Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls.

BACKGROUND: Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort. METHODS: We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes. RESULTS: Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis. CONCLUSION: These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy.

Impact of phthalate and BPA exposure during in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males.

BACKGROUND: Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort. METHODS: We measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. We measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively. In sensitivity analyses we evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes. RESULTS: Exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings. CONCLUSIONS: Associations between in utero phthalate and BPA exposure and peripubertal measures of male reproductive development are dependent on the timing of that exposure during gestation. These findings suggest that future epidemiological studies relating in utero EDC exposure to pubertal outcomes should consider windows of susceptibility.

Validity of Self-Assessed Sexual Maturation Against Physician Assessments and Hormone Levels.

OBJECTIVE: To compare self-report and physician assessments of sexual maturation against serum hormone markers to evaluate the hypothesis that the validity of self-assessed sexual maturation is underestimated in traditional validation studies. STUDY DESIGN: We adapted a self-assessment instrument that 248 Mexican children and adolescents, aged 8-13 years, completed. The participants were examined by a trained pediatrician and provided fasting blood samples for measurement of reproductive hormones (eg, testosterone, estradiol, sex hormone-binding globulin, inhibin B) and other hormones (eg, C-peptide, insulin-like growth factor 1, leptin, dehydroepiandrosterone sulfate) known to change during adolescence. Spearman correlations (r) were calculated among the average rank of all hormones and self-assessed and physician-assessed Tanner stage. The method of triads was used to assess the validity of self-reports by estimating correlations between self-assessments and true but unobservable sexual maturation based on all available data. Bootstrap sampling was used to construct 95% CIs. RESULTS: The validity of self-reported genitalia staging for boys was modest (r = 0.50; 95% CI, 0.31-0.65) and inferior to physician assessment (r = 0.75; 95% CI, 0.56-0.93). Breast stage was well reported (r = 0.89; 95% CI, 0.79-0.97) and superior to physician assessment (r = 0.80; 95% CI, 0.70-0.89). Pubic hair stage reported by boys (r = 0.91; 95% CI, 0.79-0.99) and girls (r = 0.99; 95% CI, 0.96-1.00) was superior to physician assessment (r = 0.79; 95% CI, 0.57-0.97 and r = 0.91; 95% CI, 0.83-0.97, respectively). CONCLUSION: Self-assessment can be validly used in epidemiologic studies for evaluating sexual maturation in children; however, physician assessment may be necessary for accurate assessment of genitalia development in boys.

In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation.

The age of pubertal onset for girls has declined over past decades. Research suggests that endocrine disrupting chemicals (EDCs) may play a role but exposure at multiple stages of development has not been considered. We examined in utero and peripubertal exposure to bisphenol-A (BPA) and phthalates in relation to serum hormones and sexual maturation among females in a Mexico City birth cohort. We measured phthalate metabolite and BPA concentrations in urine collected from mothers during their third trimester (n=116) and from their female children at ages 8-13 years (n=129). Among girls, we measured concurrent serum hormone concentrations, Tanner stages for breast and pubic hair development, and collected information on menarche onset. We used linear and logistic regression to model associations between in utero and peripubertal measures of exposure with hormones and sexual maturation, respectively, controlling for covariates. An interquartile range (IQR) increase in in utero urinary mono-2-ethylhexyl phthalate (MEHP) was positively associated with 29% (95% CI: 9.2-52.6%) higher dehydroepiandrosterone sulfate (DHEA-S), an early indicator of adrenarche, and 5.3 (95% CI: 1.13-24.9) times higher odds of a Tanner stage >1 for pubic hair development. Similar relationships were observed with other in utero but not peripubertal di-2-ethylhexyl phthalate (DEHP) metabolites. IQR increases in in utero monobenzyl phthalate (MBzP) and monoethyl phthalate (MEP) were associated with 29% and 25% higher serum testosterone concentrations (95% CI: 4.3-59.3; 2.1-54.1), respectively. In addition, we observed suggestive associations between in utero and peripubertal MEP concentrations and increased odds of having undergone menarche, and between peripubertal MnBP concentrations and increased odds of having a Tanner stage >1 for both breast and pubic hair development. BPA was not associated with in utero or peripubertal serum hormones or sexual maturation. Our findings suggest in utero phthalate exposure may impact hormone concentrations during peripubescence and timing of sexual maturation. Efforts to control phthalate exposure during pregnancy should be of high priority.

Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys.

Phthalates and BPA are known endocrine disruptors and exposure in pregnant mothers and children is ubiquitous. We explored the relationship of prenatal and childhood exposures with pubertal onset and sex hormones in boys (ages 8-14). Phthalate metabolites and BPA were measured in maternal 3rd trimester or childhood urine. Sex hormones DHEAS, estradiol, inhibin B, SHBG, and total testosterone were measured in serum. Adrenarche and puberty were assessed by pediatrician. Prenatal exposure to some phthalates was associated with decreased DHEAS and inhibin B levels, and with increased SHBG. Prenatal exposure to most phthalates and BPA was associated with greatly reduced odds of adrenarche (odds ratios [OR]=0.12-0.65) and slightly reduced odds of puberty (OR=0.50-0.98). Childhood exposure was not associated with adrenarche or puberty, but some phthalates and BPA were associated with increased SHBG levels and decreased total and free testosterone levels.

Nuevas perspectivas para un problema antiguo. El trabajo de parto pretérmino / New perspectives to an old trouble. The preterm labor

El parto pretérmino ha sido y continúa siendo uno de los mayores problemas en obstetricia. Es la causa más frecuente de mortalidad neonatal y origina una mortalidad elevada en los productos que sobreviven. La presencia de vaginosis bacteriana y otras infecciones genitales se asocia con aumento en el riesgo de parto pretérmino. Las citoquinas liberan prostaglandinas y han implicadas como causa de actividad uterina. Recientemente, se han desarrollado nuevos métodos para detectar el problema; tales como la ultrasonografía transvaginal y las mediciones de fibronectina fetal a nivel cervical. El atosibán, las citoquinas, el trinitrato de glicerilo y otros medicamentos se han propuesto como nuevos tratamiento y están bajo investigación. Estos fármacos permitirán un tratamiento eficaz con pocos efectos colaterales. La administración prenatal de TRH no se recomienda para uso clínico generalizado. Sin embargo, la aplicación prenatal de corticoesteroides a fetos con riesgo de nacer prematuramente; no solamente reduce el riesgo de síndrome de dificultad respiratoria, sino que disminuye de manera importante la mortalidad por hemorragia intraventricular

Trauma nasal en el recién nacido: valoración en 100 partos / Nasal trauma in newborn babies: study on 100 deliveries

Con el objeto de señalar la importancia del examen nasal neonatal, se evaluaron los recién nacidos de 100 partos consecutivos, en la unidad tocoquirúrgica del hospital ABC, durante un periodo de seis semanas. Se propone un protocolo de examen rinológico externo e interno que puede ser realizado por el personal de pediatría durante la evaluación neonatal rutinaria, con posibilidad de consulta al especialista otorrinolaringólogo, si fuese requerido. De un total de 58 niñas y 42 niños recién nacidos, el 48 por ciento presentó algún hallazgo positivo de trauma nasal. Los bebés se dividieron en tres grupos: nacidos por cesárea, por parto eutócico o por parto distócico. En cada grupo se cuantificaron los hallazgos para comparación. Solamente un caso presentó patología nasal lo suficientemente severa como para requerir reparación. Obviamente, es importante el seguimiento de los niños para determinar la posible repercusión de los hallazgos traumáticos en el crecimiento y desarrollo de la nariz