) and hyper-bilirubinemia (2% vs 6%).¹¹

Recommendations from others

Both the American College of Obstetricians and Gynecologists and the Society of Obstetricians and Gynecologists of Canada state that women with 1 previous low-transverse cesarean section should be offered a trial of labor after appropriate counseling of the risks and benefits.^12,13 Furthermore, induction with oxytocin is allowed, but the use of prostaglandins is not recommended. Based on expert opinion, both organizations encourage VBAC only in institutions staffed with surgeons and anesthesiologists immediately available to provide emergent cesarean.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and are not to be construed as official, or as reflecting the views of the US Air Force medical department or the US Air Force at large.