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Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol.

ABSTRACT: INTRODUCTION:Hypertensive disorders of pregnancy (HDPs), that is chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed on chronic hypertension) and white coat hypertension, affect approximately 5%-15% of pregnancies. HDP exposure has been linked to an increased risk of autism spectrum disorder, attention deficit/hyperactivity disorder and other neurodevelopmental disorders in children. However, findings are inconsistent, and a clear consensus on the impact of HDPs on the risk of neurodevelopmental disorders is needed. Therefore, we aim to synthesise the published literature on the relationship between HDPs and the risk of neurodevelopmental disorders in the form of a systematic review and meta-analysis. METHODS AND ANALYSIS:We will include cohort, case-control and cross-sectional studies in which diagnosis of an HDP was reported, and neurodevelopmental disorders were the outcome of interest based on a preprepared protocol. A systematic search of PubMed, CINAHL, Embase, PsycINFO and Web of Science will be conducted in accordance with a detailed search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction using a standardised data collection form and assess study quality using a bias classification tool. Meta-analyses will be performed to calculate overall pooled estimates using the generic inverse variance method. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. ETHICS AND DISSEMINATION:This proposed systematic review and meta-analysis is based on published data, therefore, does not require ethics approval. Findings will be presented at scientific conferences and disseminated through publication in a peer-reviewed journal. REGISTRATION:CRD42017068258.

SUBMITTER: Maher GM

PROVIDER: S-EPMC5640119 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol.

Maher Gillian M GM O'Keeffe Gerard W GW Kenny Louise C LC Kearney Patricia M PM Dinan Ted G TG Khashan Ali S AS

BMJ open 20171005 10

<h4>Introduction</h4>Hypertensive disorders of pregnancy (HDPs), that is chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed on chronic hypertension) and white coat hypertension, affect approximately 5%-15% of pregnancies. HDP exposure has been linked to an increased risk of autism spectrum disorder, attention deficit/hyperactivity disorder and other neurodevelopmental disorders in children. However, findings are inconsistent, and a clear consensus on the impac ...[more]

PMID: 28982838

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Project description:Importance:Although research suggests an association between hypertensive disorders of pregnancy (HDP) and autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders in offspring, consensus is lacking. Given the increasing prevalence of hypertension in pregnancy, it is important to examine the association of HDP with neurodevelopmental outcome. Objective:To synthesize the published literature on the association between HDP and risk of neurodevelopmental disorders in offspring in a systematic review and meta-analysis. Data Sources:On the basis of a preprepared protocol, a systematic search of PubMed, CINAHL, Embase, PsycINFO, and Web of Science was performed from inception through June 7, 2017, supplemented by hand searching of reference lists. Study Selection:Two investigators independently reviewed titles, abstracts, and full-text articles. English-language cohort and case-control studies were included in which HDP and neurodevelopmental disorders were reported. Data Extraction and Synthesis:Data extraction and quality appraisal were performed independently by 2 reviewers. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout. Main Outcomes and Measures:Random-effects meta-analyses of estimated pooled odds ratios (ORs) for HDP and ASD and for HDP and ADHD. Stand-alone estimates were reported for all other neurodevelopmental disorders. Results:Of 1166 studies identified, 61 unique articles met inclusion criteria. Twenty studies reported estimates for ASD. Eleven of these (including 777 518 participants) reported adjusted estimates, with a pooled adjusted OR of 1.35 (95% CI, 1.11-1.64). Ten studies reported estimates for ADHD. Six of these (including 1 395 605 participants) reported adjusted estimates, with a pooled adjusted OR of 1.29 (95% CI, 1.22-1.36). Subgroup analyses according to type of exposure (ie, preeclampsia or other HDP) showed no statistically significant differences for ASD or ADHD. Thirty-one studies met inclusion criteria for all other neurodevelopmental disorders. Individual estimates reported for these were largely inconsistent, with few patterns of association observed. Conclusions and Relevance:Exposure to HDP may be associated with an increase in the risk of ASD and ADHD. These findings highlight the need for greater pediatric surveillance of infants exposed to HDP to allow early intervention that may improve neurodevelopmental outcome.

