Several recent articles provide additional information about the effects on the infant of exposure to SSRI antidepressants during pregnancy.
A large study published in Pediatrics adds to information that suggests that exposure to SSRI antidepressants, particularly late in pregnancy, may be associated with birth complications.
As with other studies, one major limitation in the design of the study is that it looked at data from a large registry, and so could not distinguish between risks of birth complications due to depression in the mother (which then may have led to taking the SSRI) and birth complications due to the SSRI itself. From other studies we do know that untreated depression is also associated with birth complications.
In an attempt to address this limitation the study looked at exposure to SSRI’s early in pregnancy and compared results from that group to the results in women who received SSRI’s late in pregnancy.
The primary outcome was admission whether or not the infant was admitted to the neonatal ICU after birth. It’s worth noting that at least in this country pediatricians have a low threshold for admitting SSRI exposed infants to the NICU, so another limitation of the study is that we don’t know to what extent a higher rate of admissions reflected real complications or just increased caution.
|No SSRI||Early SSRI||Late SSRI|
|Percent admitted to NICU||8.2%||10.8%||16.5%|
The SSRI-exposed children were admitted to the NICU for a variety of reasons. The most common reasons for admission were for respiratory disorders (5.7%), most commonly transient tachypnea (4.6%). Other common reasons for admission included hyperbilirubinemia (5.2%), hypoglycemia (4.0%), and feeding difficulties (1.3%). These were also the most common reasons for admission in non-exposed infants; however, for some, but not all, causes, SSRI-exposed children were more likely than unexposed children to be admitted.
The authors also looked at risk for persistent pulmonary hypertension of the newborn (PPHN) in SSRI-exposed infants. PPHN was more common when comparing SSRI exposure versus nonexposure (OR: 1.3 [95% CI: 1.0–1.6]; P = .03) and when comparing treatment during late versus early in pregnancy (OR: 2.1 [95% CI: 1.3–3.2]).
Ruta Nonacs from the Massachusetts General Hospital Center for Women’s Mental Health, one of the premiere research settings for the study of perinatal outcomes, summarized the study this way…
Putting aside those limitations, it does appear that this study is consistent with previous studies. Exposure to antidepressants, including SSRIs, have been associated with an increased risk of adverse outcomes, including poor neonatal adaptation. In the current study, the risk of PPHN is also elevated in SSRI-exposed infants, but not to the extent observed in the earliest studies from Chambers and colleagues (2005). It is important to emphasize that even if we assume a modest increase in the risk of neonatal morbidity in infants exposed to SSRIs, the absolute risk is small and it may not justify avoiding or discontinuing antidepressants during pregnancy.
Another recent study looks at longer term outcomes in those exposed to SSRI’s.
The second study was a prospective study using Finnish medical and prescription databases for 56,340 infants and their mothers between 1996 and 2010.
The three study groups were 15,596 children whose mothers filled at least one SSRI prescription for a psychiatric disorder at around the time of pregnancy (notice that this is more than a quarter of all mothers!), 9537 whose mothers had a psychiatric disorder associated with SSRI use but did not fill an SSRI prescription, and 31,207 children without a psychiatric disorder or an SSRI prescription.
The researchers then looked at assessments for neurodevelopment in the children. Mean ages for assessments were 4.4 years for speech/language, 3.6 years for scholastic skills, and 7.7 years for motor disorders.
Offspring of mothers who purchased SSRIs at least twice during pregnancy had a significant 37% increased risk of speech/language disorders compared with offspring in the unmedicated group. The cumulative hazard of speech/language disorders was 0.0087 in the SSRI-exposed group (0.87% risk) vs 0.0061 (0.61% risk) in the unmedicated group (hazard ratio, 1.37; 95% CI, 1.11-1.70; P = .004).
The study is useful in that it looked at longer term outcomes, however the results were perhaps less clear than news accounts may have suggested. Overall, there were no significant differences between outcomes for the children born to women with untreated depression and women with depression treated with SSRI’s. There was a suggestion that women exposed to SSRI’s may have had infants with more speech and language difficulties than women without psychiatric problems but the difference, while statistically significant, was not large. Assuming that all of the difference was due to SSRI effects on the infant, the risk of speech and language difficulties increased from 7 per thousand in the women with depression who did not get SSRI’s to 9 per thousand in those with two or more SSRI prescriptions.
There are several important limitations in this study. The most obvious is that it is likely that the women who had two or more SSRI prescriptions included the group of women with more severe depression ( as compared with those women who had a diagnosis of depression but did not get SSRI prescriptions). Since this study also found that women with depression who did not get SSRI’s had children with similar (but less severe) difficulties to the women with depression who did get SSRI’s the results could all just reflect the impact of depression on speech and language acquisition, which we know is significant.
Another limitation in this study is that it did not control for alcohol use, which is higher in women with depression, and higher the more severe the depression, and which we know has profound impact on neurodevelopmental outcomes.
My takeaway from these two studies is that maternal depression clearly has a profound impact on outcomes and that the specific effects of SSRI’s on outcome are probably not as large as the effects of maternal depression.
It is worth noting, that TMS is a treatment for depression which has no effects on the fetus and is undoubtedly underutilized in this population.
Nörby U, Forsberg L, Wide K, Sjörs G, Winbladh B, Källén K. Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy. Pediatrics October 2016.
Brown AS, Gyllenberg D, Malm H, McKeague IW, Hinkka-Yli-Salomäki S, Artama M, Gissler M, Cheslack-Postava K, Weissman MM, Gingrich JA, Sourander A. Association of Selective Serotonin Reuptake Inhibitor Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring. JAMA Psychiatry. 2016 Nov 1;73(11):1163-1170. doi: 10.1001/jamapsychiatry.2016.2594. PubMed PMID: 27732704.