Maternal Obesity, Gestational Weight Gain, and Asthma in Offspring

Kristen J. Polinski, MSPH; Jihong Liu, ScD; Nansi S. Boghossian, PhD, MPH; Alexander C. McLain, PhD

Disclosures

Prev Chronic Dis. 2017;14(12):E109 

In This Article

Discussion

Using data from a large, nationally representative birth cohort, we examined longitudinal associations of asthma in early childhood with pre-pregnancy BMI and maternal gestational weight gain. Consistent with previous studies,[14,15,20] we found a modest increased risk of asthma in offspring of obese mothers compared with normal-weight mothers. We also found that pre-pregnancy overweight may have a positive but lesser effect. Consistent with our study, a meta-analysis in 2014 also showed that trends in maternal overweight and childhood risk of asthma were not significant.[7]

Research is sparse on maternal gestational weight gain and asthma in offspring, although at least 2 studies that used categorical data on gestational weight gain showed increased risk of asthma.[14,16] Harpsøe et al found in an adjusted model that extreme-high gestational weight gain (>25 kg), compared with a weight gain of 10 to 15 kg, was significantly associated (adjusted OR, 1.17; 95% CI, 1.02–1.33) with asthma among children aged 7 years.[14] In our study population, the magnitude of association was greater for extreme-high weight gain (adjusted OR, 1.53 [95% CI, 0.99–2.35]) than it was in the study by Harpsøe et al, but the association was not significant. We found significant increased odds of asthma in offspring for low-extreme gestational weight gain (adjusted OR, 1.56 [95% CI, 1.04–2.35], but this association was not significant in the study by Harpsøe et al (adjusted OR, 1.17; 95% CI, 0.94–1.46).[14] For the other 3 measures of gestational weight gain (total gestational weight gain, meeting the 2009 IOM recommendations, and weekly rate of weight gain in the second and third trimesters), we found no significant associations with asthma in offspring.

Several possible factors may explain our results. First, BMI rather than gestational weight gain might more directly influence childhood asthma outcomes. Second, the IOM recommendations are not sensitive to the effects of weight gain that occur at crucial points in fetal development.[19] Third, if a woman gains more than or less than the amount recommended by the IOM in the first trimester, then our gestational weight gain measures (ie, IOM weight gain adequacy ratio and the weekly rate of weight gain in the second and third trimesters) might have errors.[22] Additionally, the IOM's estimates of average weight gain in the first trimester were based on weight gain patterns in the 1980s, which may not accurately apply to our more recent ECLS-B cohort.[22] Fourth, a meta-analysis found that childhood asthma is positively associated with children born before 32 weeks;[23] however, our sample consisted of mostly full-term children (85% born at or after 37 weeks), which may further explain why our findings on gestational weight gain were not significant. Overall, better measures of gestational weight gain are needed to separate the potential effects of gestational weight gain on asthma from the effects of gestational age.

More studies are needed to further explore the underlying biological mechanisms of intrauterine exposures on asthma outcomes in offspring. For example, the influence of gestational weight gain on asthma in offspring may differ by the timing of weight gain; therefore, measuring weight gain at multiple time points during pregnancy may allow investigators to determine which patterns of weight gain might have the most effect, if any. Measures of truncal obesity, rather than BMI, may be more appropriate in capturing data on weight gain during pregnancy. Truncal obesity in pregnant women has been associated with visceral adiposity,[24] which in turn could affect the mother's metabolic profile and subsequently the outcomes of offspring. Gestational weight gain and maternal BMI are believed to influence childhood asthma through nonallergic inflammatory mechanisms; for example, high pre-pregnancy BMI and excessive gestational weight gain, particularly in the second and third trimesters, have been associated with higher levels of cord blood leptin.[25,26] Furthermore, excessive weight gain during pregnancy is a strong predictor for elevated levels of tumor necrosis factor α (TNF-α) in infants, and TNF-α has been associated with asthma by age 9 years.[16] Leptin and TNF-α are cell-signaling proteins known as cytokines that are involved in systemic inflammation. More specifically, leptin is a pro-inflammatory adipokine, a type of cytokine secreted from adipose tissue, and it may have pro-inflammatory effects on the child's airways.[16,27] Another potential mechanism involves the contribution of maternal obesity and excessive gestational weight gain to childhood obesity,[6,28,29] which in turn may have effects on lung function and increase the risk of asthma development.[30]

Strengths of our study include the use of a large, multiethnic, nationally representative population-based cohort that is generalizable to US children born in 2001. We assessed our outcome with a longitudinal design. We included 4 measures of gestational weight gain. To our knowledge, ours is the first study to include the IOM weight gain recommendations in exploring the relationship between gestational weight gain and asthma. The secondary analysis with imputed data for missing covariates replicated our findings.

Our study has limitations. First, our prevalence estimate of asthma likely captures data on related conditions (eg, wheeze), because diagnosis of asthma for children younger than 5 years is imprecise without performing spirometry; however, a similar asthma prevalence was measured in this cohort.[31] As many as 50% to 80% of children with asthma develop recurring bronchitis and symptoms such as wheeze, cough, and trouble breathing before the age of 5 years.[2] Second, pre-pregnancy BMI was calculated by using self-reported data on height and weight; however, maternal report is fairly consistent with direct anthropometric measurements.[32] We accounted for major potential confounders; however, we did not have information about asthma severity, genetic factors, or environmental exposures such as endocrine-disrupting chemicals. Our effect estimates and CIs borderline significance, which may limit the clinical relevance of our findings; however, our findings may have implications for public health given that a high proportion of US women in our study gained weight outside of the range recommended by the IOM and a large number of women entered pregnancy overweight or obese.

Overall, our findings have important public health implications for preventing disease and promoting healthy lifestyle behaviors among mothers during pre-pregnancy. Maternal obesity is a risk factor for multiple pregnancy complications that affect both mother and child. As a modifiable risk factor, pre-pregnancy obesity should be targeted in preconception programs that promote optimal preconception weight and help women achieve and maintain a healthy weight throughout pregnancy. Although no single risk factor can entirely account for childhood asthma, such a prevention strategy may reduce the incidence of early childhood asthma in future generations.

Using data from a large nationally representative US birth cohort, our longitudinal analyses support evidence suggesting that maternal obesity and to a lesser extent overweight can affect the development of early childhood asthma. Gestational weight gain is also hypothesized to partly explain childhood asthma, and we provided evidence to support this for the 2 categories of extreme gestational weight gain. In the population we studied, excessive weight gain as defined by the IOM did not appear to be a risk factor for asthma in offspring, but future studies are needed to confirm these findings. Although a better understanding of the mechanisms of early childhood asthma is needed, our study provides evidence that intrauterine exposures to obesity may have long-term effects on children. Efforts should be made to target preconception care to help women achieve and maintain a healthy pre-pregnancy weight and promote ideal weight gain during pregnancy.

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