Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta- analyses

Background
Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors.

Objective
The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity.

Methods
The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed.

Results
In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high.

Conclusion
Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.

Objective.
The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity.

Methods.
The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other.

Results.
In total, 354 and 565 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 613 articles after merging duplicates. The papers included in this systematic review were 31: 18 evaluating prenatal exposure to PFASs, 11 childhood exposure, and 2 both. Overall, results were conflicting, with positive, negative, and null associations. 17 papers were included in meta-analyses (12 prenatal, 3 children, and 2 both). The method implemented for data conversion allowed a suitable comparison of different effect estimates. Meta-analyses evaluating the associations between prenatal exposure to PFOA, PFOS, PFNA, PFHxS, and the outcomes BMI, WC, and Dual-Energy X-ray Absorptiometry (DXA) showed no significant results. Meta-analyses for the associations between childhood exposure to PFASs and the outcomes BMI showed no significant results except for a negative association between PFNA and BMI (pooled estimate from a random effect model: -0.045; 95%CI: -0.087, -0.002), however, more studies are required to confirm the strength of this association.

Conclusion.
To increase the reliability of meta-analyses in environmental epidemiology we suggest the conversion of effect estimates to compare different studies. The pooled evidence of the meta-analyses of the present study suggests that there is no overall association between exposure to PFASs and childhood overweight/obesity.