Hypertensive Diseases of Pregnancy and the Development of Behavioral Problems in Childhood and Adolescence: The Western Australian Pregnancy Cohort Study

doi:10.1016/j.jpeds.2008.07.061

The Journal of Pediatrics

Volume 154, Issue 2, February 2009, Pages 218-224.e2

https://doi.org/10.1016/j.jpeds.2008.07.061 Get rights and content

Objective

To examine whether maternal gestational hypertension and preeclampsia are associated with behavioral problems in offspring throughout childhood and early adolescence.

Study design

We conducted a prospective cohort study of 2804 women in the Western Australian Pregnancy Cohort Study and their children observed at age 2, 5, 8, 10, and 14 years. The Child Behavior Checklist (CBCL) was used to measure problem child behavior with continuous z-scores and clinical cutoff points. Control variables included known biomedical, sociodemographic, and psychological factors.

Results

After adjustment, with general linear model analyses children of women with gestational hypertension were shown to be more likely to have higher CBCL z-scores, indicative of poorer behavior, from 8 years on, with the largest difference seen at 14 years. Children of mothers with preeclampsia were more likely to have lower CBCL z-scores, indicative of pro-social behaviors. The multivariable logistic regression analysis showed that gestational hypertension was predictive of clinically significant CBCL T-scores from age 8 to 14 years. This association was significant for externalizing behavior, such as delinquent and aggressive behavior, and for internalizing behavior at age 14 years. Unexpectedly, preeclampsia reduced internalizing morbidity at ages 5 and 8 years.

Conclusions

The opposing effect on child and adolescent behavior of gestational hypertension and preeclampsia warrants further attention.

Section snippets

Methods

The Western Australian Pregnancy Cohort (Raine) Study is a prospective pregnancy cohort study following women who were recruited at or around 18 weeks gestation (n = 2979) through the public antenatal clinic at King Edward Memorial Hospital (KEMH) and nearby private clinics in Perth, Western Australia, from May 1989 through to November 1991. The enrollment methods are reported in full elsewhere.¹² In brief, to be eligible for enrollment, the women were required to have a pregnancy between 16

Results

The behavioral morbidity data (total, internalizing, and externalizing) at each follow-up is presented in Table II by gestational hypertension and preeclampsia status. The clinical and sociodemographic characteristics of the sample are listed in Table III. During pregnancy, 22% of the total sample had a diagnosis of gestational hypertension and 3% of the total sample had a diagnosis of preeclampsia.

Discussion

A significant relationship between gestational hypertension and behavior is not observed until age 8 years. This latency effect may reflect a developmental proximity to the age when most children have more firmly established behavioral control.²⁰ At ages 2 and 5 years, there are lower demands on the child to self-regulate behavior, and possibly mothers of these pre-school children were less likely to view and rate their child's behavior as unusual or problematic.²⁰ The results for externalizing

