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.
Despite the high prevalence of women with prenatal depression, increasing treatment with SSRIs in conjunction with increasing prevalence of neurodevelopmental disorders, and evidence from animal models suggesting both prenatal depression and SSRIs may alter the normal processes of fetal brain development, our understanding of the long-term effects in humans remains poor. This longitudinal birth cohort study will evaluate the impact of prenatal depression and its treatment on 1) important clinical neurodevelopmental disorders in over 320,000 children up to eight years of age all born at Kaiser Permanente Northern California (KPNC) hospitals between 2013-2020 to women universally screened for prenatal depression and 2) less severe neurodevelopmental outcomes that do not meet the criteria for a clinical diagnoses in a subsample of 2,000 five-year-old children ascertained through parent interviews using standard and well-established instruments. Findings from this study will have significant public health and clinical implications by providing information that can be used immediately by pregnant women and clinicians making treatment decisions for prenatal depression.
