Prenatal Phthalate Exposure and Child Weight and Adiposity from in Utero to 6 Years of Age

Abstract

Background: Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. Objective: We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3–6 years of age). Methods: Within The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation ( ). We estimated average phthalate metabolite associations with child weight -scores from gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity -scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models. Results: For weight, we observed inverse associations between several phthalate metabolites and birth weight -scores, but no associations were observed with postnatal weight -scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length -scores at birth, but positive associations were observed with BMI -scores at 3–4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length -score [95% confidence interval (CI): , ] and a 0.18-unit increase in 4-years-of-age BMI -score (95% CI: 0.04, 0.32). Discussion: We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3–4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. https://doi.org/10.1289/EHP10077

Midpregnancy Phthalate and Phenol Biomarkers in Relation to Infant Body Composition: The Healthy Start Prospective Cohort

“…recently reported gestational phthalate exposures [MEP (median concentration in ), MBzP (4.5), MCPP (2.0), MBP (9.0), MiBP (6.0), MCOP (15.7), ( )] inversely associated with adiposity -scores at birth (weight-for-length) and positively associated with adiposity -scores (BMI) at 3 and 4 years of age, with slightly higher magnitude of associations in males, in a prospective pregnancy cohort conducted at four U.S. sites with recruitment during 2010–2012. 69 Placing our results into the context of these prior laboratory and epidemiologic studies, midpregnancy phthalate and, to a lesser extent, phenol exposure appears to be influencing adipogenesis in a sex-dependent manner to result in initial decreases in infant fat mass among males. By 5 months of age, we continued to note lower fat mass with increased gestational phthalate and phenol exposure, although these associations were less precise.…”

Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants

“…natal exposure to these excipients may be associated with increased risk of preterm birth and low BW (Ferguson et al, 2014(Ferguson et al, , 2022Welch et al, 2022;Aung et al, 2019;Uldbjerg et al, 2022). Results from studies reporting such risks or relationships should be interpreted with some caution due multiple and variable exposures during gestation, often not optimally designed studies with low statistical power, and not fully understood mechanisms that could explain a possible causal relationship.…”

“…Phthalates are not covalently bound to the device matrix and are easily released for human exposure before being hydrolysed, conjugated and excreted in the urine. Phthalate exposure has been associated with preterm birth and low BW (Ferguson et al, 2014(Ferguson et al, , 2022Welch et al, 2022;Street and Bernasconi, 2020), adverse immune responses (Bornehag and Nanberg, 2010), inflammatory cytokine release (Bolling et al, 2012) and reduced anti-inflammatory signalling, possibly increasing the risk of inflammatory disorders such as bronchopulmonary dysplasia (BPD) (Fischer et al, 2013) and septicaemia (Vetrano et al, 2010). Studies on phthalate exposure in premature infants are rare.…”

Prenatal exposures to phthalates and life events stressors in relation to child behavior at age 4–6: A combined cohort analysis

“…Because phthalates can cross the placenta (and alter the development and function of the placenta itself), they also pose a risk to fetal development ( Bräuner et al, 2022 ; Jensen et al, 2015 ; Seymore et al, 2022 ). Epidemiological studies have reported associations between prenatal phthalate exposure and a range of child outcomes including birth size and postnatal growth trajectories, reproductive development, and respiratory health, among others ( Adgent et al, 2020 ; Bornehag et al, 2015 ; Ferguson et al, 2022 ; Shu et al, 2018 ; Swan et al, 2015 ; van den Dries et al, 2021b ).…”