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Placental dysfunction: The core mechanism for poor neurodevelopmental outcomes in the offspring of preeclampsia pregnancies
2022, Placenta
Preeclampsia (PE) is a leading condition threatening pregnant women and their offspring. The offspring of PE pregnancies have a high risk of poor neurodevelopmental outcomes and neuropsychological diseases later in life. However, the pathophysiology and pathogenesis of poor neurodevelopment remain undetermined. Abnormal placental functions are at the core of most PE cases, and recent research evidence supports that the placenta plays an important role in fetal brain development. Here, we summarize the relationship between abnormal fetal brain development and placental dysfunction in PE conditions, which include the dysfunction of nutrient and gas-waste exchange, impaired angiogenesis stimulation, abnormal neurotransmitter regulation, disrupted special protectors, and immune disorders. All these factors could lead to poor neurodevelopmental outcomes.
Hypertensive Disorders of Pregnancy and Behavioural Outcomes in the Offspring: Findings from the Millennium Cohort Study
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Citation Excerpt :
Some of the potential aetiological pathways linking HDP and neurodevelopment include alterations in neuroanatomical and functional connectivity in the brain of exposed offspring leading to behavioural issues (Figueiró-Filho et al., 2017; Mak et al., 2018; Ratsep et al., 2016), while it also possible that the inflammatory response associated with HDP could play a role given that maternal inflammation is a recognised risk factor for adverse neurodevelopmental outcome (Jiang et al., 2018). Several studies to date have examined the association between HDP and behavioural outcomes in the offspring (Bohm et al., 2019; Dachew et al., 2019; Glasson et al., 2004; Maher et al., 2020; Polo-Kantola et al., 2014; Robinson et al., 2009a; Wu et al., 2009). However, results have largely been conflicting, potentially due to use of different measures of HDP (for example, medical records vs. self-report), different measures of behavioural outcomes, and varying degrees of adjustment for confounding and ranges in follow-up (Bohm et al., 2019; Glasson et al., 2004; Robinson et al., 2009a).
The aim of this study was to examine the association between hypertensive disorders of pregnancy (HDP) and behavioural outcomes in offspring at five time-points.
We used maternal-reported data from the Millennium Cohort Study. Data on HDP were collected when children were 9-months. Data on behavioural outcomes were collected at age 3, 5, 7, 11 and 14years using the Strengths and Difficulties Questionnaire (SDQ). Multivariate logistic regression analysis examined a HDP-behavioural difficulties relationship, using validated SDQ cut-off points. Multilevel models with linear splines examined the association between HDP and repeated measures of SDQ.
18,274 singleton children were included in the study at baseline, Multivariate logistic regression suggested HDP was not significantly associated with SDQ domain cut-off points at ages 3, 7 and 11years. At age 5years, HDP was associated with a 40% increased odds of behavioural difficulties based on total SDQ(≥17) (OR:1.40, 95% CI:1.03,1.91). HDP was associated with a 43% increased odds of Peer Problem difficulties at age 5 (OR:1.43, 95% CI:1.10,1.86), and a 28% increased odds of Peer Problem difficulties(≥4) at age 14 (OR:1.28, 95% CI:1.02,1.61). In the linear spline model, mean SDQ score was higher at each time-point in those exposed to HDP, although did not always reach statistical significance.
Data on different classifications of HDP were unavailable; therefore, we could not examine the effect of gestational hypertension and preeclampsia separately.
While we did not find strong evidence of associations between HDP and behavioural outcomes overall, some associations between HDP and behavioural difficulties did persist at age 5 and 14years.
Disadvantaged neighborhoods, birth weight, and problem behavior in five- and six-year-old pre-school children: Evidence from a cohort born in Amsterdam
2020, Social Science and Medicine
Low birth weight has been found to increase the problem behavior of children. Yet, little attention has been given to adequately account for the impact of the child's neighborhood on this relation. The residential neighborhood is a choice, based on factors that are usually not observed that may also influence birth weight and problem behavior.
Using a model that accounts for such endogeneity of both neighborhood choice and birth weight, we have analyzed behavioral problems in 4210 pre-school children between the ages of 5 and 6, birth weight, and neighborhood status, simultaneously.
The data used are from the Amsterdam Born Children and their Development (ABCD) cohort for whom a complete prospective record of birth outcomes, pregnancy, socio-demographic characteristics, and indicators of problem behavior are available. Neighborhood data obtained from Statistics Netherlands are merged with the ABCD data file.
Our results suggest that ignoring endogeneity attenuates the effect of disadvantaged neighborhoods on both birth weight and problem behavior in pre-school children. Living in a disadvantaged neighborhood decreases the birth weight and increases the probability of problem behavior. Accounting for the endogeneity of neighborhood choice increases the estimated impacts (marginal effects: from −10% to −44% for birth weight and from 3% to 11% for problem behavior). Lower birth weight increases the probability of problem behavior, but it is only significant after adjusting for endogeneity. The coefficients of other factors have the expected associations with problem behavior.
These significant effects of disadvantaged neighborhood on birth weight and problem behavior could inform policies and practices that improve neighborhood development for children born in Amsterdam.
Neurodevelopmental Outcomes of Prenatal Preeclampsia Exposure
2020, Trends in Neurosciences
Preeclampsia is a dangerous hypertensive disorder of pregnancy with known links to negative child health outcomes. Here, we review epidemiological and basic neuroscience work from the past several decades linking prenatal preeclampsia to altered neurodevelopment. This work demonstrates increased rates of neuropsychiatric disorders [e.g., increased autism spectrum disorder, attention deficit hyperactivity disorder (ADHD)] in children of preeclamptic pregnancies, as well as increased rates of cognitive impairments [e.g., decreased intelligence quotient (IQ), academic performance] and neurological disease (e.g., stroke and epilepsy). We also review findings from multiple animal models of preeclampsia. Manipulation of key clinical preeclampsia processes in these models (e.g., placental hypoxia, immune dysfunction, angiogenesis, oxidative stress) causes various disruptions in offspring, including ones in white matter/glia, glucocorticoid receptors, neuroimmune outcomes, cerebrovascular structure, and cognition/behavior. This animal work implicates potentially high-yield targets that may be leveraged in the future for clinical application.
Hypertensive disorders of pregnancy and the risk of anxiety disorders in adolescence: Findings from the Avon Longitudinal Study of Parents and Children
2019, Journal of Psychiatric Research
The effect of hypertensive disorders of pregnancy (HDP) on offspring anxiety disorders in adolescence is not yet known. This study aims to examine the association between HDP and offspring anxiety disorders at age 15 years.
We used data from 5231 mother–offspring pairs from the United Kingdom based Avon Longitudinal Study of Parents and Children (ALSPAC). Anxiety disorder was diagnosed in the offspring at the age of 15 years using the Development and Well-Being Assessment (DAWBA).
Among those who had anxiety disorders, 16.4% were exposed to HDP. After adjusting for a wide range of known confounders, we found that adolescents of women with HDP had a 2.43 fold (95% CI: 1.41–4.19) increase risk of anxiety disorders compared with adolescents of women without HDP.
Our study showed that adolescents exposed to HDP had higher risk of anxiety disorders compared with unexposed adolescents and suggests that prevention and treatment of maternal HDP could possibly prevent offspring anxiety in adolescence. Early screening for anxiety disorders in offspring of women with HDP may also be warranted. Further research is needed to explain the pathways by which HDP may increase the risk of offspring psychopathology.
State-of-the-Art Diagnosis and Treatment of Hypertension in Pregnancy
2018, Mayo Clinic Proceedings
Hypertension complicates up to 10% of pregnancies worldwide. Pregnancy hypertension is defined as systolic blood pressure (BP) equal to or greater than 140 mm Hg or diastolic BP equal to or greater than 90 mm Hg, usually on the basis of measurements in office/clinic settings and using various BP devices. Hypertensive disorders of pregnancy are classified into (1) chronic hypertension diagnosed before pregnancy or before 20 weeks' gestation, (2) gestational hypertension diagnosed at equal to or greater than 20 weeks, or (3) preeclampsia, defined restrictively as gestational hypertension with proteinuria or broadly as gestational hypertension with proteinuria or an end-organ manifestation consistent with preeclampsia. Absolute BP values equal to or greater than 140/90 mm Hg are associated with increased maternal and perinatal risks, particularly with preeclampsia. This review focuses on antihypertensive therapy of hypertensive disorders of pregnancy as a specific management strategy. Underpinning this therapy is the need for accurate measurement of BP, agreed-upon classification of pregnancy hypertension, agreed-upon BP thresholds for enhanced surveillance and antihypertensive treatment, and collaborative teamwork in management. Challenges relate to the methodology of studies on which care is based, as well as aspects of the care itself, particularly the unregulated use of home BP monitoring. Pitfalls include the unsubstantiated belief that nifedipine and magnesium sulfate cannot be used together and the perception that severe hypertension and nonsevere hypertension are separate entities rather than lying along a spectrum of BP values. The following must be addressed by future research: guidance for nuanced care as women transition between severe and nonsevere hypertension, personalized antihypertensive therapy, and incorporation of women's values into research priorities and clinical practice when antihypertensive care is chosen.

