Prenatal exposure to maternal smoking during pregnancy and attention-deficit/hyperactivity disorder in offspring: A meta-analysis

Highlights

• Prenatal exposure to maternal smoking during pregnancy or smoking cessation during first trimester was significantly associated with childhood ADHD.

• Smoking cessation before pregnancy, which was not significantly associated with childhood ADHD, was strongly recommended for female smokers planning to conceive.

• Risk of maternal smoking during pregnancy for childhood ADHD varied across geographic regions.

Abstract

Some large population-based cohort studies highlighted the risk of maternal smoking during pregnancy (MSDP) for children attention-deficit/hyperactivity disorder (ADHD). However, the causality of this association is still controversial. Here we performed a meta-analysis trying to clarify the association between prenatal exposure to MSDP and ADHD in offspring. After publication screening, 27 eligible original articles with a total of 3076173 subjects were included. The results showed that either prenatal exposure to MSDP or smoking cessation during first trimester was significantly associated with childhood ADHD after adjusting for parental psychiatric history and social socioeconomic status. Smoking cessation before pregnancy, which was not significantly associated with childhood ADHD, was strongly recommended for female smokers planning to conceive. Inconsistent results were obtained in the meta-analysis on the risk of maternal passive smoking during pregnancy caused by paternal smoking. We also found that risk of MSDP for childhood ADHD varied across geographic regions.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is reported as the most common neurodevelopmental disorder in children of the United States [1]. According to the data from Centers for Disease Control and Prevention (USA), the morbidity of ADHD in children aged 5–17 years has reached 10.4% during 2013–2015 (https://www.cdc.gov/nchs/fastats/adhd.htm). Typical symptoms related to ADHD include impulsivity, inattention, and hyperactivity [2]. Although this neurodevelopmental disorder develops from childhood, longitudinal studies have confirmed that ADHD symptoms could last to adulthood [3,4]. The tendency of having physical and psychological health problems in probands may lead to poor quality of life and dysfunctional social adaptation, which causes heavy burden for both individuals and the society [5]. Doshi et al. [6] reported that it costed United States $143 billion to $266 billion a year for the health care and education of ADHD patients as well as the lost productivity. Moreover, most of the ADHD patients themselves have significant concomitant neurodevelopmental disorders, which makes ADHD patients hard to treat [7]. Given the severe condition of this public issue, prevention of ADHD is becoming extremely urgent.

It is estimated that over 700000 children exposed to smoking prenatally are born every year in the United States alone, raising considerable concerns about its effects on children [8]. Plenty of studies have identified prenatal smoking exposure as a risk factor for neurodevelopmental disorders, including ADHD [[9], [10], [11], [12]]. Animal studies showed that prenatal nicotine exposure was associated with ADHD symptoms in offspring [13,14]. Some large population-based cohort studies also highlighted the risk of maternal smoking as well as paternal smoking during pregnancy for childhood ADHD [15,16]. However, the causality of this association is still controversial. Some researchers reported very weak effect size or even non-significant association, and doubted that inherited effects and socioeconomic status could be the confounding factors. In addition, smoking status could change due to preparation for conception or recognition of pregnancy in parents, to which researchers didn’t pay much attention. Another problem is as Faraone et al. reported [17], the pooled estimate of ADHD prevalence varied from different geographic locations. It is still not clear whether geographic region plays a role in the etiology of ADHD.

In this study, we systematically searched for relevant original publications and performed a meta-analysis trying to clarify the association between prenatal exposure to maternal smoking during pregnancy (MSDP) and ADHD in offspring. We also employed subgroup analysis to explore the effects of maternal smoking cessation, passive smoking (caused by paternal smoking) and potential confounding factors such as genetic, socioeconomic and geographic factors.