Maternal pre-pregnancy overweight/obesity and the risk of attention-deficit/hyperactivity disorder in offspring: a systematic review, meta-analysis and quasi-experimental family-based study

Abstract

Background Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden. Methods We searched PubMed, Embase and PsycINFO during 1975–2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding. Results Eight cohorts with a total of 784 804 mother–child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25–1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84–2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28–1.34), HRobesity = 1.92 (1.87–1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19–1.25), HRobesity = 1.60 (1.55–1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98–1.23), HRobesity = 1.44 (1.22–1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92–1.11), HRobesity = 1.10 (0.94–1.27)]. Conclusion Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

“…Additionally, studies that evaluate subjective depressive and stress symptoms are prone to recall and reporting bias thus skewing results. Dose-dependent effects of obesity and smoking have been demonstrated in studies 9,39,59 . However, population-based assessment of the severity of asthma, autoimmune disease, and depression in pregnancy is challenging, and may require surrogate markers including hospitalization stay or medication use.…”

“…4, Supplementary Fig. 2 39 ) suggesting a dose-dependent increase in risk 10,40 . Findings relating gestational diabetes and ADHD in offspring were mixed, but pre-eclampsia showed increased odds of ADHD 17,41,42 (Supplementary Table 4).…”

The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials

“…Etiological research outlines that ADHD constitutes a complex condition with multiple interactive factors [9]. Specific causes of the disorder are yet to be determined, but various contributing risk factors have been identified, including genetics [10][11][12][13], epigenetics [14,15], problems during pregnancy (such as stress, substance use, and other mental and physical diseases) [16][17][18], premature birth [19,20], obstetric and neonatal complications [21][22][23][24], and infections [25,26]. Neuropsychological mechanisms have also been identified in the onset and course of ADHD, such as brain injuries [27], neuroanatomical substrates related with genuine motor dysfunction [28] and deficient decision-making [29].…”

Maternal pre-pregnancy body mass index and mental health problems in early adolescents from the 2004 Pelotas birth cohort

“…In addition, they were more likely to need speech-language therapy, psychological services, and any special needs service compared with children of normal weight mothers 10 . Others have reported associations between maternal pre-pregnancy obesity and lower cognitive performance 18 , intellectual disability 19 , 20 , ADHD 21 , and autism 22 . Although the specific outcomes differed, the findings are generally consistent with those observed in our study.…”