Center for Fetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
Environ Health Perspect. 2012 May;120(5):668-73. doi: 10.1289/ehp.1104034. Epub 2012 Feb 3.
Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring.
We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans.
A prospective cohort of 665 Danish pregnant women was recruited in 1988-1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants.
After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years.
Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.
全氟烷基酸是广泛应用于各种工业领域的持久性化合物。其中，全氟辛烷磺酸（PFOA）目前在全球范围内的人类中被检测到。最近一项关于在发育早期低剂量接触 PFOA 的小鼠研究报告称，青春期后雌性后代的体重增加和肥胖生物标志物升高。
我们研究了在青春期后雌性小鼠中发现的体重增加是否可以在人类中复制。
1988-1989 年，我们招募了 665 名丹麦孕妇进行前瞻性队列研究，对其后代进行 20 年随访。在妊娠第 30 周时测量血清中的 PFOA。在随访时记录了后代的体重指数（BMI）和腰围（n=665），并在一部分（n=422）参与者中量化了肥胖生物标志物。
在校正了包括母亲孕前 BMI、吸烟、教育和出生体重在内的混杂因素后，胎儿暴露于 PFOA 与女性后代 20 岁时的人体测量学指标呈正相关，但与男性后代无关。比较母亲 PFOA 浓度最高和最低四分位（中位数：5.8 与 2.3ng/ml）的调整后相对风险，超重或肥胖（BMI≥25kg/m2）的相对风险为 3.1（95%可信区间：1.4，6.9），女性后代的腰围>88cm 的相对风险为 3.0（95%可信区间：1.3，6.8）。这相当于平均 BMI 和腰围分别估计增加 1.6kg/m2（95%可信区间：0.6，2.6）和 4.3cm（95%可信区间：1.4，7.3）。此外，母亲的 PFOA 浓度与女性后代的血清胰岛素和瘦素水平呈正相关，与脂联素水平呈负相关。在男性中也观察到了类似的关联，尽管由于观察次数较少，点估计值不太准确。母体全氟辛烷磺酸（PFOS）、全氟辛烷磺酰胺（PFOSA）和全氟壬酸（PFNA）浓度与 20 岁后代的人体测量学指标无关。
我们关于低剂量发育性接触 PFOA 的影响的研究结果与实验结果一致，表明在 20 岁时雌性后代具有肥胖作用。
