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2.
BMC Pediatr ; 19(1): 338, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526385

RESUMO

BACKGROUND: Earlier pubertal timing has been observed in many countries. We aimed to explore if prenatal exposure to maternal obesity, smoking, and alcohol intake was associated with timing of puberty by use of a novel marker of pubertal timing: 'the height difference in standard deviations' (HD:SDS). METHODS: HD:SDS is the difference between pubertal height in standard deviations and adult height in standard deviations, and it correlates well with age at peak height velocity. Pubertal height was measured by health care professionals at approximately 13 years in boys and 11 years in girls, and the children's adult height was predicted from parental height reported by the mothers during pregnancy. Information on HD:SDS was available for 42,849 of 56,641 eligible boys and girls from the Danish National Birth Cohort born 2000-2003. In a subsample, HD:SDS was validated against age at the following self-reported pubertal milestones: Tanner stages, menarche, first ejaculation, voice break, acne, and axillary hair. Prenatal exposures were reported by mothers during pregnancy. RESULTS: HD:SDS correlated moderately with the pubertal milestones considered (correlation coefficients: - 0.20 to - 0.53). With normal weight (body mass index (BMI): 18.5-24.9 kg/m2) as the reference, maternal pre-pregnancy obesity (BMI: 30.0+ kg/m2) was associated with earlier pubertal timing: 0.23 (95% confidence interval (CI): 0.18, 0.28) higher HD:SDS in boys and 0.19 (95% CI, 0.14, 0.24) higher HD:SDS in girls. Maternal smoking was not associated with pubertal timing. Compared to alcohol abstainers, maternal intake of > 3 units of alcohol weekly was associated with later puberty in boys only: 0.14 (95% CI, 0.05, 0.24) lower HD:SDS. CONCLUSION: As correlations between HD:SDS and the considered pubertal milestones were comparable to those reported in the literature between age a peak height velocity and the considered pubertal milestones, the validity of HD:SDS seems acceptable. Maternal pre-pregnancy obesity was associated with earlier pubertal timing in both sexes, and maternal alcohol intake during pregnancy was associated with later pubertal timing in boys. Maternal smoking has been linked to earlier timing of puberty, but this was not replicated in our setting using HD:SDS as a marker of pubertal timing.

3.
J Nutr ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387119

RESUMO

BACKGROUND: Intervention studies have shown that long-chain (LC) n-3 PUFA intake can prolong gestation but the dose-time-effect relations remain unresolved. OBJECTIVES: We examined the effect on gestation duration of 2 doses of supplemental LC n-3 PUFAs. METHODS: We undertook a 3-group parallel randomized controlled trial in areas of China with low (median: 2.1 g/d) and higher (14.3 g/d) fish intake. Unselected women (median: age, 26.2 y; BMI, 20. kg/m2) were randomly assigned at midgestation to take four 0.72-g identical gelatin capsules per day until the last day of the preterm period (<259 days of gestation), when they were asked to stop. Capsules contained fish oil [high fish oil (HFO) group (60% w/w LC n-3 PUFAs)], a 1:3 mixture of fish oil to olive oil [low fish oil (LFO) group (20%)], or olive oil [control (CON) group (0%)], providing 2.0, 0.5, and 0 g/d of LC n-3 PUFAs, respectively. Habitual fish intake was recorded at baseline. Hazard rate ratios (HRRs) for spontaneous delivery <259 days of gestation and <273 days of gestation across groups were estimated by Cox regression. RESULTS: Among 5531 women randomly assigned, 92.5% were included in analyses (1706/1825, 1695/1851, and 1717/1855, respectively). The groups were similar with respect to hazard rates <259 days of gestation [HRR: 1.04 (95% CI: 0.70, 1.53) for LFO compared with CON and 0.90 (95% CI: 0.60, 1.35) for HFO compared with CON], hazard rates <273 days of gestation [HRR: 1.00 (95% CI: 0.86, 1.18) and 0.91 (95% CI: 0.77, 1.07), respectively], and mean gestation durations [differences: 0.2 d (95% CI: -0.5, 0.8) and 0.6 d (95% CI: -0.06, 1.2), respectively]. Inspection of pregnancy survival curves suggested that LC n-3 PUFAs delayed delivery in low fish consumers by 5-10 d and that this effect ceased rapidly after stopping taking the capsules. CONCLUSION: This trial could not substantiate that fish oil prevents preterm birth in Chinese women, possibly because statistical power was too low. This trial was registered at clinicaltrials.gov as NCT02770456.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31408173