Project description:INTRODUCTION:Hypertensive disorders of pregnancy (HDP), one of the most common obstetrical complications, has been reported to have a controversial relationship with the increased risk of asthma in offspring. No systematic review of this topic has been performed. The aim of this systematic review will be to summarise the available evidence examining the association between HDP and the risk of asthma in offspring. METHODS AND ANALYSIS:We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. A systematic search of the PubMed, Embase, Cochrane and Web of Science databases will be performed using a detailed search strategy from database inception through 31 December 2019. Cohort, case-control and cross-sectional studies that report a diagnosis of maternal HDP and asthma in offspring will be included. Studies will be limited to the English language and include only human participants. Two independent reviewers will conduct the study selection, data extraction and risk of bias assessments using a standardised data extraction form. A meta-analysis will be performed to calculate overall pooled estimates using the generic inverse variance method. The data will be synthesised by either fixed-effect or random effects models according to heterogeneity tests. All analyses will be performed in Stata 14 and RevMan 5.3. High-quality evidence of the relationship between HDP and the risk of asthma in exposed offspring will be identified through the synthesis of current studies. In addition, the results of subgroup analyses and related secondary outcomes will be reported. The following will be concluded: (i) whether HDP increases the risk of asthma in offspring, (ii) whether HDP affects the severity of asthma in exposed offspring and (iii) whether possible differences in the risk of asthma among different HDP subgroups exist. ETHICS AND DISSEMINATION:There is no requirement for ethics approval because the meta-analysis and systematic review will be based on published data. It is anticipated that the dissemination of results will take place at conferences and through publication in a peer-reviewed journal.

Project description:BACKGROUND:In the last 2 decades, several studies have examined the association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children and shown conflicting results. AIM:This systematic review aimed to assess the evidence for an association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children. We also sought to assess whether levothyroxine treatment for maternal thyroid hormone insufficiency improves child neurodevelopment outcomes. METHODS:We performed systematic literature searches in MEDLINE, EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit, Grey Source and Open Grey (latest search: March 2017). We also conducted targeted web searching and performed forwards and backwards citation chasing. Meta-analyses of eligible studies were carried out using the random-effects model. RESULTS:We identified 39 eligible articles (37 observational studies and 2 randomized controlled trials [RCT]). Meta-analysis showed that maternal subclinical hypothyroidism and hypothyroxinaemia are associated with indicators of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04, respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not associated with attention deficit hyperactivity disorder, and their effect on the risk of autism in offspring was unclear. Meta-analysis of RCTs showed no evidence that levothyroxine treatment for maternal hypothyroxinaemia or subclinical hypothyroidism reduces the incidence of low intelligence quotient in offspring. LIMITATIONS:Although studies were generally of good quality, there was evidence of heterogeneity between the included observational studies (I2 72%-79%). CONCLUSION:Maternal hypothyroxinaemia and subclinical hypothyroidism may be associated with intellectual disability in offspring. Currently, there is no evidence that levothyroxine treatment, when initiated 8- to 20-week gestation (mostly between 12 and 17 weeks), for mild maternal thyroid hormone insufficiency during pregnancy reduces intellectual disability in offspring.

Project description:ImportanceHypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.ObjectiveTo investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.Design, setting, and participantsThis Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.ExposuresDiagnoses of HDP, which were provided by the Medical Birth Register.Main outcomes and measuresDiagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.ResultsThe study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, -0.10; 95% CI, -0.13 to -0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, -0.09 to 0.08).Conclusions and relevanceThe study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.

Project description:BackgroundHypertensive disorders during pregnancy (HDP), including gestational hypertension, preeclampsia (PE), and chronic hypertension, affect approximately 10% of pregnancies worldwide. PE was associated with elevated blood pressure (BP) in the offspring confirmed by previous literature. No previous systematic review has investigated the associations between the subtypes of HDP and BP in offspring. Therefore, from the published literature, the present systematic review and meta-analysis aims to reach to a clear consensus on this topic.MethodsThe Cochrane Handbook for Systematic Reviews of Interventions was used to structure our methodological approach, and the Preferred Reporting Items for Systematic Reviews and Meta Analyses Protocols guidelines to this protocol. We will include cohort, case-control, and cross-sectional studies, in which HDP or its subtypes were reported and BP in the offspring was the outcome of interest. A systematic search of PubMed, Embase, the Cochrane library, and Web of Science will be conducted according to a specific search strategy. The titles and abstracts of all literature will be reviewed independently by 2 authors. A standardized data collection form will be used for data extraction. The overall pooled estimates will be calculated by meta-analysis in Revman 5.3 based on an inverse variance method. According to the heterogeneity by the I, a random-effect model or a fixed-effect model will be chosen to pool data. Risk of bias and quality of the studies will be assessed by a suitable bias classification tool.ResultsThis study will provide high-quality evidence of the effects in offspring BP, which were influenced by different subtypes of HDP.ConclusionThis systematic review will infer a conclusion on the associations between different subtypes of HDP and BP in offspring.Ethics and disseminationDue to the data come from the published study, the present systematic review and meta-analysis does not require ethics approval. Findings will be published in a peer-reviewed journal.RegistrationSupporting data can be found at the International Prospective Register of Systematic Reviews (PROSPERO) website, with registration number CRD 42018110872.

Project description:BackgroundHypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC).MethodsWe identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups.ResultsEighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60-1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20-1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00-6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively).ConclusionsOur meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

Project description:BackgroundFever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis.MethodsPeer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801).ResultsWe finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case-control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12-1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13-95% CI: 1.02-1.26].LimitationsWe excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case-control).ConclusionAdditional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester).

Dataset Information

Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol.

Publications

Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol.

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