Fetal exposure to depression: How does ‘dose’ figure in?

 

The last two decades have seen an ever-growing number of reports on risks of fetal exposure to medicines used to treat depression during pregnancy. These reports have described issues ranging from estimated risk of congenital malformations following fetal exposure to various psychotropics such as SSRIs or atypical antipsychotics to adverse neonatal effects such as poor neonatal adaptation syndrome. More recent reports, derived primarily from large administrative databases, have focused on concerns regarding both risk for later childhood psychopathology such as autism or ADHD or neurobehavioral sequelae such as motor or speech delay following fetal exposure to antidepressants.

When considering the potential risks of fetal exposure to antidepressants on the spectrum of relevant outcomes, it is important to keep in mind the risks of not receiving antidepressant treatment. Data on known risks of antidepressant use during pregnancy are well described, but the literature supporting adverse effects of untreated depression during pregnancy has also grown substantially. For example, accumulated data over the last several years supports heightened risk for obstetrical and neonatal complications among women who suffer from untreated depression and recent data is inconclusive regarding the effects of untreated maternal depression on gene expression in the CNS during gestation and the effects of depression during pregnancy on development of actual brain structures in areas of the brain that modulate emotion and behavior.

monkeybusinessimages/Thinkstock

In my opinion, one of the greatest recent advances in perinatal psychiatry has been the increased appreciation of the effect that perinatal psychiatric illness has on critical obstetrical and neonatal outcomes, as well as risk for later child psychopathology. However, few studies, to date, have systematically examined whether duration of the exposure to perinatal psychiatric illness (or the severity of the illness) is a relevant concern.

The ability to factor “dose and duration” of exposure to perinatal psychiatric illness into a model predicting risk for a number of obstetrical or neonatal outcomes allows for a more refined risk-benefit decision with respect to use of antidepressants during pregnancy. For example, there may be a threshold over which it’s even more imperative to treat depression during pregnancy than in women who do not suffer from such severe histories of psychiatric disorder.

Research along these lines has been published in a study in Nursing Research in which the question of the effect of maternal mood on infant outcomes was examined, specifically looking at stress, depression, and intimate partner violence, and not just the presence of these elements, but their duration and intensity both before and during the pregnancy (2015 Sep-Oct;64[5]:331-41).

To do this, researchers examined survey data from Utah’s Pregnancy Risk Assessment Monitoring System of 4,296 women who gave birth during 2009-2011. Stress, depression, and intimate partner violence, and the duration and severity of each, were determined by questionnaire. Those determinations were compared with the outcomes of gestational age, birth weight, neonatal ICU admission, and the symptoms and diagnosis of postpartum depression.

Results of the study included the following: Increased duration of depression was associated with a greater risk of neonatal ICU admission, particularly in women who were depressed both before and during their pregnancy (adjusted odds ratio, 2.48), compared with women who had no depression.

 

We’ve known for a long time that a history of depression predicts increased risk for postpartum depression. In this particular study, it was actually shown that not just a history of depression, but the duration of experienced depression influenced the risk for postpartum depression.

For example, compared with women with no depression, women who were depressed before but not during their pregnancy had an aOR of 7.67, women depressed during pregnancy but not before had an aOR of 17.65, and women depressed both before and during pregnancy had an aOR of 58.35 – an extraordinary stratification of risk, basically.

What these data begin to suggest is that there may be a continuum of risk when it comes to the effects of exposure to depression (factoring in now dose and duration of exposure) during pregnancy. If risk of adverse outcome increases with greater severity of perinatal psychiatric illness, then a mandate to treat depression during pregnancy, whether with pharmacologic or nonpharmacologic interventions (or, commonly, a combination of the two) becomes that much more imperative. Regardless of the treatment interventions that are used, the importance of treating depression during pregnancy and keeping women well before, during, and after pregnancy is so critical. Such a recommendation dovetails with the literature showing the intergenerational effects of untreated depression. Maternal depression is one of the strongest predictors of later childhood psychopathology. With current national trends moving toward mandating screening initiatives for postpartum depression, the appreciation of the extent to which depression before and during pregnancy drives risk for postpartum mood disorder broadens how we think about mitigating risk for puerperal mood disturbance. Specifically, mitigating the effects of postpartum depression on women, their children, and their families must include more effective management of depression both before and during pregnancy.