RESUMO

CONTEXT: Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified. OBJECTIVE: To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from the early pregnancy. PARTICIPANTS: Danish pregnant women and their live-born children including 1,242,353 children from a Nationwide Register-Based Cohort (NRBC), 1997-2016; 8,803 children from the Danish National Birth Cohort (DNBC), 1997-2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011-2015. MAIN OUTCOME MEASURES: Birth defects diagnosed before two years of age. RESULTS: In the NRBC, altogether 2,718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% confidence interval (CI): 6.7-6.8%) in non-exposed children, and higher after exposure to Methimazole/Carbimazole (9.6% (95% CI: 8.2-11.2%)) and Propylthiouracil (8.3% (6.7-10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs. 12.6%, p=0.8) and the NDRPC (15.1 vs. 15.4%, p=0.8). CONCLUSIONS: Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy, and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.

5.
Cancer Epidemiol ; 62: 101575, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31369943

RESUMO

BACKGROUND: The etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers. METHODS: We examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973-2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis. RESULTS: Acute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67-1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34-0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03-2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02-2.32; paternal: OR: 1.82, 95% CI: 1.05-3.17). CONCLUSION: Our results support the notion of a role of infections for some cancer types.

6.
Fertil Steril ; 112(3): 552-561.e2, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31311623

RESUMO

OBJECTIVE: To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): Overall, 15,800 children (70%) born during 2000-2003 into the Danish National Birth Cohort were categorized according to maternal use of combined oral contraceptive pills or progestin-only pills reported around gestational week 17: no exposure (reference), exposure 4 months before conception, and exposure in early pregnancy. Children self-assessed pubertal status using Web-based questionnaires from 11 years and biannually throughout puberty. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted mean age differences (months) for attaining individual pubertal milestones and overall pubertal timing. Proportion mediated by prepubertal body mass index. RESULT(S): In boys, intrauterine exposure to oral contraceptives showed a tendency toward slightly earlier mean age for voice break (months, -3.8; 95% confidence interval [CI] -6.5, -1.0) and first ejaculation (months, -2.9; 95% CI -5.9, 0.1) and a mean difference of -1.4 months (95% CI -3.3, 0.4) for overall pubertal timing. Girls with intrauterine exposure tended to have slightly earlier age at menarche (months, -1.9; 95% CI -4.0, 0.3) and Tanner breast stages and had a mean difference of -0.9 months (95% CI -2.7, 1.0) for overall pubertal timing. Exposure before conception was not associated with pubertal timing. Prepubertal body mass index did not play a mediating role. CONCLUSION(S): This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.

