Association of Parental Prenatal Mental Health on Offspring Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

Abstract

Objective: Parental prenatal mood and anxiety disorders (PMAD) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors.

Method: A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to January 2024. Of 2,170 articles screened, 64 met the inclusion criteria. Meta-analyses were conducted on 20 studies, and 44 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I²) and publication bias (Egger's test). The review followed PRISMA and MOOSE guidelines.

Results: Maternal PMADs were associated with a significantly increased risk of ADHD (OR 1.91, 95% CI 1.45-2.52) and ASD (OR 1.57, 95% CI 1.37-1.81) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR 1.24, 95% CI 1.15-1.34). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior.

Conclusions and relevance: Parental PMADs are significantly associated with an increased risk of NDDs in children. These associations may be influenced by both genetic predispositions and environmental factors. Understanding these pathways is important for informing interventions aimed at mitigating mental health risks in families and supporting child development.

Keywords: anxiety disorders; attention-deficit/hyperactivity disorder; autism; intellectual disability; maternal; mood disorder; neurodevelopmental disorders; obsessive-compulsive disorder; paternal; prenatal.

Figure 1.

PRISMA flow diagram.

Figure 2.

Forest plot of associations between maternal prenatal mood and anxiety disorders and offspring neurodevelopmental disorders. Square sizes reflect the weights attributed to each study. Diamonds denote the summary effect sizes for the random-effect models. OR=odds ratio. CI=confidence intervals NDD=neurodevelopmental disorders. ADHD=attention-deficit/hyperactivity disorder. ASD=autism spectrum disorder. ^aClements et al (2015) analyzed separate samples of individuals with diagnoses of autism spectrum disorder and attention-deficit/hyperactivity disorder. The authors provided results for three trimesters. The third trimester has been selected for this meta-analysis because it is the most conservative estimate reported by Clements et al (2015). ^bChien et al (2022) included the following disorders: major depressive disorder, persistent depressive disorder, and depressive disorder, unspecified. ^cHope et al (2024) analyzed a combined sample of individuals with any of the following disorders: autism/autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy.

Figure 3.

Forest plot for the association between paternal prenatal mood and anxiety disorders and the risk of neurodevelopmental disorders (NDDs) in offspring. Square sizes reflect the weights attributed to each study. The diamond denotes the summary effect size for the random-effect models. CI=confidence intervals. ASD=autism spectrum disorder. ADHD=attention-deficit/hyperactivity disorder. ^aChien et al (2022) included the following disorders: major depressive disorder, persistent depressive disorder, depressive disorder, unspecified, generalized anxiety disorder, panic disorder, agoraphobia, social anxiety disorder, and specific phobia disorder.

Figure 4.

Maternal and paternal effect on offspring phenotype (a neurodevelopmental disorder). It includes three main pathways: the maternal/paternal genetic nurture effect, showing transmission from maternal/paternal genotype to their respective phenotypes and then to the offspring’s phenotype (dashed arrows 3 & 5); the environmental maternal/paternal effect, indicating the influence of the maternal or paternal environment on their phenotype and consequently on the offspring’s phenotype (dashed arrows 4 & 6); and the direct maternal/paternal genetic effect, which traces direct transmission from maternal/paternal genotype to the offspring’s genotype and then to their phenotype (dashed arrows 1 & 2). This figure omits child environment effects or gene-environment interactions.