Preeclampsia and perinatal complications associated with increased risk neurodevelopmental and psychiatric diagnoses

1. A population-based retrospective cohort study found that the risk of certain psychiatric and neurodevelopmental diagnoses was higher in births exposed to maternal preeclampsia and perinatal complications compared to preeclampsia alone.

2. Increased risk for the following were identified: certain developmental disorders, attention deficit hyperactivity disorder (ADHD) and conduct disorder.

Evidence Rating Level: 2 (Good)

Study Rundown: Preeclampsia is a hypertensive disorder of pregnancy that can pose risk to the long term well-being of both mother and infant, and often necessitates delivery prior to term to optimize outcomes. Preeclampsia in combination with other perinatal complications, particularly fetal growth abnormalities (e.g., small for gestational age [SGA] babies) is considered a risk factor for a number of adverse mental health and neurodevelopmental outcomes. This large, population-based retrospective cohort study sought to describe the association between neurodevelopmental and psychiatric disorders and exposure to maternal preeclampsia alone versus in combination with perinatal complications. Amongst 1,012,723 live births occurring in Finland between 1996-2014, 2.1% (21,010) were exposed to maternal preeclampsia alone, 3.3% (33,625) to perinatal complications alone, and 0.5% (4891) to both. Mean follow-up time was 12.4 years, during which 9.2% (93,281) of children were diagnosed with neurodevelopmental or psychiatric disorders. The cumulative incidence of neurodevelopmental or psychiatric diagnoses was higher in children exposed to both maternal preeclampsia and perinatal complications compared to the preeclampsia group alone. In particular, elevated risk for specific neurodevelopmental disorders, ADHD and conduct disorder, was identified, as well as for dispensing of psychotropic medications. Kong et al concluded that preeclampsia in combination with perinatal complications of SGA or preterm delivery (<34 weeks) is associated with a higher risk of neuropsychiatric diagnoses in childhood compared to either risk factor alone. This study demonstrates the importance of population-wide prenatal care in anticipation of, and for the prevention of, such complications later in life. Strengths of this study include the large sample size and longitudinal follow up period. Additionally, the finding were robust to a number of sensitivity analyses which further strengthens their validity. Drawbacks of the study include the retrospective nature which makes it impossible to completely control for confounding, as well as the lack of information about the multitude of other factors in childhood which may contribute to a neuropsychiatric diagnosis.

Click here to read this study in JAMA Network Open

Relevant reading: Association between preeclampsia and autism spectrum disorder: a population based study

In Depth [cohort study]: Data from over 1,000,000 singleton live-births occurring in Finland between January 1, 1996 and December 31, 2014 were considered. Data were obtained from the Finnish national Drugs and Pregnancy Database. Patients with a history of maternal preeclampsia and/or perinatal complications (SGA and/or delivery prior to 34 weeks gestational age) were included. Exclusion criteria included: maternal gestational diabetes, maternal history of inpatient psychiatric admission and maternal hypertension (chronic or gestational).  International classification of diseases codes were used to identify diagnostic codes corresponding to relevant exposure and outcome data. Covariate demographic information was also collected. The most commonly diagnosed disorders amongst the 93,281 children experiencing the primary outcome in this study were as follows: specific neurodevelopmental disorders (5.5%), anxiety disorders (5.0%), mood disorders (3.8%) and ADHD/conduct disorder (3.0%). The adjusted hazard ratio (HR) for any neuropsychiatric disorder in patients with exposure to both preeclampsia and complications compared to preeclampsia alone was 1.18 (95% confidence interval 1.12-1.23). The HR for combination exposure compared to perinatal complications alone was 1.77 (1.72-1.82). The HR for neuropsychiatric disorder with both complications and preeclampsia was 2.11 (1.96-2.26) compared to the control group. The adjusted HR for diagnosis of the following were increased in the combined group compared to preeclampsia alone: specific developmental disorders (1.24, 1.18-1.31) and conduct disorder (1.22, 1.13-1.31). Children with combined risk were also more likely to be prescribed & dispensed psychotropic medications (HR 1.52, 1.35-1.71). Sibling pair analysis was conducted to assess for potential familial confounding factors and suggested that no confounding was present in the associations described.

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