Comparing the Effects of Prenatal Depression and its Treatment on Developmental Outcomes of the Offspring

ABSTRACT
The risk associated with both untreated depression and selective serotonin reuptake inhibitors (SSRIs)
treatment has presented a significant dilemma to the 20% of pregnant women suffering from prenatal
depression and their clinicians. Both prenatal depression and SSRIs have been found to adversely impact fetal
brain development. However, the limited epidemiologic research on neurodevelopmental outcomes of the
offspring suffers severe methodological limitations and thus, the literature is inconclusive. The proposed study
addresses these methodological limitations and leverages Kaiser Permanente Northern California’s (KPNC’s)
unique universal perinatal depression screening program to assemble a longitudinal birth cohort of >320,000
children from 0 to 8 years of age born between 2013-2020. As part of standard prenatal care, women are
screened for depression twice during pregnancy (at the first prenatal visit and 26-28 weeks) providing a large
cohort of women with depression and its severity measures throughout pregnancy. In addition, KPNC’s
universal childhood developmental screening program provides systematic screening for neurodevelopmental
disorders. The primary outcomes will be six neurodevelopmental disorder diagnoses defined in the DSM 5:
intellectual disability, global developmental delay, motor disorders, communication disorder, autism spectrum
disorder, and attention-deficit/hyperactivity disorder (ADHD); corresponding diagnosis codes will be
ascertained from KPNC’s electronic health records (EHR) and supplemented through linkage to California’s
Department of Developmental Services. We will use KPNC EHRs to ascertain information on important
confounders and link to the father’s medical records to ascertain information on psychiatric history. We will test
the hypothesis that the underlying prenatal depression and SSRIs are independent risk factors for adverse
neurodevelopmental outcomes and may differ by infant sex. We will evaluate the effect of untreated prenatal
depression, compared to no prenatal depression on the six neurodevelopmental outcomes of the offspring,
after adjusting for confounders. We will also assess the effects of treatment with SSRIs during pregnancy on
neurodevelopmental outcomes of the offspring compared to both untreated prenatal depression and treatment
with psychotherapy only, while taking into account depression severity and other confounders. Finally, to
examine their impact on less severe neurodevelopmental outcomes we will recruit a subsample of 2,000 5-
year old children (500 randomly chosen from each of four exposure categories: no prenatal depression,
untreated prenatal depression, treatment with SSRIs, treatment with psychotherapy only) to ascertain
information through parent interview on neurodevelopmental outcomes that may not meet the criteria of a
clinical diagnosis, but may suggest a need to monitor and/or provide early interventions. Findings from this
study will have significant public health and clinical implications by providing information that can be
immediately used by pregnant women and clinicians making treatment decisions.

Grant Number: 5R01HD101483-05
NIH Institute/Center: NIH
Principal Investigator: Lyndsay Avalos