Research Review: Developmental origins of depression - a systematic review and meta-analysis

Many observational studies have found a direct association between adverse in utero, perinatal and postnatal exposures and offspring's depression. These findings are consistent with the 'developmental origins of disease hypothesis'. But no review has comprehensively summarized the roles of these exposures. This review aims to systematically scrutinize the strength of associations between individual prenatal, perinatal, and postnatal exposures and subsequent depression in offspring.

We conducted a systematic review and meta-analysis to synthesize the literature from the EMBASE, HealthStar, PsychoInfo, and Medline databases since their inception to September 1, 2019. English language articles on population-based prospective cohort studies examining the associations between in utero, perinatal, and postnatal exposures and offspring's depression were searched. Random-effects models were used to calculate pooled estimates, and heterogeneity and sensitivity tests were conducted to explore potential confounders in the relationships of depression and early-life factors. Qualitative analysis was also conducted.

Sixty-four prospective cohort studies with 28 exposures studied in the relationships to offspring's depression met inclusion criteria. The meta-analysis found 12 prenatal, perinatal, and postnatal characteristics were associated with an increased risk of depression in offspring: low birth weight, premature birth, small gestational age, maternal education, socioeconomic status, having younger parents (<20 years), having older parents (≥35 years), maternal smoking, paternal smoking, maternal stress, maternal anxiety, and prenatal depression. Heterogeneity and sensitivity tests supported the findings. By and large, study characteristics had no effects on conclusions. Qualitative analyses generally supported the findings of meta-analysis and reported on additional risk factors.

This review provides a robust and comprehensive overview of the lasting psychopathological effects of in utero, perinatal, and postnatal exposures. The findings highlight the need for clinical and public health interventions focusing on the identified risk factors. Large prospective cohort studies are warranted to investigate the combined effects of multiple co-existing early-life exposures.