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Maternal smoking, BMI associated with PCOS diagnosis in offspring
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Girls who go on to develop polycystic ovary syndrome are more likely to have mothers with obesity or mothers who smoked during pregnancy vs. girls who did not develop PCOS, according to an analysis of Swedish registry data.
“The etiology of PCOS is multifactorial and not fully understood,” Heiddis Valgeirsdottir, a doctoral student in the department of women’s and children’s health at Uppsala University, Sweden, and colleagues wrote in the study background. “Evidence suggests that both heritable and environmental factors play a role in the pathogenesis of PCOS. ... Obesity and greater weight gain are associated with PCOS, and smoking increases the free androgen index in women with PCOS.”
Valgeirsdottir and colleagues analyzed data from 681,123 girls born between January 1982 and December 1995 who were aged at least 15 years, using data from the Swedish medical birth registry. Data included the height and weight of mothers in the birth registry, enabling the calculation of early pregnancy BMI. Researchers followed the offspring from age 15 to 28 years or to the end of 2010. Researchers assessed maternal height, weight, smoking habits, age at delivery, parity and involuntary childlessness before the index pregnancy, as well as the offspring’s size and gestational age at birth. Researchers used Cox regression analysis to estimate HRs for the association between maternal and newborn characteristics and the risk for a PCOS diagnosis in offspring.
Within the cohort, 3,738 girls (0.54%) were diagnosed with PCOS. Follow-up included 4,516,270 person-years. Girls who developed PCOS more frequently had mothers with high BMI, who smoked during pregnancy, were younger, primiparous and had more years of involuntary childlessness before the index pregnancy vs. girls without a PCOS diagnosis, according to researchers.
The researchers observed a dose-response pattern between maternal BMI and maternal smoking in the index pregnancy and risk for PCOS diagnosis in offspring. Girls who had a mother with obesity (BMI 30 kg/m²) were nearly two times more likely to receive a diagnosis of PCOS vs. girls with mothers without obesity (adjusted HR = 1.97; 95% CI, 1.61-2.41), whereas girls with a mother who smoked during early pregnancy were 1.44 times more likely to receive a diagnosis of PCOS vs. girls with mothers who did not smoke during pregnancy (95% CI, 1.27-1.64). There were no associations observed between maternal age, parity, involuntary childlessness, maternal diabetes or preeclampsia in the index pregnancy and development of PCOS in offspring.
“Maternal smoking has not been previously associated with a risk for PCOS, but it has been associated with decreased levels of reproductive hormones and reduced fertility in adult female offspring,” the researchers wrote. “Smoke-exposed fetal ovaries exhibit a higher density of primordial follicles, reduced germ cell and somatic cell proliferation, and genes important for ovarian development are dysregulated, suggesting that maternal smoking may have direct effects on fetal ovaries.”
The researchers also noted an association between being born small for gestational age and small head circumference for gestational age and risk for PCOS later in life; however, the associations were no longer significant after adjusting for maternal characteristics, according to the researchers. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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