View all citing articles on Scopus

: The Western Australian Pregnancy Cohort Study is funded by the Raine Medical Research Foundation, the National Health and Medical Research Council (NHMRC) of Australia, the Telstra Foundation, and the Western Australian Health Promotion Foundation. The authors declare no conflicts of interest.

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Original articleHypertensive Diseases of Pregnancy and the Development of Behavioral Problems in Childhood and Adolescence: The Western Australian Pregnancy Cohort Study

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Obstet Gynecol

Semin Fetal Neonatal Med

Lancet

J Psychosom Res

Obstet Gynecol

Lancet

Lancet

Lancet

Lancet

Int J Gynaecol Obstet

Med Hypotheses

Lancet

Neurosci Biobehav Rev

Am J Obstet Gynecol

Lancet

Making a difference in countries: strategic approach to improving maternal and newborn survival and health

The development of psychopathology: nature and nurture

Obstetric complications and schizophrenia: a meta-analysis

Br J Psychiatry

Prenatal factors and adult mental and physical health

Can J Psychiatry

World Health Report: 2001: mental health: new understanding, new hope

The definition of pre-eclampsia

Br J Obstet Gynaecol

Original article
Hypertensive Diseases of Pregnancy and the Development of Behavioral Problems in Childhood and Adolescence: The Western Australian Pregnancy Cohort Study