Pubarche and Gonadarche Onset and Progression Are Differently Associated With Birth Weight and Infancy Growth Patterns

Context: Controversy exists regarding associations between early-life growth patterns and timing of puberty.Objective: This work aims to investigate associations between birth anthropometry, early growth patterns, and onset/progression of pubertal milestones in boys and girls.Methods: Among children examined at birth (1997-2003) and at age 36 months in a mother-child cohort, pubertal Tanner stages (B1-5, PH1-5, G1-5) and testicular volume were examined by trained physicians at 1 to 5 follow-up examinations during childhood and adolescence (672 girls and 846 boys, 2006-2013). With parametric survival models we analyzed associations between birth weight, changes in SD scores (SDS) from birth to 36 months (Delta SDS 0-36 > 0.67 SD defining catch-up growth), and age at pubertal onset/attainment of late pubertal stages/menarche.Results: A 1-kg higher birth weight was associated with earlier onset of B2+ (thelarche): -3.9 months (CI, -6.7 to -1.1 months), G2+ (gonadarche): -2.7 months (-5.3 to -0.1 months), Tvol3+ (testis size > 3 mL): -2.8 months (CI, -4.9 to -0.7 months), but with later G4+ and PH4+ in boys, and a slower progression from B2 to menarche (5.3 months [CI, 1.2 to 9.4 months)) in girls. Catch-up growth was associated with earlier PH2+ (pubarche) in girls (-4.1 months [CI, -7.6 to -0.6 months]), earlier PH2+ in boys (-3.4 months [CI, -6.6 to -0.2 months]), faster progression from B2 to menarche in girls (-9.1 months [CI, 14.6 to 3.5 months]), and earlier G4+ and PH4+ in boys.Conclusion: Associations between birthweight and infancy catch-up growth differed for gonadarche and pubarche, and for early and late pubertal markers, with similar patterns in both sexes.</p

Prenatal Triclosan Exposure and Anthropometric Measures Including Anogenital Distance in Danish Infants

BACKGROUND: Triclosan (TCS) is widely used as an antibacterial agent in consumer products such as hand soap and toothpaste, and human exposure is widespread. TCS is suspected of having endocrine-disrupting properties, but few human studies have examined the developmental effects of prenatal TCS exposure. OBJECTIVES: We prospectively examined associations between prenatal TCS exposure and anthropometric measures at birth and anogenital distance (AGD) at 3 months of age. METHODS: Pregnant women from the Odense Child Cohort (n = 514) provided urine samples at approximately gestational week 28 (median 28.7 weeks, range 26.4–34.0), and urinary TCS concentration was measured by isotope dilution TurboFlow–liquid chromatography–tandem mass spectrometry. Multiple linear regression analysis was used to examine associations between prenatal TCS exposure and measures of size at birth (birth weight, length, head and abdominal circumference) and AGD at 3 months of age (median 3.3 months, range 2.3–6.7 months), controlling for potential confounders. RESULTS: Newborn boys in the highest quartile of prenatal TCS exposure had a 0.7-cm [95% confidence interval (CI): –1.2, –0.1, p = 0.01] smaller head circumference than boys in the lowest quartile. Additionally in boys, inverse associations of borderline statistical significance were observed between prenatal TCS exposure and abdominal circumference at birth and AGD at 3 months of age (p-values < 0.10). Prenatal TCS exposure was not significantly associated with any of the outcomes in girls. However, AGD was measured in fewer girls, and we observed no significant interactions between a child’s sex and prenatal TCS exposure in anthropometric measures at birth. CONCLUSION: Prenatal TCS exposure was associated with reduced head and abdominal circumference at birth and with reduced AGD at 3 months of age in boys, although the last two findings were statistically nonsignificant. These findings require replication but are compatible with an anti-androgenic effect of prenatal TCS exposure on fetal growth in boys. CITATION: Lassen TH, Frederiksen H, Kyhl HB, Swan SH, Main KM, Andersson AM, Lind DV, Husby S, Wohlfahrt-Veje C, Skakkebæk NE, Jensen TK. 2016. Prenatal triclosan exposure and anthropometric measures including anogenital distance in Danish infants. Environ Health Perspect 124:1261–1268; http://dx.doi.org/10.1289/ehp.140963

Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

Background: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. Methods: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. Results: Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. Conclusion: Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele

Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study

Background: Endocrine disrupting chemicals have been hypothesized to play a role in the obesity epidemic. Long-term effects of prenatal exposure to non-persistent pesticides on body composition have so far not been investigated. The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function. Methods: In a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n = 203) and at 6 to11 years of age (n = 177) the children underwent a clinical examination and blood sampling for analysis of IGF-I, IGFBP3 and thyroid hormones. Body fat percentage at age 6 to11 years was calculated from skin fold measurements. Pesticide related associations were tested by linear multiple regression analysis, adjusting for relevant confounders. Results: Compared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children: -173 g (-322; -23), -4.8% (-9.0; -0.7) and medium exposed children: -139 g (-272; -6), -3.6% (-7.2; -0.0). Exposed (medium and highly together) children had significantly larger increase in BMI Z-score (0.55 SD (95% CI: 0.1; 1.0) from birth to school age) and highly exposed children had 15.8% (0.2; 34.6) larger skin folds and higher body fat percentage compared to unexposed. If prenatally exposed to both pesticides and maternal smoking (any amount), the sum of four skin folds was 46.9% (95% CI: 8.1; 99.5) and body fat percentage 29.1% (95% CI: 3.0; 61.4) higher. There were subtle associations between exposure and TSH Z-score -0.66(-1.287; -0.022) and IGF-I Z-score (girls: -0.62(-1.0; -0.22), boys: 0.38(-0.03; 0.79)), but not IGFBP3. Conclusions: Occupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to combinations of modern, non-persistent pesticides during early pregnancy was associated with affected growth, both prenatally and postnatally. We found a biphasic association with lower weight at birth followed by increased body fat accumulation from birth to school age. We cannot rule out some residual confounding due to differences in social class, although this was adjusted for. Associations were stronger in highly exposed than in medium exposed children, and effects on body fat content at school age was potentiated by maternal smoking in pregnancy

Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age

Prenatal exposure to pesticides may affect neurodevelopment, but the impact of modern pesticides is unclear. During 1997-2001, women working in greenhouse horticultures were recruited in the beginning of their pregnancy. Based on detailed interview of the women and their employers, those categorized as occupationally exposed to pesticides were moved to unexposed work functions or went on paid leave, while women without any exposure were considered unexposed controls. Of the resulting birth cohort of 203 children, 133 (65%) were examined at age 6-to-11 years together with 44 newly recruited children of same age whose mothers were not occupationally exposed to pesticides in pregnancy. All children underwent a standardized examination including a battery of neurodevelopmental tests. Maternal occupational pesticide exposure in early pregnancy was associated with prolonged brainstem auditory evoked potential latencies in the children as a whole and with impaired neuropsychological function in girls, while no effect was apparent in boys. In girls, language and motor speed functions were significantly inversely associated with prenatal exposure, and a non-significant tendency toward decreased function was also seen for other neuropsychological outcomes. A structural equation model that combined all these test results showed an overall impaired neuropsychological function in girls prenatally exposed to pesticides. Thus, our findings suggest an adverse effect of maternal occupational pesticide exposure on their children’s neurodevelopment, despite the fact that the exposures occurred only during early pregnancy and at well regulated working conditions, where special measures to protect pregnant women were applied