7.
Pharmacoepidemiol Drug Saf ; 28(9): 1204-1210, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348585

RESUMO

PURPOSE: Nitrosatable drugs can react with nitrite in the stomach and form N-nitroso compounds. Exposure to nitrosatable drugs has been associated with congenital malformations and preterm birth, but use during pregnancy as a cause of fetal death is not well-known. We examined if prenatally nitrosatable drug use is associated with risk of stillbirth. METHODS: A nationwide cohort was conducted using 554 844 women with singleton and first recorded pregnancies regardless of previous pregnancy history from the Danish Medical Birth Register from 1996 to 2015. Exposure was recorded by use of the Danish National Prescription Register and defined as women who had redeemed a prescribed nitrosatable drug in the first 22 weeks of pregnancy. The reference group was women with no redeemed prescribed nitrosatable drug in this time period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for stillbirth. RESULTS: Among the 84 720 exposed women, 348 had a stillbirth compared with 1690 stillbirths among the 470 124 unexposed women. Women who used any prescribed nitrosatable drug were more likely to have a stillbirth compared with unexposed women (aHRs 1.24; 95% CI, 1.03-1.49). CONCLUSION: Nitrosatable drug use during the first 22 weeks of pregnancy might increase risk of stillbirth. The findings should be interpreted cautiously because of important unmeasured factors that might influence the observed association, including maternal vitamin C intake, dietary, and other sources of nitrate/nitrite intake.

8.
Pharmacoepidemiol Drug Saf ; 28(9): 1180-1193, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359557

RESUMO

PURPOSE: We estimated the association between maternal antidepressant (AD) use in early pregnancy and risk of congenital heart defects. METHODS: We applied a case-time-control design with the aim of controlling for confounding from time-invariant factors and compared the results of the design to results from a cohort design in a population of 792 685 singletons born alive in Denmark during 1995-2008. In the case-time-control design, we identified children diagnosed with a congenital heart defect in the first 5 years of life (cases) and compared maternal AD use in the risk period (the first 3 months of pregnancy) and the reference period (gestational months 5-7). A nondiseased control group was included to adjust for time trends of exposure. In the cohort design, we identified children whose mothers redeemed at least one AD prescription in the first 3 months of pregnancy (the exposed) and two other groups including the unexposed children with maternal AD prescriptions in the 12 months before pregnancy. We applied conditional logistic regression and logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The case-time-control OR for any congenital heart defect was 1.03 (95% CI, 0.61-1.73), which was similar to the OR (1.09, 95% CI, 0.88-1.35) from the cohort design when we compared the exposed children with the unexposed children with maternal AD use before pregnancy. CONCLUSIONS: The case-time-control design provided results similar to the cohort design when the cohort design had a better confounder control strategy. We discussed the strengths and drawbacks of case-time-control design.

9.
PLoS Med ; 16(6): e1002831, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31199800

RESUMO

BACKGROUND: Socioeconomic disparities in infant mortality have persisted for decades in high-income countries and may have become stronger in some populations. Therefore, new understandings of the mechanisms that underlie socioeconomic differences in infant deaths are essential for creating and implementing health initiatives to reduce these deaths. We aimed to explore whether and the extent to which preterm birth (PTB) and small for gestational age (SGA) at birth mediate the association between maternal education and infant mortality. METHODS AND FINDINGS: We developed a population-based cohort study to include all 1,994,618 live singletons born in Denmark in 1981-2015. Infants were followed from birth until death, emigration, or the day before the first birthday, whichever came first. Maternal education at childbirth was categorized as low, medium, or high. An inverse probability weighting of marginal structural models was used to estimate the controlled direct effect (CDE) of maternal education on offspring infant mortality, further split into neonatal (0-27 days) and postneonatal (28-364 days) deaths, and portion eliminated (PE) by eliminating mediation by PTB and SGA. The proportion eliminated by eliminating mediation by PTB and SGA was reported if the mortality rate ratios (MRRs) of CDE and PE were in the same direction. The MRRs between maternal education and infant mortality were 1.63 (95% CI 1.48-1.80, P < 0.001) and 1.19 (95% CI 1.08-1.31, P < 0.001) for low and medium versus high education, respectively. The estimated proportions of these total associations eliminated by reducing PTB and SGA together were 55% (MRRPE = 1.27, 95% CI 1.15-1.40, P < 0.001) for low and 60% (MRRPE = 1.11, 95% CI 1.01-1.22, P = 0.037) for medium versus high education. The proportions eliminated by eliminating PTB and SGA separately were, respectively, 46% and 11% for low education (versus high education) and 48% and 13% for medium education (versus high education). PTB and SGA together contributed more to the association of maternal educational disparities with neonatal mortality (proportion eliminated: 75%-81%) than with postneonatal mortality (proportion eliminated: 21%-23%). Limitations of the study include the untestable assumption of no unmeasured confounders for the causal mediation analysis, and the limited generalizability of the findings to other countries with varying disparities in access and quality of perinatal healthcare. CONCLUSIONS: PTB and SGA may play substantial roles in the relationship between low maternal education and infant mortality, especially for neonatal mortality. The mediating role of PTB appeared to be much stronger than that of SGA. Public health strategies aimed at reducing neonatal mortality in high-income countries may need to address socially related prenatal risk factors of PTB and impaired fetal growth. The substantial association of maternal education with postneonatal mortality not accounted for by PTB or SGA could reflect unaddressed educational disparities in infant care or other factors.

