Maternal Hypertensive Pregnancy Disorders and Mental Disorders in Children

Abstract

The associations of maternal hypertensive pregnancy disorders with offspring mental disorders remain unclear. We examined whether maternal hypertensive disorders and maximum blood pressure during pregnancy predict offspring childhood mental disorders, whether the associations are independent of maternal and paternal mental disorders and paternal hypertensive disorders, independent of or additive with maternal early pregnancy overweight/obesity and diabetes mellitus disorders, and mediated or moderated by preterm birth, small-for-gestational-age birth and neonatal intensive care unit admission. Our prospective study comprised 4743 mother-child dyads of Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. Women were recruited to the study in early pregnancy at Finnish maternity hospitals. Children were born 2006 to 2010 and followed-up until December 31, 2016, to ages 6.4 to 10.8 years. Hypertensive pregnancy disorders were identified from medical records, Medical Birth Register, and Care Register for Health Care. Systolic and diastolic blood pressure were measured at antenatal clinics and hospital visits. Mental disorder diagnoses were identified from Care Register for Health Care. Maternal gestational and chronic hypertension, preeclampsia and its severity increased offspring hazard of any childhood mental disorder. The associations of preeclampsia (hazard ratio=1.66 [95% CI, 1.14–2.42]) and severe preeclampsia (hazard ratio=2.01 [95% CI, 1.08–3.73]) were independent of all covariates. Maternal hypertensive and diabetes mellitus disorders and overweight/obesity also additively increased offspring hazard of mental disorders. Preterm and small-for-gestational-age births and neonatal intensive care unit admission partially mediated the effects of any and severe preeclampsia on offspring mental disorders. To conclude, maternal hypertensive pregnancy disorders carry adverse consequences for offspring mental health.

From Maternal Diet to Neurodevelopmental Disorders: A Story of Neuroinflammation

“…Growth alteration, altered behaviors (anxiety, ADHD, cognition, depression) Rizzo et al, 1991;Sussman et al, 2013Sussman et al, , 2015von Geijer and Ekelund, 2015 Kattah and Garovic, 2013;Kleinewietfeld et al, 2013;Mao et al, 2013;Ha, 2014;Choe et al, 2015;Seravalli et al, 2016;Stocher et al, 2018;Afroz and Alviña, 2019;Faraco et al, 2019;Riise et al, 2019;Lahti-Pulkkinen et al, 2020 O 'Connor et al, 1988;Huang et al, 2001;Gambling et al, 2002Gambling et al, , 2004Lozoff and Georgieff, 2006;Alwan and Hamamy, 2015;Means, 2020 Zinc ↓ Preterm delivery, prolonged labor, hypertension, increased risk of infection Death, fetal malformations, growth delay, seizure, altered behaviors (anxiety, hypotonia, ADHD, social deficits) Donangelo and King, 2012;Roohani et al, 2013;Grabrucker et al, 2014Grabrucker et al, , 2016Sauer and Grabrucker, 2019 ↓, reduced; ↑, increased; ↑↓, imbalance; ↑↑↑, excessive; ASD, autism spectrum disorders; ADHD, attention-deficit-hyperactivity disorders; C-section, cesarean section; CNS, central nervous system; N/A, not available. Buyken et al, 2014;Castanon et al, 2015;Ludwig et al, 2018;Montalvo-Martínez et al, 2018).…”

Maternal Hypertensive Pregnancy Disorders and Mental and Behavioral Disorders in the Offspring: a Review

“…Possible key confounding factors or moderators include familial confounding by maternal/parental mental health, other genetic or shared familial environmental influences, and maternal metabolic disorders during pregnancy (diabetes disorders and early pregnancy overweight/obesity). All these factors are highly comorbid with hypertensive pregnancy disorders [1,11,[27][28][29] and predict increased offspring risk of mental and behavioral disorders [30][31][32][33][34]. Furthermore, hypertensive pregnancy disorders increase the risk of preterm and SGA birth [5].…”

“…Of the ten cohort studies [8][9][10][11][12][13][14][37][38][39], eight reported significant associations between maternal hypertensive pregnancy disorders and increased offspring risk of mental and behavioral disorders and two reported null findings. All cohort studies had many methodological strengths and received 5-9 stars in the NOS assessment (Table 2 and Supplementary Table 1 in the Online Data Supplement).…”

“…Three representative prospective cohort studies from Norway [12], Canada [37], and Finland [11] each rated as having good methodological quality received seven stars in the NOS assessment. The Norwegian study among over one million mother-child dyads showed 1.3-1.4-fold (95% CIs=1.1-1.6) increased risk of ASD and 1.2-1.3-fold (95% CIs=1.1-1.4) increased risk of ADHD in offspring exposed to maternal preeclampsia [12].…”

“…Especially in recent years, an increasing amount of studies have also assessed the effects of maternal hypertensive pregnancy disorders on offspring mental and behavioral disorders [8][9][10][11][12][13][14]. In light of this and since earlier original research studies have been reviewed thoroughly in previous meta-analyses [15•, 16, 17-22], we reviewed the recent evidence from metaanalytic and new original research studies on maternal hypertensive pregnancy disorders and offspring mental and behavioral disorders published since 2015.…”