153 research outputs found
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Long-term Healthcare of People with Disorders of Sex Development: Predictors of Pubertal Outcomes of Partial Androgen Insensitivity Syndrome - Authors' Reply.
10.1016/j.ebiom.2018.10.035EBioMedicine373
Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.
It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (β' = 0.078 (0.024-0.133); p = 0.005), head circumference (β' = 0.060 (0.012-0.107); p = 0.02), body mass index (β' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (β' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM
The association between age at menarche and later risk of gestational diabetes is mediated by insulin resistance.
AIMS: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy. METHODS: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy. RESULTS: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10-4; quadratic term: p = 1.0 × 10-3; n = 889; overall model p = 8.1 × 10-3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = -0.13, p = 5.2 × 10-4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = -0.11, p = 2.8 × 10-3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771). CONCLUSIONS: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance.Funding for this study has come from the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (RG1644). Other core funding has come from the Medical Research Council (7500001180, G1001995, U106179472), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. KO is supported by the Medical Research Council (Unit Programme number: MC_UU_12015/2)
Age at Weaning and Infant Growth: Primary Analysis and Systematic Review.
OBJECTIVE: To test whether earlier age at weaning (age 3-6 months) may promote faster growth during infancy. STUDY DESIGN: Weaning at age 3.0-7.0 months was reported by 571 mothers of term singletons in a prospective birth cohort study conducted in Cambridge, UK. Infant weight and length were measured at birth and at age 3 months and 12 months. Anthropometric values were transformed into age- and sex-adjusted z-scores. Three linear regression models were performed, including adjustment for confounders in a stepwise manner. Measurements at age 3 months, before weaning, were used to consider reverse causality. RESULTS: Almost three-quarters (72.9%) of infants were weaned before age 6 months. Age at weaning of 3.0-7.0 months was inversely associated with weight and length (but not with body mass index) at 12 months (both P ≤ .01, adjusted for maternal and demographic factors). These associations were attenuated after adjustment for type of milk feeding and weight or length at age 3 months (before weaning). Rapid weight gain between 0 and 3 months predicted subsequent earlier age at weaning (P = .01). Our systematic review identified 2 trials, both reporting null effects of age at weaning on growth, and 15 observational studies, with 10 reporting an inverse association between age at weaning and infant growth and 4 reporting evidence of reverse causality. CONCLUSION: In high-income countries, weaning between 3 and 6 months appears to have a neutral effect on infant growth. Inverse associations are likely related to reverse causality.European Union, World Cancer Research Foundation International, Medical Research Council, Newlife Foundation, NIHR Cambridge Comprehensive Biomedical Research Center, and University of California San Francisco Pathways Explore GrantThis is the final version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0022347615004710
The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth
Abstract
Objective
Previously we found that certain fetal imprinted genes represented as an allele score are associated with maternal pregnancy glucose concentrations. Recently it was reported that fetal polymorphisms with strong associations with birth weight tend to mediate these independently of increases in maternal pregnancy glucose concentrations. We therefore investigated whether potential associations between the fetal allele score and birth weight were related to maternal glucose concentrations in the Cambridge Baby Growth Study.
Results
The fetal imprinted gene allele score was positively associated with birth weight (β = 63 (17–109) g/risk allele, β′ = 0.113, p = 7.6 × 10−3, n = 405). This association was partially attenuated by adjusting for maternal glucose concentrations (β = 50 (4–95) g/risk allele, β′ = 0.089, p = 0.03, n = 405). The allele score was also positively associated with risk of being large for gestational age at birth (odds ratio 1.60 (1.19–2.15) per risk allele, p = 2.1 × 10−3, n = 660) and negatively associated with risk of being small for gestational age at birth (odds ratio 0.65 (0.44–0.96) per risk allele, p = 0.03, n = 660). The large for gestational age at birth association was also partially attenuated by maternal glucose concentrations. These results suggest that associations between the fetal imprinted gene allele score and size at birth are mediated through both glucose-dependent and glucose-independent mechanisms
Anogenital distance from birth to 2 years: a population study.
BACKGROUND: Anogenital distance (AGD) is sexually dimorphic in rodents and humans, being 2- to 2.5-fold greater in males. It is a reliable marker of androgen and antiandrogen effects in rodent reproductive toxicologic studies. Data on AGD in humans are sparse, with no longitudinal data collected during infancy. OBJECTIVE: This study was designed to determine AGD from birth to 2 years in males and females and relate this to other anthropometric measures. MATERIALS AND METHODS: Infants were recruited from the Cambridge Baby Growth Study. AGD was measured from the center of the anus to the base of the scrotum in males and to the posterior fourchette in females. Measurements were performed at birth and at 3, 12, 18, and 24 months of age. RESULTS: Data included 2,168 longitudinal AGD measurements from 463 male and 426 female full-term infants (median = 2 measurements per infant). Mean AGD (+/- SD) at birth was 19.8 +/- 6.1 mm in males and 9.1 +/- 2.8 mm in females (p < 0.0001). AGD increased up to 12 months in both sexes and in a sex-dimorphic pattern. AGD was positively correlated with penile length at birth (r = 0.18, p = 0.003) and the increase in AGD from birth to 3 months was correlated with penile growth (r = 0.20, p = 0.001). CONCLUSION: We report novel, longitudinal data for AGD during infancy in a large U.K. birth cohort. AGD was sex dimorphic at all ages studied. The availability of normative data provides a means of utilizing this biological marker of androgen action in population studies of the effects of environmental chemicals on genital development
Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.