10.
BMJ Open ; 9(5): e023134, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31152024

RESUMO

OBJECTIVES: Breast feeding is associated with health benefits for both mother and child, but many studies focusing on neurodevelopment have lacked information on important confounders and few randomised trials exist. Our objective was to examine the influence of breast feeding on child IQ at 5 years of age while taking maternal IQ and other relevant factors into account. DESIGN: Prospective observational study. SETTING: Population-based birth cohort in Denmark. PARTICIPANTS: We used data from The Lifestyle During Pregnancy Study 1782 mother-child pairs sampled from the Danish National Birth Cohort (n=101 042). OUTCOME MEASURES: Child IQ was assessed at age 5 years by the Wechsler Primary and Preschool Scales of Intelligence-Revised. On the same occasion maternal intelligence was assessed by Wechsler Adult Intelligence Scale and Raven's Standard Progressive Matrices. Exposure data on duration of breast feeding (n=1385) were extracted from telephone interviews conducted when the child was 6 and 18 months, and analyses were weighted by relevant sampling fractions. RESULTS: In multivariable linear regression analyses adjusted for potential confounders breast feeding was associated with child IQ at 5 years (categorical χ2 test for overall association p=0.03). Compared with children who were breast fed ≤1 month, children breast fed for 2-3, 4-6, 7-9 and 10 or more months had 3.06 (95% CI 0.39 to 5.72), 2.03 (95% CI -0.38 to 4.44), 3.53 (95% CI 1.18 to 5.87) and 3.28 (95% CI 0.88 to 5.67) points higher IQ after adjustment for core confounders, respectively. There was no dose-response relation and further analyses indicated that the main difference in IQ was between breast feeding ≤1 month versus >1 month. CONCLUSIONS: Breastfeeding duration of 1 month or shorter compared with longer periods was associated with approximately three points lower IQ, but there was no evidence of a dose-response relation in this prospective birth cohort, where we were able to adjust for some of the most critical confounders, including maternal intelligence.

11.
Int J Epidemiol ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237934

RESUMO

BACKGROUND: In many countries, an increased prevalence of obesity in pregnancy has coincided with a declining pubertal age. We aimed to explore the potential effect of maternal pre-pregnancy overweight and obesity on timing of puberty in sons and daughters. METHODS: Between 2012 and 2018, 15 819 of 22 439 invited children from the Danish National Birth Cohort, born 2000-03, provided half-yearly information from the age of 11 years on the pubertal milestones: Tanner stages, voice break, first ejaculation, menarche, acne and axillary hair. We estimated adjusted mean monthly differences (with 95% confidence intervals) in age at attaining the pubertal milestones for children exposed to maternal pre-pregnancy obesity [body mass index (BMI) ≥30.0 kg/m2] or overweight (BMI 25.0 to 29.9 kg/m2) with normal weight (BMI 18.5 to 24.9 kg/m2) as reference. In mediation analysis, we explored whether childhood BMI at age 7 years mediated the associations. RESULTS: Maternal pre-pregnancy obesity was associated with earlier age at attaining most pubertal milestones in sons, and pre-pregnancy overweight and obesity were associated with earlier age at attaining all pubertal milestones in daughters. When combining all pubertal milestones, pre-pregnancy obesity [sons: -1.5 (-2.5, -0.4) months; daughters: -3.2 (-4.2, -2.1) months] and overweight [daughters only: -2.6 (-3.3, -1.8) months] were associated with earlier timing of puberty. The associations in sons were completely mediated by higher childhood BMI and partly so in daughters. CONCLUSIONS: Maternal pre-pregnancy obesity appears to lower timing of puberty through childhood obesity in sons and mainly through other mechanisms in daughters.

