Depression during pregnancy posed problems for the developing fetus and newborns, regardless of whether the mother received treatment, investigators reported.
Women who took the selective serotonin reuptake inhibitor (SSRI) class of antidepressants during pregnancy had fewer depressive symptoms, but babies had delayed fetal head growth and an increased risk of preterm birth.
Untreated maternal depression was associated with delayed fetal head growth -- though not as much as for mothers taking SSRIs -- and delayed fetal body growth, according to an article published online in Archives of General Psychiatry.
The dilemma arising from the retrospective cohort study left the authors with no simple answers.
"Although our findings add to current knowledge about the consequences of SSRI use (or nonuse) in women with depressive symptoms during pregnancy, they are not conclusive," Henning Tiemeier, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors wrote in the discussion.
"Most importantly, untreated women with depressive symptoms also have children with reduced growth of the fetal head, albeit less prominently. Nevertheless, our findings are of important value because there is a paucity of data regarding safety of SSRI use during pregnancy and possible consequences on fetal health."
Despite widespread use during pregnancy, SSRI antidepressants have not been studied extensively with respect to their effects on fetal development.
Animal studies have shown that serotonin has a key role in prenatal brain development. Studies in mice showed that prenatal exposure to SSRIs was associated with smaller head size.
Additionally, mice deficient in serotonin transporter had high levels of serotonin, which was associated with neuroanatomical deficits, which, in turn, were associated with disturbed behavior later in life, the authors wrote in their introduction.
The scant clinical data on prenatal effects of SSRIs include evidence of nonsignificant delays in motor milestone development. Untreated depression during pregnancy also has been linked to adverse pregnancy outcomes and neonatal complications, the authors continued.
Given the modest knowledge base, Tiemeier and colleagues retrospectively analyzed data from an ongoing prospective cohort study. Investigators examined associations among depressive symptoms during pregnancy, maternal use of SSRIs, fetal head and body growth, and birth outcomes.
To assess maternal SSRI use, the authors evaluated patients' self-reported use and prescription records. Depression was assessed by means of the Brief Symptom Inventory at an average of 20.6 weeks' gestation.
The final analysis comprised 7,696 women: 7,027 who did not use SSRIs and had low depressive symptom scores (control group); 570 women with clinically relevant but untreated depressive symptoms; and 99 women who used SSRIs during pregnancy.
Fetal ultrasonography was performed at a median gestation of 12.8 weeks, 20.3 weeks, and 30.1 weeks.
The primary outcomes were fetal body and head growth, preterm birth, small for gestational age, and low birth weight.
Fetuses of mothers with untreated depression had significantly lower body growth (-4.4 g/week, P<0.001) and head growth (-0.08 mm/week, P=0.003) compared with fetuses of mothers in the control group.
Women with untreated depression had significantly more depressive symptoms compared with the control group (P<0.001) and with the women who took SSRIs during pregnancy (P<0.001).
Among women who took SSRIs during pregnancy, fetal body growth did not differ significantly from that of the control group. However, fetal head growth was significantly reduced (-0.18 mm/week, P=0.003).
With respect to birth outcomes, women who used SSRIs during pregnancy had a twofold increase in the odds of preterm birth compared with the control group (OR 2.14, P=0.03). The women with untreated depression did not differ significantly from the control group.
"Our study shows a rather specific effect of maternal SSRI use on fetal head growth, one of the best prenatal markers of brain volume," the authors wrote of their findings.
"Fetal head circumference in early life has been shown to be an accurate indicator of brain weight. Small head size in neonates predicts behavioral problems and psychiatric disorders ... Nonetheless, we must be careful not to infer an association of SSRI use in pregnancy with future developmental problems."
The study added little in the way of new information about SSRI use during pregnancy, said Lucy Puryear, MD, who has appointments in ob/gyn and psychiatry at Baylor College of Medicine in Houston.
Like studies that preceded it, the investigation did not address a key aspect of depression during pregnancy.
"There is a lot of focus on the effects of the depression on the baby or the effects of the medication on the baby, but it's almost as if the mother's health isn't considered," Puryear told MedPage Today.
"For the mother who has depression, it's a medical illness that she is suffering from, and it can cause her lots of problems in other relationships -- marriage, relationships with other children, problems at work. This is an interesting field, because you can't just focus on the fetus, you also have to focus on the mother."
Puryear also noted that a substantial proportion of the women treated with SSRIs still had significant depression, meaning the fetus was exposed to the effects of the medication and the depression.
Nonpharmacologic alternatives have demonstrated efficacy in depression and avoid potential adverse effects of drug treatment, she added. Behavioral therapy is one option, and transcranial magnetic brain stimulation is an emerging therapy that has shown considerable promise in studies to date.
The study was supported by the Netherlands Organization for Health Research and Development and by Sophia Children's Hospital in Rotterdam. The authors had no dislosures
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner