Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

Bornehag, Carl‐Gustaf; Carlstedt, Fredrik; Jönsson, Bo; Lindh, Christian; Jensen, Tina Kold; Bodin, Anna; Jonsson, Carin; Janson, Staffan; Swan, Shanna H.

doi:10.1289/ehp.1408163

Cited by 228 publications

(159 citation statements)

References 47 publications

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“…The AGDs measured in girls and boys are similar to those obtained in previous studies of infants of similar ages. 18,19 As in previous studies, a significant correlation between infant AGD and weight and height was found. 20 The strongest associations between male AGD measurements and breastfeeding types were seen for FB (Fig.…”

Section: Discussionsupporting

confidence: 84%

Breastfeeding Duration and Anogenital Distance in 2-Year-Old Infants

Ortega-García¹,

Olano-Soler²,

Martínez-Álvarez³

et al. 2016

Breastfeeding Medicine

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Background: The anogenital distance (AGD) is an anthropometric marker determined by exposures to androgens in utero and throughout the first few months of life. Early exposures to endocrine-disrupting chemicals such as phthalates have been significantly associated with shortened AGD in boys. Limited studies have explored phthalate concentrations in breast milk and infant formula. Objective: To explore the associations between breastfeeding duration and AGD measures in infants. Materials and Methods: MALAMA (Medio Ambiente y Lactancia Materna) is a follow-up study of 430 motherchild pairs, from birth to 2 years, from two population-based cohorts in Murcia, Spain. Data were collected through medical visits and telephone surveys from birth to 2 years of age. World Health Organization breastfeeding definitions were used. AGD measurements were assessed in a subsample of 71 boys and 49 girls at the 2-year visit. Descriptive analyses, Pearson correlations, and linear regressions were calculated between AGD and breastfeeding duration. Results: Duration of all types of breastfeeding, especially full breastfeeding (FB), is correlated with AGD measures in boys ( p < 0.05). AGD AS (anoscrotal distance) and AGD AP (anopenile distance) were positively associated with FB (b = 0.004, 95%CI: 0.001-0.007 and b = 0.003, 95%CI: 0.000-0.007, respectively). Conclusions: A positive correlation between AGD in male infants and the duration of breastfeeding is reported. Inversely, early introduction of infant formula could lead to the reduction of AGD in boys.

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Section: Discussionsupporting

confidence: 84%

Breastfeeding Duration and Anogenital Distance in 2-Year-Old Infants

Ortega-García¹,

Olano-Soler²,

Martínez-Álvarez³

et al. 2016

Breastfeeding Medicine

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“…Although some studies have demonstrated an association between pregnancy exposure to phthalates such as DBP and reduced AGD in sons (62,63), more direct studies in vitro (64) or by xenografting (65,66) have shown no effect of DBP/phthalate exposure on steroidogenesis by the fetal human testis. However, our studies were not undertaken to evaluate if DBP exposure is a cause of TDS disorders in humans.…”

Section: )mentioning

confidence: 99%

Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window

Driesche¹,

Kilcoyne²,

Wagner³

et al. 2017

JCI Insight

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“…Diisononyl phthalate is a known replacement for DEHP and has also been found to have antiandrogenic properties in utero in rodent models (18,21). In humans, phthalate exposure during pregnancy is associated with a number of infant and child developmental endpoints that are androgen mediated, including reduced anogenital distance (AGD) (22,23), a measure of fetal androgen exposure, and changes in sex-specific behavior (24,25). Few human studies have examined phthalate exposure and androgen concentrations during gestation; prenatal exposure to DEHP has been negatively associated with free testosterone (FT) and total testosterone (TT) concentrations in pregnancy and in umbilical cord blood (26,27).…”

mentioning

confidence: 99%

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes

Sathyanarayana

Butts

Wang

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third-trimester di-2-ethyl hexyl phthalate exposure and total testosterone (TT) concentrations. Here, we examine earlypregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes. Design:We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment.Results: E1 and E2 concentrations were 15% to 30% higher in relation to 1-unit increases in log monoisobutyl phthalate (MiBP), mono-2-ethyl hexyl phthalate, and mono-2-ethyl-5-oxy-hexyl phthalate concentrations, and E2 was 15% higher in relation to increased log monobenzyl phthalate (MBzP). FT concentrations were 12% lower in relation to 1-unit increases in log mono(carboxynonyl) phthalate (MCNP) and mono-2-ethyl-5-carboxypentyl phthalate concentrations. Higher maternal FT was associated with a 25% lower prevalence of having a male genital abnormality at birth. Conclusions:The positive relationships between MiBP, MBzP, and DEHP metabolites and E1/E2 are unique and suggest a positive estrogenic effect in early pregnancy. The inverse relationship between MCNP and DEHP metabolites and serum FT supports previous work examining phthalate/testosterone relationships later in pregnancy. Higher FT in relation to a 25% lower prevalence of male genital abnormalities confirms the importance of testosterone in early fetal development. Abbreviations: AGD, anogenital distance; AGD AC , anoclitoral distance; AGD AF , anofourchette distance; AGD AP , anopenile distance; AGD AS , anoscrotal distance; BBzP, benzyl butyl phthalate; CDC, Centers for Disease Control and Prevention; CI, confidence interval; DBP, dibutyl phthalate; DEHP, di-2-ethyl hexyl phthalate; EDC, endocrine-disrupting chemical; FT, free testosterone; HPLC, high-performance liquid chromatography; LC, liquid chromatography; LOD, limit of detection; MBP, monobutyl phthalate; MBzP, monobenzyl phthalate; MCNP, mono(carboxynonyl) phthalate; MCOP, mono(carboxy-isooctyl) phthalate; MECPP, mono-2-ethyl-5-carboxypentyl phthalate; MEHP, mono-2-ethylhexyl phthalate; MEHHP, mono-2-ethyl-5-hydroxy-hexyl phthalate; MEOHP, mono-2-ethyl-5-oxy-hexyl phthalate; MEP, monoethyl phthalate; MiBP, monoisobutyl phthalate; MS/MS, tandem mass spectrometry; SD, standard deviation; SHBG, sex hormone-binding globulin; TIDES, The Infant Development and the Environment Study; TT, total testosterone. 1870https://academic.oup.com/jcem

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Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys

Cited by 228 publications

References 47 publications

Breastfeeding Duration and Anogenital Distance in 2-Year-Old Infants

Breastfeeding Duration and Anogenital Distance in 2-Year-Old Infants

Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window

Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes

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