12.
Obesity (Silver Spring) ; 27(8): 1314-1322, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199598

RESUMO

OBJECTIVE: Acetaminophen (paracetamol), a medication commonly used in pregnancy, has hormonal effects, as has been suggested in experimental studies. Developmental exposure to endocrine disruptors could predispose individuals to weight gain. This study evaluated the associations between prenatal acetaminophen exposure and overweight in childhood. METHODS: A total of 30,127 (age 7) and 24,934 (age 11) children in the Danish National Birth Cohort born during 1996 to 2002 were studied. Mothers reported acetaminophen use in telephone interviews conducted during pregnancy, and children's BMI and waist circumference were reported by parents at 7 and 11 years. Differences for BMI z score and waist circumference were estimated, as well as risk ratios for overweight in girls and boys adjusting for indications of use and other confounders. RESULTS: There were no consistent associations found for prenatal acetaminophen exposure and BMI z score or waist circumference in girls and boys at both ages. Prenatal acetaminophen exposure was associated with overweight in girls at age 11 (risk ratio 1.31, 95% CI: 1.10-1.56, if exposed in all three trimesters; P < 0.001 for cumulative weeks of exposure), but no association was found in boys. CONCLUSIONS: There was no strong association between prenatal acetaminophen exposure and childhood BMI, but the findings on frequent prenatal exposure to acetaminophen and overweight in girls warrant further investigation.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31114966

RESUMO

Associations between maternal depression and child behaviour problems may be biased due to depression-related distortions in the maternal reports. In this study, we compared the agreement between maternal, teacher and child ratings of hyperactivity/inattention (H/I), conduct (CD) and emotional (EM) problems measured with the Strengths and Difficulties Questionnaire in a population with depressed and non-depressed mothers. The sample of 12,961 11-year-old children was drawn from the Danish National Birth Cohort. We also examined the association between maternal depression before and during the child's life and child H/I, CD and EM problems when reported by the different informants. Agreement between the informants was assessed with the Bland-Altman limits of agreement (LOA) and associations were analyzed using multiple linear regression models. We found large discrepancies between maternal and teacher ratings of child behavioural problems measured with the SDQ and less discrepancy between maternal and child self-ratings. Better agreement between informants was found in the population of depressed mothers compared to non-depressed mothers for H/I and CD problems, and not for EM symptoms. The LOA for all three subscales were wide in both populations, with the largest intervals ranging from - 6 (Lower LOA) to 3 (Upper LOA) for H/I. Statistically significant associations were found between maternal depression, and child H/I and CD problems when reported by the mother but not the teacher and only by the child, when maternal depression had been present during the child's life. Our findings emphasize the importance of considering each informants' ratings when obtaining ratings from multiple sources.

14.
Int J Cancer ; 2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054169

RESUMO

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

15.
Occup Environ Med ; 76(8): 527-529, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31138675

RESUMO

OBJECTIVES: Only a small number of studies have reported on the association of parental occupational exposure to benzene and risk of childhood and adolescent leukaemias. We examined associations with acute lymphoblastic leukaemia (ALL) in this population-based study in Denmark. METHODS: Benzene was largely banned from Danish workplaces after 1975, thus this case-control study focused on the immediately prior years. Paediatric cancer cases (

