The Effect of Maternal Hypertension and Maternal Mental Illness on Adverse Neonatal Outcomes: A Mediation and Moderation Analysis in a U.S. Cohort of 9 Million Pregnancies.

Background: While hypertensive disorders of pregnancy (HDP) coexist with maternal anxiety and depression, it is unclear how these conditions affect neonatal outcomes. We evaluated the prevalence as well as associations and potential mechanisms between HDP, maternal anxiety and depression, preterm birth (PTB), and small for gestational age (SGA). Methods: We conducted a retrospective population-based study using the Healthcare Cost and Utilization Project (HCUP) database from 2004 to 2014. Preterm birth (<37 weeks), SGA (<10th percentile for gestational age and sex), HDP, and mental disorders (anxiety and depression) were extracted using the International Classification of Diseases, Ninth Revision (ICD-9). Mediation and moderation models were constructed separately to evaluate potential mechanisms between maternal anxiety and depression, HDP, and adverse neonatal outcomes. Multivariate logistic regressions were used to determine their associations. Results: Of 9,097,355 pregnant women, the prevalence of HDP was 6.9 %, anxiety 0.91 %, depression 0.36 %, preterm birth 7.2 %, and SGA 2.1 %. Anxiety increased the probability of having HDP (OR = 1.242, 95 % CI 1.235-1.250), and HDP mediated the association between anxiety and preterm birth (mediation effect = 0.048, p-value<0.001). Depression significantly moderated the effect of HDP on preterm birth (moderation effect = -0.126, p-value = 0.027). HDP also mediated the association between anxiety and SGA (mediation effect = 0.042, p-value<0.001), but depression did not moderate the association between HDP and SGA (p-value = 0.29). Conclusion: Our study suggests that women with anxiety are more likely to have HDP, and HDP mediates the associations between anxiety and adverse neonatal outcomes. Depression moderates associations between HDP and preterm birth but not between HDP and SGA.