Abstract
Maternal preeclampsia has been reported to increase the risk of autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability in offspring. However, the association between maternal preeclampsia combined with perinatal complications and neurodevelopmental and psychiatric disorders in offspring is less well documented. To examine the association of maternal preeclampsia, separately and together with perinatal complications, with neurodevelopmental and psychiatric disorders in offspring. This population-based cohort study used data from nationwide registries in Finland to assess all singleton live births (N = 1 012 723) between January 1, 1996, and December 31, 2014. Offspring were followed up until December 31, 2018 (when the oldest reached age 22 years). Exclusion criteria were maternal inpatient psychiatric diagnoses and pregestational diabetes. The study and data analysis were conducted from May 1, 2020, to June 1, 2021. Preeclampsia and perinatal complications (delivery earlier than 34 weeks' gestation and/or small for gestational age). The primary outcomes were neurodevelopmental and psychiatric diagnoses and dispensation of psychotropic drugs among offspring until December 31, 2018. Cox proportional hazards regression analyses were performed to assess the associations. Of 1 012 723 singleton live births (51.1% boys; mean [SD] maternal age at birth, 30.0 [5.4] years; specific data on race and ethnicity were not available in the data set), 21 010 children (2.1%) were exposed to preeclampsia alone, 33 625 children (3.3%) were exposed to perinatal complications alone, and 4891 children (0.5%) were exposed to both preeclampsia and perinatal complications. A total of 93 281 children (9.2%) were diagnosed with a neurodevelopmental or psychiatric disorder. Offspring exposed to both preeclampsia and perinatal complications had an increased risk of any neurodevelopmental or psychiatric disorder after adjusting for potential confounding (adjusted hazard ratio [aHR], 2.11; 95% CI, 1.96-2.26) compared with those not exposed to either preeclampsia or perinatal complications; this risk was higher than exposure to either preeclampsia alone (aHR, 1.18; 95% CI, 1.12-1.23) or perinatal complications alone (aHR, 1.77; 95% CI, 1.72-1.82). Sibling pair analyses did not detect any increase in the risk of neurodevelopmental or psychiatric disorders after exposure to preeclampsia alone, but offspring exposed to both preeclampsia and perinatal complications had increased risks of intellectual disabilities (aHR, 3.24; 95% CI, 1.05-10.06), specific developmental disorders (aHR, 3.56; 95% CI, 2.35-5.41), ADHD and conduct disorders (aHR, 2.42; 95% CI, 1.09-5.39), and other behavioral and emotional disorders (aHR, 2.45; 95% CI, 1.17-5.13). The risk estimates for specific developmental disorders (aHR, 2.82; 95% CI, 2.60-3.05) and ADHD and conduct disorders (aHR, 1.88; 95% CI, 1.65-2.14) were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications alone (aHR, 2.26 [95% CI, 2.18-2.33] and 1.60 [95% CI, 1.52-1.68], respectively). In this study, exposure to both maternal preeclampsia and perinatal complications was associated with intellectual disabilities, specific developmental disorders, ADHD and conduct disorders, and other behavioral and emotional disorders in offspring. For specific developmental disorders and ADHD and conduct disorders, the risk estimates were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications only.
Highlights
Preeclampsia, occurring in 3% to 5% of pregnancies worldwide, is characterized by new-onset hypertension along with proteinuria after 20 weeks’ gestation and is often accompanied by uteroplacental dysfunction with abnormal blood vessel development and other maternal organ dysfunction.[1-3]
Sibling pair analyses did not detect any increase in the risk of neurodevelopmental or psychiatric disorders after exposure to preeclampsia alone, but offspring exposed to both preeclampsia and perinatal complications had increased risks of intellectual disabilities, specific developmental disorders, attention-deficit/hyperactivity disorder (ADHD) and conduct disorders, and other behavioral and emotional disorders
For specific developmental disorders and ADHD and conduct disorders, the risk estimates were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications only
Summary
Preeclampsia, occurring in 3% to 5% of pregnancies worldwide, is characterized by new-onset hypertension along with proteinuria after 20 weeks’ gestation and is often accompanied by uteroplacental dysfunction with abnormal blood vessel development and other maternal organ dysfunction.[1-3]. Preeclampsia is a major factor associated with maternal and perinatal morbidity and mortality associated with eclampsia, stroke, and kidney failure as well as hemolysis, elevated liver enzymes, and low platelet syndrome.[4]. Preeclampsia has been associated with long-term endocrine and cardiovascular morbidity in offspring.[5-7]. Given that delivery is the only effective treatment for preeclampsia, delivery before 34 weeks’ gestation is often used as a retrospective proxy for severe preeclampsia.[8]. Because small for gestational age (SGA) status at birth is associated with uteroplacental dysfunction, preeclampsia combined with SGA status is considered a severe condition.[9,10]
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