Associations of gestational exposure to air pollution with maternal vitamin D levels: a meta-analysis.

OBJECTIVE: Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce. We investigated the association between air pollution during pregnancy and maternal vitamin D levels. METHODS: A total of 15,935 pregnant women from 5 birth cohorts in Europe and U.S were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants' residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception. RESULTS: We found an association between PM2.5 and higher odds of suboptimal vitamin D levels (i.e., below 20 ng/mL) (odds ratio per 5 µg/m3 increase in PM2.5, 1.43 95%CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels. CONCLUSIONS: PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.

Prenatal and child vitamin D levels and allergy and asthma in childhood.

BACKGROUND: Early-life vitamin D deficiency may impair immune system development contributing to allergy and asthma onset. Findings from prospective studies are inconsistent. OBJECTIVE: To examine whether maternal and child vitamin D levels are associated with allergic and asthma-related symptoms throughout childhood in a Spanish birth cohort. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) levels were measured in the serum of pregnant women (N = 2525) and children (N = 803). Information on allergic and asthma-related symptoms was obtained from repeated questionnaires from 1 to 9 years. RESULTS: A total of 19% of mothers and 24% of children had deficient 25(OH)D3 levels (<20 ng/ml). Higher child 25(OH)D3 levels at 4 years were associated with lower odds of atopic eczema from 4 to 9 years (adjusted odds ratio = 0.90; 95% CI = 0.84-0.97 per 5 ng/ml). Higher maternal and child 25(OH)D3 levels were associated with a lower prevalence of late-onset wheezing at the limit of statistical significance (adjusted relative risk ratio (RRRadj) = 0.86; 95% CI = 0.74-1.00 and RRRadj = 0.76; 95% CI = 0.58-1.02 per 5 ng/ml, respectively). All the remaining associations were null. CONCLUSION: Child 25(OH)D3 levels at pre-school age are associated with a reduced odds of atopic eczema in later childhood and both maternal and child levels may reduce the prevalence of late-onset wheezing. IMPACT: In this Spanish birth cohort, with a total of 19% of mothers and 24% of children with deficient levels of vitamin D, higher child vitamin D at 4 years of age was associated with reduced odds of atopic eczema up to 9 years. There was also some evidence that higher maternal and child vitamin D levels reduced the prevalence of late-onset wheezing. Although these findings need replication, they may imply optimal vitamin D levels at pre-school age to prevent atopic eczema.

Serum concentrations of persistent organic pollutants mixture during pregnancy and anogenital distance in 8-year-old children from the INMA-Asturias cohort.

BACKGROUND: During pregnancy, women are commonly exposed to several endocrine-disrupting chemicals, including persistent organic pollutants (POPs). These compounds can transfer to the fetus through the placenta. Prenatal POP exposure is related to altered fetal genital and reproductive tract development. However, the relationship between exposure to POP mixtures and anogenital distance (AGD) is poorly investigated. This study investigated the association between prenatal exposure to POP mixtures and AGD in 8-year-old children. METHODS: Data were collected from the INMA-Asturias cohort. Maternal serum POP concentrations were measured during the first trimester of pregnancy. Anoscrotal distance (AGDAS) and anopenile distance (AGDAP) in males and anofourchetal distance (AGDAF) and anoclitoral distance (AGDAC) in females were recorded in 362 8-years-olds. Conventional linear regression, and the novel weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) models were applied to assess the relationships between AGD and POPs exposure stratified by sex. RESULTS: Among males, in the linear regression, b-hexachlorocyclohexane, PCB138, PCB153, and PCB180 were inversely associated with the anogenital index (AGI)AS (-0.06 mm/kg (95% confidence interval [CI]: -0.11, -0.02), -0.07 mm/kg (95% CI: -0.14, -0.01), -0.07 mm/kg (95% CI: -0.13, -0.01), and -0.08 mm/kg (95% CI: -0.14, -0.02), respectively). Among females, polybrominated diphenyl ether (PBDE)47 and PBDE154 were positively associated with increased AGIAF (0.02 mm/kg (95% CI: 0.00, 0.03) and 0.09 mm/kg (95% CI: 0.01, 0.17), respectively). BKMR confirmed these associations. WQSR found a negative combined effect of the POP mixture on AGD, and PCB138, PCB153, and PCB180 (weighted 0.18, 0.13, and 0.09, respectively) were identified as the most impacting chemicals. In females, WQSR found a positive combined effect and determined PBDE47 (weighted 0.35) as the most impacting. CONCLUSIONS: Maternal exposure to a POP mixture was negatively associated with AGD in male children and positively associated with AGD in female children, thus providing evidence of the adverse effects of POPs on genital development.

Household income, fetal size and birth weight: an analysis of eight populations.