The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development.We thank the participating families and the Cambridge Baby Growth Study team. Data were presented at Erasmus Medical Centre, Rotterdam, where suggestions were integrated into analyses. The study was supported by the European Union Fifth Framework Programme) (Grant #QLK4-CT-1999-01422, World Cancer Research Fund International, Mothercare Foundation, Newlife Foundation for Disabled Children and Medical Research Council (UK). We also thank the Wellcome Trust Clinical Research Facility and the National Institute for Health Research — Biomedical Research Centre Cambridge.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0018506X15000033#
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Increased Cross-Gender Identification Independent of Gender Role Behavior in Girls with Congenital Adrenal Hyperplasia: Results from a Standardized Assessment of 4- to 11-Year-Old Children.
While reports showing a link between prenatal androgen exposure and human gender role behavior are consistent and the effects are robust, associations to gender identity or cross-gender identification are less clear. The aim of the current study was to investigate potential cross-gender identification in girls exposed prenatally to high concentrations of androgens due to classical congenital adrenal hyperplasia (CAH). Assessment included two standardized measures and a short parent interview assessing frequency of behavioral features of cross-gender identification as conceptualized in Part A of the diagnostic criteria for gender identity disorder (GID) in the DSM-IV-TR. Next, because existing measures may have conflated gender role behavior with gender identity and because the distinction is potentially informative, we factor analyzed items from the measures which included both gender identity and gender role items to establish the independence of the two constructs. Participants were 43 girls and 38 boys with CAH and 41 unaffected female and 31 unaffected male relatives, aged 4- to 11-years. Girls with CAH had more cross-gender responses than female controls on all three measures of cross-gender identification as well as on a composite measure of gender identity independent of gender role behavior. Furthermore, parent report indicated that 5/39 (12.8 %) of the girls with CAH exhibited cross-gender behavior in all five behavioral domains which comprise the cross-gender identification component of GID compared to 0/105 (0.0 %) of the children in the other three groups combined. These data suggest that girls exposed to high concentrations of androgens prenatally are more likely to show cross-gender identification than girls without CAH or boys with and without CAH. Our findings suggest that prenatal androgen exposure could play a role in gender identity development in healthy children, and may be relevant to gender assignment in cases of prenatal hormone disruption, including, in particular, cases of severely virilized 46, XX CAH.The study was supported by USPHS grant HD24542 to Melissa Hines and by funds from Cambridge University, Cambridge, UK.This is the accepted manuscript version. The final version is available from Springer at http://link.springer.com/article/10.1007%2Fs10508-014-0385-0
Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour.
Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender-related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development.This is the author accepted manuscript. The final version is available from Royal Society Publishing via http://dx.doi.org/10.1098/rstb.2015.012
Ultrasound estimates of visceral and subcutaneous-abdominal adipose tissues in infancy.
Other imaging techniques to quantify internal-abdominal adiposity (IA-AT) and subcutaneous-abdominal adiposity (SCA-AT) are frequently impractical in infants. The aim of this study was twofold: (a) to validate ultrasound (US) visceral and subcutaneous-abdominal depths in assessing IA-AT and SCA-AT from MRI as the reference method in infants and (b) to analyze the association between US abdominal adiposity and anthropometric measures at ages 3 months and 12 months. Twenty-two infants underwent MRI and US measures of abdominal adiposity. Abdominal US parameters and anthropometric variables were assessed in the Cambridge Baby Growth Study (CBGS), n = 487 infants (23 girls) at age 3 months and n = 495 infants (237 girls) at 12 months. US visceral and subcutaneous-abdominal depths correlated with MRI quantified IA-AT (r = 0.48, P < 0.05) and SCA-AT (r = 0.71, P < 0.001) volumes, respectively. In CBGS, mean US-visceral depths increased by ~20 % between ages 3 and 12 months (P < 0.0001) and at both ages were lower in infants breast-fed at 3 months than in other infants. US-visceral depths at both 3 and 12 months were inversely related to skinfold thickness at birth (P = 0.03 and P = 0.009 at 3 and 12 months, resp.; adjusted for current skinfold thickness). In contrast, US-subcutaneous-abdominal depth at 3 months was positively related to skinfold thickness at birth (P = 0.004). US measures can rank infants with higher or lower IA-AT and SCA-AT. Contrasting patterns of association with visceral and subcutaneous-abdominal adiposities indicate that they may be differentially regulated in infancy
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