 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

 

The last two decades have seen an ever-growing number of reports on risks of fetal exposure to medicines used to treat depression during pregnancy. These reports have described issues ranging from estimated risk of congenital malformations following fetal exposure to various psychotropics such as SSRIs or atypical antipsychotics to adverse neonatal effects such as poor neonatal adaptation syndrome. More recent reports, derived primarily from large administrative databases, have focused on concerns regarding both risk for later childhood psychopathology such as autism or ADHD or neurobehavioral sequelae such as motor or speech delay following fetal exposure to antidepressants.

When considering the potential risks of fetal exposure to antidepressants on the spectrum of relevant outcomes, it is important to keep in mind the risks of not receiving antidepressant treatment. Data on known risks of antidepressant use during pregnancy are well described, but the literature supporting adverse effects of untreated depression during pregnancy has also grown substantially. For example, accumulated data over the last several years supports heightened risk for obstetrical and neonatal complications among women who suffer from untreated depression and recent data is inconclusive regarding the effects of untreated maternal depression on gene expression in the CNS during gestation and the effects of depression during pregnancy on development of actual brain structures in areas of the brain that modulate emotion and behavior.

monkeybusinessimages/Thinkstock

In my opinion, one of the greatest recent advances in perinatal psychiatry has been the increased appreciation of the effect that perinatal psychiatric illness has on critical obstetrical and neonatal outcomes, as well as risk for later child psychopathology. However, few studies, to date, have systematically examined whether duration of the exposure to perinatal psychiatric illness (or the severity of the illness) is a relevant concern.

The ability to factor “dose and duration” of exposure to perinatal psychiatric illness into a model predicting risk for a number of obstetrical or neonatal outcomes allows for a more refined risk-benefit decision with respect to use of antidepressants during pregnancy. For example, there may be a threshold over which it’s even more imperative to treat depression during pregnancy than in women who do not suffer from such severe histories of psychiatric disorder.

Research along these lines has been published in a study in Nursing Research in which the question of the effect of maternal mood on infant outcomes was examined, specifically looking at stress, depression, and intimate partner violence, and not just the presence of these elements, but their duration and intensity both before and during the pregnancy (2015 Sep-Oct;64[5]:331-41).

To do this, researchers examined survey data from Utah’s Pregnancy Risk Assessment Monitoring System of 4,296 women who gave birth during 2009-2011. Stress, depression, and intimate partner violence, and the duration and severity of each, were determined by questionnaire. Those determinations were compared with the outcomes of gestational age, birth weight, neonatal ICU admission, and the symptoms and diagnosis of postpartum depression.

Results of the study included the following: Increased duration of depression was associated with a greater risk of neonatal ICU admission, particularly in women who were depressed both before and during their pregnancy (adjusted odds ratio, 2.48), compared with women who had no depression.

 

We’ve known for a long time that a history of depression predicts increased risk for postpartum depression. In this particular study, it was actually shown that not just a history of depression, but the duration of experienced depression influenced the risk for postpartum depression.

For example, compared with women with no depression, women who were depressed before but not during their pregnancy had an aOR of 7.67, women depressed during pregnancy but not before had an aOR of 17.65, and women depressed both before and during pregnancy had an aOR of 58.35 – an extraordinary stratification of risk, basically.

What these data begin to suggest is that there may be a continuum of risk when it comes to the effects of exposure to depression (factoring in now dose and duration of exposure) during pregnancy. If risk of adverse outcome increases with greater severity of perinatal psychiatric illness, then a mandate to treat depression during pregnancy, whether with pharmacologic or nonpharmacologic interventions (or, commonly, a combination of the two) becomes that much more imperative. Regardless of the treatment interventions that are used, the importance of treating depression during pregnancy and keeping women well before, during, and after pregnancy is so critical. Such a recommendation dovetails with the literature showing the intergenerational effects of untreated depression. Maternal depression is one of the strongest predictors of later childhood psychopathology. With current national trends moving toward mandating screening initiatives for postpartum depression, the appreciation of the extent to which depression before and during pregnancy drives risk for postpartum mood disorder broadens how we think about mitigating risk for puerperal mood disturbance. Specifically, mitigating the effects of postpartum depression on women, their children, and their families must include more effective management of depression both before and during pregnancy.

