SSRIs increasingly prescribed during pregnancy, without much study on their effects

Lead researcher Claudia Lugo-Candelas

Researchers from Columbia University, the Keck School of Medicine, and the Institute for the Developing Mind in Los Angeles, have published a new study on how infants' brains are affected when their mothers take SSRIs for depression during pregnancy. SSRIs include Celexa, Lexapro, Prozac, Luvox, Paxil and Zoloft, and are used by 1 in 10 adults in the US.

Excerpts from the study:

Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood.

A cohort study conducted at Columbia University Medical Center and New York State Psychiatric Institute included 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated maternal depression exposure, and 61 healthy controls. Our findings suggest that prenatal SSRI exposure has an association with fetal brain development, particularly in brain regions critical to emotional processing....To our knowledge, this is the first study to report increased volumes of the amygdala and insular cortex, as well as increased WM connection strength between these 2 regions, in prenatally SSRI-exposed infants.

Lugo-Candelas C, Cha J, Hong S, et al. Associations Between
Brain Structure and Connectivity in Infants and Exposure to
Selective Serotonin Reuptake Inhibitors During Pregnancy. 
JAMA Pediatr. Published online April 09, 2018.
PMD = Prenatal Maternal Depression; HC = Healthy Control

The prescription of selective serotonin reuptake inhibitor (SSRI) medications for pregnant women has accelerated over the past 30 years. To some extent, this rise may be attributable to increased awareness of the detrimental effects of untreated prenatal maternal depression (PMD) on women and children, along with early studies failing to document immediate effects of SSRI exposure in offspring (although later rodent studies document postpubertal alterations). However, little is known about the association between prenatal SSRI exposure and human fetal neurodevelopment. Serotonin (5-hydroxytryptamine [5-HT]) plays a vital role in neurodevelopment.

In the fetal brain, 5-HT signaling affects cell proliferation, differentiation, neuronal migration, network formation, and synaptogenesis. Perinatal SSRI exposure in rodent studies is associated with delayed motor development, reduced pain sensitivity, disrupted thalamocortical organization, reduced dorsal raphe neuronal firing, reduced arborization of 5-HT neurons, and altered limbic and cortical circuit functioning.

Literature on prenatal SSRI exposure in humans is limited and mixed. Studies have most consistently reported that prenatal SSRI exposure is associated with a shorter gestational period, lower birth weight, lower Apgar scores, and neonatal abstinence syndrome....Consistent with animal studies, a recent national registry study (including 15 ,000 prenatally SSRI-exposed offspring) found increased rates of depression in early adolescence in youth with prenatal SSRI exposure.

Brain imaging provides a window into neurodevelopment, yet human infant and fetal imaging studies of prenatal SSRI exposure are scarce....The study highlights the need for further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.

One of the references the authors cite, a 2007 study titled, "Increasing use of antidepressants in pregnancy," says:

The proportion of pregnancies with antidepressant use increased from 5.7% of pregnancies in 1999 to 13.4% of pregnancies in 2003. The increase was mostly accounted for by increases in selective serotonin reuptake inhibitor exposures....There is an urgent need for further studies that better quantify the fetal consequences of exposure to antidepressants.