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Leon Speroff Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland
Dr. Jensen reports he is a consultant for and receives grant/research support from Bayer, Merck, ContraMed, and FHI360; he receives grant/research support from Abbvie, HRA Pharma, Medicines 360, and Conrad; and he is a consultant for the Population Council.
SYNOPSIS: Results from a 25-year prospective study demonstrate a moderate association between childhood obesity before age 12 years and female infertility in adulthood.
SOURCE: He Y, Tian J, Oddy WH, et al. Association of childhood obesity with female infertility in adulthood: A 25-year follow-up study. Fertil Steril 2018;110:596-604.
To examine the association between childhood obesity and infertility in adulthood, He et al used a large population-based prospective database from Australia. In 1985, researchers enrolled 8,498 children (4,191 girls) in the Australian Schools Health and Fitness Survey (ASHFS), a nationally representative sample of Australian school children between 7 and 15 years of age. All of these children had physical assessments (body mass index [BMI], waist-to-height ratio). Those 9 to 15 years of age completed questionnaires evaluating lifestyle and cardiovascular risk factors.1 To better evaluate how health and fitness in childhood affect the development of disease during adulthood, the authors of the Childhood Determinants of Adult Health (CDAH) study took advantage of this large database. From 2002-2004, researchers traced 3,412 female former participants (then 26-36 years of age) from the ASHFS; 2,734 women agreed to participate in the CDAH study and received questionnaires from 2004-2006 (CDAH1) and 2009-2011 (CDAH2). Adult weight and height were measured in clinics during CDAH1, and participants also provided self-reported measurements that allowed investigators to calculate a correction factor. During CDAH2, weight was self-reported only.
A total of 1,754 women provided details on reproductive health questions at least once during CDAH1 or CDAH2. These included detailed questions on female and male infertility. The investigators considered a number of covariate measures, including age at menarche, socioeconomic status, education, smoking, alcohol consumption, and total physical activity as potential confounders. After excluding 210 women missing data on confounders, the final analysis included 1,544 women.
Compared to those with normal childhood weight between the ages of 7 and 11 years, women with childhood obesity were more likely to report infertility (adjusted relative risk [aRR], 2.94; 95% confidence interval [CI], 1.48-5.84), having ever tried to become pregnant without succeeding for > 12 months (aRR 3.89; 95% CI, 1.95-7.77), or having seen a doctor because of trouble becoming pregnant (aRR, 3.65; 95% CI, 1.90-7.02). However, these same associations were not seen among adult women with childhood obesity between the ages of 12 and 15 years. Adult infertility also occurred more commonly among underweight compared to normal-weight girls 7 to 11 years of age. This resulted in a U-shaped association of BMI z scores, with the risk of adult infertility significantly higher among children with z scores > 1.05 or < -0.80. Childhood waist-to-hip ratio at either age grouping also was not associated with infertility.
Based on the results of this prospective study, the authors concluded that among girls, childhood obesity before age 12 years increases the risk of adult infertility.
Although we can’t change our patients’ childhoods, we might influence the way they raise their own children. We live in a world that seems increasingly scary to parents. Most adults my age remember spending large amounts of time playing outside with a pack of neighborhood kids. We also remember physical education class every day in middle and high school. Although few organized sports existed except Little League, physical activity included walking or riding bikes everywhere you needed to go. Today, most parents discourage kids from walking or biking on roads because of heavy traffic (in part caused by the many parents taking kids to and from activities by car). Our digital world also reduces the incentive to go out and experience the real world. High-calorie beverages and foods contribute to childhood obesity. Since adults make decisions about food purchases, it is not surprising that childhood obesity rates have risen with the adult obesity epidemic. Parents of overweight children tend not to perceive them as overweight, but they are sensitive to concerns about future weight-related health risks.2
This study by He et al provides high-quality evidence that early childhood obesity increases the risk of adult infertility. The prospective nature of the study, and adjustment for confounders, allows for the calculation of infertility incidence and relative risks. Unlike so many studies with weak associations (e.g., risk estimates < 2.0), all of the adjusted RRs in this study for obesity in girls younger than 12 years of age hovered around 3.0, indicating a moderate association. Those women who remained consistently obese from 12 years and younger through adulthood had a significantly higher risk of infertility than those who consistently maintained normal body weight. The authors also found that childhood BMI before age 12 years and the risk of adult infertility followed a U-shaped curve, with higher rates of infertility at both extremes. A 2007 study reported a similar U-shaped curve with adolescent BMI and fertility in Finland.3
How might early childhood obesity influence adult infertility? Female rats fed an obesogenic diet from weaning developed a reduced number of oocytes and preantral follicles and did not show preovulatory progesterone and luteinizing hormone surges.4 Studies in humans have shown early-onset obesity associated with early puberty and abnormal maturation of the hypothalamic-pituitary-ovarian axis.5 These changes may lead to the development of polycystic ovarian syndrome. Once cyclicity begins, the system may be more resilient, as suggested by the lack of association of later onset childhood obesity and infertility in this study.
We live in a society that values diversity and tolerance. This makes us stronger and better. However, this also prevents many of us from commenting on obesity in children out of fear of seeming insensitive. But childhood obesity affects health directly and reduces productivity and longevity. We now have evidence that childhood obesity affects future fertility. Commenting on the health effects of childhood obesity is not insensitive. Your patients’ grandchildren may thank you for getting involved.
Financial Disclosure: OB/GYN Clinical Alert’s Editor Jeffrey T. Jensen, MD, MPH, reports that he is a consultant for and receives grant/ research support from Bayer, Merck, ContraMed, and FHI360; he receives grant/research support from Abbvie, HRA Pharma, Medicines 360, and Conrad; and he is a consultant for the Population Council. Peer Reviewer Catherine Leclair, MD; Nurse Planners Marci Messerle Forbes, RN, FNP, and Andrea O’Donnell, FNP; Editorial Group Manager Terrey L. Hatcher; Executive Editor Leslie Coplin; and Editor Jonathan Springston report no financial relationships relevant to this field of study.