 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.

 

The last two decades have seen an ever-growing number of reports on risks of fetal exposure to medicines used to treat depression during pregnancy. These reports have described issues ranging from estimated risk of congenital malformations following fetal exposure to various psychotropics such as SSRIs or atypical antipsychotics to adverse neonatal effects such as poor neonatal adaptation syndrome. More recent reports, derived primarily from large administrative databases, have focused on concerns regarding both risk for later childhood psychopathology such as autism or ADHD or neurobehavioral sequelae such as motor or speech delay following fetal exposure to antidepressants.

When considering the potential risks of fetal exposure to antidepressants on the spectrum of relevant outcomes, it is important to keep in mind the risks of not receiving antidepressant treatment. Data on known risks of antidepressant use during pregnancy are well described, but the literature supporting adverse effects of untreated depression during pregnancy has also grown substantially. For example, accumulated data over the last several years supports heightened risk for obstetrical and neonatal complications among women who suffer from untreated depression and recent data is inconclusive regarding the effects of untreated maternal depression on gene expression in the CNS during gestation and the effects of depression during pregnancy on development of actual brain structures in areas of the brain that modulate emotion and behavior.

monkeybusinessimages/Thinkstock

In my opinion, one of the greatest recent advances in perinatal psychiatry has been the increased appreciation of the effect that perinatal psychiatric illness has on critical obstetrical and neonatal outcomes, as well as risk for later child psychopathology. However, few studies, to date, have systematically examined whether duration of the exposure to perinatal psychiatric illness (or the severity of the illness) is a relevant concern.

The ability to factor “dose and duration” of exposure to perinatal psychiatric illness into a model predicting risk for a number of obstetrical or neonatal outcomes allows for a more refined risk-benefit decision with respect to use of antidepressants during pregnancy. For example, there may be a threshold over which it’s even more imperative to treat depression during pregnancy than in women who do not suffer from such severe histories of psychiatric disorder.

Research along these lines has been published in a study in Nursing Research in which the question of the effect of maternal mood on infant outcomes was examined, specifically looking at stress, depression, and intimate partner violence, and not just the presence of these elements, but their duration and intensity both before and during the pregnancy (2015 Sep-Oct;64[5]:331-41).

To do this, researchers examined survey data from Utah’s Pregnancy Risk Assessment Monitoring System of 4,296 women who gave birth during 2009-2011. Stress, depression, and intimate partner violence, and the duration and severity of each, were determined by questionnaire. Those determinations were compared with the outcomes of gestational age, birth weight, neonatal ICU admission, and the symptoms and diagnosis of postpartum depression.

Results of the study included the following: Increased duration of depression was associated with a greater risk of neonatal ICU admission, particularly in women who were depressed both before and during their pregnancy (adjusted odds ratio, 2.48), compared with women who had no depression.

 

We’ve known for a long time that a history of depression predicts increased risk for postpartum depression. In this particular study, it was actually shown that not just a history of depression, but the duration of experienced depression influenced the risk for postpartum depression.

For example, compared with women with no depression, women who were depressed before but not during their pregnancy had an aOR of 7.67, women depressed during pregnancy but not before had an aOR of 17.65, and women depressed both before and during pregnancy had an aOR of 58.35 – an extraordinary stratification of risk, basically.

What these data begin to suggest is that there may be a continuum of risk when it comes to the effects of exposure to depression (factoring in now dose and duration of exposure) during pregnancy. If risk of adverse outcome increases with greater severity of perinatal psychiatric illness, then a mandate to treat depression during pregnancy, whether with pharmacologic or nonpharmacologic interventions (or, commonly, a combination of the two) becomes that much more imperative. Regardless of the treatment interventions that are used, the importance of treating depression during pregnancy and keeping women well before, during, and after pregnancy is so critical. Such a recommendation dovetails with the literature showing the intergenerational effects of untreated depression. Maternal depression is one of the strongest predictors of later childhood psychopathology. With current national trends moving toward mandating screening initiatives for postpartum depression, the appreciation of the extent to which depression before and during pregnancy drives risk for postpartum mood disorder broadens how we think about mitigating risk for puerperal mood disturbance. Specifically, mitigating the effects of postpartum depression on women, their children, and their families must include more effective management of depression both before and during pregnancy.

 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.