BACKGROUND: The age at onset of the association between poverty and poor health is not understood. Our hypothesis was that individuals from highest household income (HI), compared to those with lowest HI, will have increased fetal size in the second and third trimester and birth. METHODS: Second and third trimester fetal ultrasound measurements and birth measurements were obtained from eight cohorts. Results were analysed in cross-sectional two-stage individual patient data (IPD) analyses and also a longitudinal one-stage IPD analysis. RESULTS: The eight cohorts included 21 714 individuals. In the two-stage (cross-sectional) IPD analysis, individuals from the highest HI category compared with those from the lowest HI category had larger head size at birth (mean difference 0.22 z score (0.07, 0.36)), in the third trimester (0.25 (0.16, 0.33)) and second trimester (0.11 (0.02, 0.19)). Weight was higher at birth in the highest HI category. In the one-stage (longitudinal) IPD analysis which included data from six cohorts (n=11 062), head size was larger (mean difference 0.13 (0.03, 0.23)) for individuals in the highest HI compared with lowest category, and this difference became greater between the second trimester and birth. Similarly, in the one-stage IPD, weight was heavier in second highest HI category compared with the lowest (mean difference 0.10 (0 .00, 0.20)) and the difference widened as pregnancy progressed. Length was not linked to HI category in the longitudinal model. CONCLUSIONS: The association between HI, an index of poverty, and fetal size is already present in the second trimester.

Maternal sleep duration and neonate birth weight: A population-based cohort study.

OBJECTIVE: To investigate the association between maternal sleep duration (an important health indicator) and neonate birth weight. METHODS: The study included 2536 mother-neonate pairs of a Spanish birth cohort (2004-2006, INMA project). The exposures were questionnaire-based measures of sleep duration before and during pregnancy. The primary outcome was neonate birth weight score (g) standardized to 40 weeks of gestation. RESULTS: In women sleeping for <7 h/day before pregnancy, each additional hour of sleep increased birth weight score by 44.7 g (P = 0.049) in the minimally adjusted model, although findings were not statistically significant after considering other potential confounders (P > 0.05). However, increasing sleep duration for the group of mothers who slept for more than 9 h/day decreased birth weight score by 39.2 g per additional hour (P = 0.001). Findings were similar after adjusting for several sociodemographic confounders and maternal depression-anxiety clinical history as an intermediate factor. Similar but attenuated associations were observed with sleep duration in the second trimester of pregnancy. CONCLUSION: The relationship between maternal sleep duration before and during pregnancy and neonate birth weight is an inverse U-shaped curve. Excessive sleep duration may adversely affect neonate health through its impact on birth weight.

Novel UGT1A1 Gene Mutations in a Boy with Crigler-Najjar Syndrome Type II.

In this article, we reported a patient with Crigler-Najjar syndrome type II with high-unconjugated bilirubin levels that decreased after phenobarbital treatment. The patient had two novel missense mutations in the UGT1A1 gene and a promoter variant in one allele. One mutation was c.1001T > C, that predicted leucine to proline substitution at position 334 (p.Leu334Pro). The other, c.1139A > G, predicted glutamic acid to glycine replacement at position 380 (p.Glu380Gly). In silico analysis indicated that both mutations are likely pathogenic.

Association between pre/perinatal exposure to POPs and children's anogenital distance at age 4 years: A study from the INMA-Asturias cohort.

BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children. METHODS: Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex. RESULTS: In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß = -0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (ß = -0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 ß = -0.065, 95% CI: -0.096, -0.035, second tertile; ß = -0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (ß = -0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (ß = -0.029, 95% CI: -0.059, -0.000, second tertile; ß = -0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (ß = -0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (ß = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (ß = 0.040, 95% CI: 0.011, 0.069, third tertile). CONCLUSIONS: Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females.

Prenatal Exposure to Persistent Organic Pollutants and Anogenital Distance in Children at 18 Months.

BACKGROUND: Anogenital distance (AGD) is a measure of in utero exposure to hormonally active agents. The aim of the present study was to evaluate the association between prenatal exposure to persistent organic pollutants (POPs) and AGD. METHODS: POP levels were measured in pregnant women, and the AGD was recorded in 43 offspring at 18 months. We used linear regression models to analyze the association between maternal POP exposure and offspring AGD. We defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI = AGD / weight at 18 months [mm/kg]) and included this variable in the regression models. RESULTS: AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and females, respectively. AGI was inversely associated with lipid-adjusted concentrations of PBDE-99 (ß = -0.28, 95% confidence interval [CI]: -0.51, -0.04) and PBDE-153 (ß = -0.61, 95% CI: -1.11, -0.11) in males. We did not find any statistically significant relationship between any POPs and AGI in females. CONCLUSIONS: Environmental exposure to POPs may affect genital development and result in reproductive tract alterations with potentially relevant health consequences in maturity.

[Hypovitaminosis D and associated factors in 4-year old children in northern Spain]. / Hipovitaminosis D y factores asociados a los 4 años en el norte de España.

