Antidepressants in Pregnancy Tied to Poorer Motor Function

Batya Swift Yasgur, MA, LSW

June 25, 2018

Children of women who take antidepressants during pregnancy may have a small increased risk for poorer motor development, new research suggests.

Investigators pooled results from 18 studies of children exposed to antidepressants during their mother's pregnancy and found a significant association between gestational exposure to antidepressants and overall occurrence of poorer motor outcomes.

However, methodologic variations among the studies and lack of control for possible confounders limit these findings.

"This review highlights the urgent need for investment in high-quality research to examine developmental outcomes for children where there is depression and antidepressant exposure in pregnancy," Megan Galbally, MBBS, MPM, FRANZCP, PhD, professor, Murdoch University of Notre Dame, Australia, told Medscape Medical News.

However, "there are no current take-home messages for clinicians or women, given the concerns raised in this review about study variations and quality of the identified studies included, so this remains an area for further investigation before making clinical recommendations," she said.

The study was published online June 21 in Pediatrics.

Biological Plausibility

"Rates of antidepressant prescribing during pregnancy have increased over the last 10 to 15 years, with estimates revealing an increase of between fourfold and 16-fold," the authors write.

Although most previous research has the examined short-term impact of these agents on neonates, some studies have examined longer-term effects on children during early childhood and through school years on cognitive, motor, neurobehavioral, and emotional development.

Early studies have suggested that fetal exposure to antidepressants may be associated with impairment in motor processes in infancy and early childhood, but results have been conflicting, the researchers add.

They note that there is "sufficient biological plausibility" of the potential impact of antidepressants on future motor development, since serotonin reuptake inhibitors readily cross the placenta and blood-brain barrier, potentially altering serotonin signaling and serotonin circuitry in a developing fetus.

Previous systematic literature reviews of the impact of prenatal antidepressant exposure and subsequent developmental outcomes did not focus exclusively on motor outcomes and the potential implications of motor deficiencies on a child's development.

"My clinical work is as a prenatal psychiatrist, where it is important to have information for women on the risks and benefits of treatments in pregnancy, since one of the main concerns raised by these women is whether there are longer-term risks for their unborn child if they take antidepressant medication in pregnancy," said Galbally.

The investigators examined developmental outcomes for children whose mothers had taken antidepressants during pregnancy and conducted a systematic review of the impact of antidepressant exposure on child development.

Those studies showed a "trend towards finding for motor outcomes but no other developmental domains," she said.

The researchers therefore wanted to "undertake a review and meta-analysis specifically on motor development to examine this finding across all current published studies," she said.

To investigate the question, the researchers conducted a search of the literature through July 24, 2017.

The 24 studies that met inclusion criteria for the systematic review reported primary data, were published in the English language, involved human beings, used an accepted measure of motor performance, and reported on infant or child motor development after antidepressant exposure in pregnancy.

For the meta-analysis, additional inclusion criteria were the inclusion of a control group of women who were not exposed to antidepressant medication during pregnancy and provision of sufficient raw data to perform effect size (ES) calculations. The researchers identified 18 studies that met these criteria.

Robust Research Needed

The ES for poorer motor outcomes after in utero antidepressant exposure in the pooled studies was 0.22 (95% confidence interval [CI], 0.07 - 0.37).

Seven studies reported outcomes of motor assessment with categorical data; for these studies, the pooled ES was significant (ES = 0.40; 95% CI, 0.18 - 0.62).

However, for the 11 studies that reported continuous data, the ES was nonsignificant (ES = 0.40; 95% CI, -0.11 to 0.26).

For the total pooled analysis and the analysis of the categorically reported data of motor outcomes, the researchers found significant heterogeneity measures (I2 = 56.6, P = .002; and I2 = 67.4, P = .005, respectively).

Significant heterogeneity was also found in the studies that reported motor assessment outcomes with continuous rather than categorical data for motor development (P = .018). These continuous-outcome studies yielded an I2 value of 34.2 (P = .125).

Metaregression analyses of potential predictors of heterogeneity found that the type of data (ie, categorical vs continuous) was a significant predictor of heterogeneity (P = .033).

A funnel plot analysis found no indication of publication bias.

The researchers noted several limitations in their study, including the fact that 13 different methods were used to quantify motor performance; only one study used a standardized and specific neuropsychological measure of motor development (the Movement Assessment Battery for Children).

To assess motor development, some studies used screening measures with motor components but no specific subscales and did not include clinical assessment and/or maternal report, making comparisons of results among studies difficult, the authors comment.

In addition, self-report methods are susceptible to recall bias, they note.

Lack of confounding by indication was another limitation in the original studies; only five of the 24 studies included in the systematic review included a control group of women who had depression but did not take medication during pregnancy.

"Future research needs to robustly measure exposure to antidepressants in pregnancy so we can be sure there is indeed exposure, include mental health confounding variables [in the research], and prospectively assess children using gold-standard measures of development in adequate numbers of participants," Galbally commented.

"Until we have this quality of research, we will continue to be unclear on the risks and benefits of treatment options for women," she said.

"Crucial Comparison"

Commenting on the study for Medscape Medical News, Louise Howard, MPhil, PhD, National Institute for Health Research research professor in women's mental health, King's College London, United Kingdom, who was not involved with the study, said it "highlights the methodological limitation of most studies carried out to date, particularly the failure of researchers to compare outcomes in children exposed to antidepressants in pregnancy with children of women who were depressed in pregnancy and did not take antidepressants."

She called this a "crucial comparison" because, without it, "we are unable to establish whether associations are due to the antidepressant or the depressor or to factors associated with depressive symptoms."

She added that first-line treatment for mild to moderate depression in pregnancy is psychological therapy, and if a woman has severe symptoms, an antidepressant is "appropriate" because untreated severe depression can have serious adverse effects for the fetus.

Galbally agreed, also emphasizing "the importance of detection and treatment of depression across the perinatal period, given the potential implications for maternal and child well-being from untreated mental disorders." She encouraged beginning with evidence-based psychotherapy.

She added that her group is currently conducting a larger prospective pregnancy cohort study that includes early motor outcomes.

The study received no external funding. Dr Galbally has received honoraria for speaking from Lundbeck; the other authors have disclosed no relevant financial relationships. Dr Howard chaired the NICE guidance on antenatal and postnatal mental health.

Pediatrics. Published online June 21, 2018. Abstract

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