INTRODUCTION: Vitamin D is an essential prohormone in calcium and phosphorus homeostasis. Recent studies show a high frequency of insufficiency/deficiency of vitamin D in the general population worldwide. Our objective was to estimate the prevalence of circulating vitamin D [25(OH)D3] deficiency and insufficiency in children and examine the associated factors. MATERIAL AND METHODS: A total of 283 children, participants in the cohort INMA-Asturias, were studied. The 25(OH)D3 concentrations were quantified by high performance liquid chromatography. The prevalence of deficiency [25(OH)D3<20 ng/ml] and insufficiency [20-29.9 ng/ml] of vitamin D was estimated. Distribution of 25(OH)D3 for month of extraction of specimen, ingestion, and other factors were analysed. RESULTS: The mean 25(OH)D3 was 20.1 ng/ml (range 2.7-49.8), with 8.8% ≥ 30 ng/ml, 38.5% from 20-20.9 ng/ml, and 52.7%<20 ng/ml. Seasonal variation was found, with lower values in winter. There was no relationship between plasma levels and intake of vitamin D (median 2.7µg/day, range 0.81-12.62), time outdoors (mean 3hours, range: 0:21-6:55), or BMI or gender, but there was one found with the mother's levels during gestation. CONCLUSIONS: There is a high prevalence of vitamin D deficiency/insufficiency in children at 4 years. Solar exposure might not be enough in our region. Healthy children should be encouraged to follow adequate outdoor activities with associated sun exposure. Due the deficit of intake in childhood, recommendations are needed about a varied diet with vitamin D-containing foods in this age group, especially during the winter, and assessing the need of vitamin D supplementation in children at risk.

[Growth hormone treatment in small for gestational age children in Spain]. / Tratamiento con hormona de crecimiento en pequeños para la edad gestacional en España.

INTRODUCTION: Since its approval by the European Medicines Agency, a great number of patients born small for gestational date have received recombinant growth hormone treatment in Spain. The aim of this study is to analyse its outcome in the setting of ordinary clinical practice. METHODS: Information was gathered from the registers of the assessment boards that authorise all growth hormone treatments prescribed in public hospitals in six autonomic communities (regions). RESULTS: Valid data from 974 patients was obtained. All of them complied with criteria established by the European Medicines Agency. Patients in the sample were smaller in length than weight at birth, with their median target height being below 1 standard deviation (SD), and 23% of them had been delivered prematurely. Treatment was started at 7.2±2.8 years (mean±SD). The mean patient height at start was -3.1±0.8 SD. They gained 0.7±0.2 SD in the first year, and 1.2±0.8 SD after two years. Final height was attained by 8% of the sample, reaching -1.4±0.7 SD. CONCLUSIONS: These results are similar to other Spanish and international published studies, and are representative of the current practice in Spain. Despite treatment being started at a late age, adequate growth is observed in the short term and in the final height. Up to a 24% of patients show a poor response in the first year.

[Prevalence of vitamin d deficiency and insuffiency and associated factors in pregnant women of northern Spain]. / Prevalencia de deficiencia e insuficiencia de vitamina D y factores asociados en mujeres embarazadas del norte de España.

BACKGROUND AND OBJECTIVES: The vitamin D deficiency during pregnancy has been associated with adverse events during pregnancy and the postnatal child development. In this study we examined plasma levels of vitamin D [25(OH)D3] and factors associated with plasma deficiency and insufficiency in pregnant women in northern Spain. METHODS: We analyzed data from 453 pregnant women participating in the INMA-Asturias cohort in which was determined 25(OH)D3 by high resolution liquid chromatography.Dietary intake of vitamin D was estimated through a food frequency validated questionnaire. We estimated the prevalence of deficiency [25(OH)D3 <20 ng/ml] and insufficiency [20 to 29.9 ng / ml] of vitamin D and analyzed the distribution of 25(OH)D3 per month extraction and other factors. RESULTS: The mean concentration of 25(OH)D3 was 27.7 ng/ml (range 6.4 to 69.5). 27.4% of pregnant women had deficient levels and 35.3% inssuficient. Levels of 25(OH)D3 were higher in the summer months (median 34.1 ng/ml). There was a higher percentage of deficiency in pregnant women with overweight/obesity (34.5%) and under 25 years (47.8%). The average daily intake of vitamin D was 5.48 mg / day (SD 2.82 range 1.09 to 32.52).Intake during the months of October to May was associated with levels of 25(OH)D3. 8.6% reported taking supplements of vitamin D. CONCLUSIONS: We detected a high proportion of pregnant women with deficient or insufficient vitamin D levels, especially in the months of October to May, in pregnant women with overweight and obesity, and the youngest.

Introducción y objetivos: El déficit de vitamina D durante el embarazo se ha relacionado con sucesos adversos durante la gestación y con el desarrollo infantil postnatal. En este estudio examinamos los niveles plasmáticos de vitamina D [25(OH)D3] y los factores asociados a su deficiencia e insuficiencia plasmática en embarazadas del norte de España. Material y método: Se han analizado los datos de 453 gestantes participantes en la cohorte INMA-Asturias a las que se determinó la 25(OH)D3 mediante cromatografía líquida de alta resolución. Se ha estimado la ingesta dietética de vitamina D mediante un cuestionario de frecuencia alimentaria validado. Se han estimado las prevalencias de deficiencia [25(OH)D3.