16.
Asian J Androl ; 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950413

RESUMO

Pubertal development may be altered in boys with cryptorchidism and hypospadias, but existing knowledge is inconsistent. Therefore, we investigated the association between cryptorchidism and hypospadias and pubertal development in a large cohort study. Boys in the Puberty Cohort, a cohort nested within the Danish National Birth Cohort, were included in this study. Information on cryptorchidism and hypospadias was retrieved from the Danish National Patient Register. From 11 years until 18 years or full pubertal development, information on physical markers of pubertal development was provided biannually, including Tanner stages, axillary hair, acne, voice break, and first ejaculation. In multivariate regression models for interval censored data, the mean (95% confidence intervals [CIs]) differences in months in obtaining the pubertal markers between boys with and without the anomalies were estimated. Among 7698 boys, 196 (2.5%) had cryptorchidism and 60 (0.8%) had hypospadias. Boys with hypospadias experienced first ejaculation and voice break 7.7 (95% CI: 2.5-13.0) months and 4.5 (95% CI: 0.3-8.7) months later than boys without hypospadias. The age at attaining the Tanner stages for gonadal and pubic hair growth was also higher, though not statistically significant. Pubertal development seemed unaffected in boys with mild as well as severe cryptorchidism. In conclusion, hypospadias may be associated with delayed pubertal development, but pubertal development seems unaffected by cryptorchidism. The relation between hypospadias and later pubertal development may be due to the underlying shared in utero risk or genetic factors.

17.
Am J Epidemiol ; 188(7): 1270-1280, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30995291

RESUMO

Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996-2002), the Netherlands (2003-2004), Spain (2003-2008), and South Korea (2006-2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure-response relationships were found for shorter pregnancy duration (P < 0.001) and preterm birth (P = 0.003). We observed no association with fetal growth or birth weight. Maternal cell-phone use during pregnancy may be associated with shorter pregnancy duration and increased risk of preterm birth, but these results should be interpreted with caution, since they may reflect stress during pregnancy or other residual confounding rather than a direct effect of cell-phone exposure.

18.
Environ Health Perspect ; 127(1): 17004, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30628845

RESUMO

BACKGROUND: It remains unsettled whether prenatal exposure to perfluoroalkyl substances (PFASs) affects human reproductive health through potential endocrine disruption. OBJECTIVES: We aimed to explore the associations between prenatal exposure to several PFASs and various aspects of pubertal development in boys and girls. METHODS: We studied two samples ([Formula: see text] and 445) from the Puberty Cohort, nested within the Danish National Birth Cohort (DNBC), measuring PFAS in maternal plasma from early gestation. Data on pubertal development were collected biannually from the age of 11 y until full maturation, using web-based questionnaires. Outcomes were age at menarche, voice break, first ejaculation, and Tanner stages 2 to 5 for pubic hair, breast, genital development, and a combined puberty indicator. A regression model for censored data was used to estimate mean difference (months) in age at achieving the pubertal outcomes across tertiles of PFAS concentrations and with a doubling of PFAS concentrations (continuous). For perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), a meta-analysis was used to provide a weighted average of the point estimates from samples 1 and 2. RESULTS: Overall, prenatal exposure to PFOS, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PDFA) (girls) and PFHxS and PFHpS (boys) was associated with lower mean age at puberty marker onset. PFDA and PFNA exposure was associated with higher mean age at onset of puberty in boys. Nonmonotonic associations in girls (PFOS, PFHpS, PFDA) and boys (PFDA, PFNA) were observed, showing larger mean age differences for the combined puberty indicator in the middle tertile [girls: PFOS: [Formula: see text] mo, 95% confidence interval (CI): [Formula: see text], [Formula: see text]; PFHpS: [Formula: see text] mo, 95% CI: [Formula: see text], 1.85; PFDA: [Formula: see text] mo, 95% CI: [Formula: see text], 1.83; and boys: PFNA: 4.45 mo, 95% CI: [Formula: see text], 10.21; PFDA: 4.59 mo, 95% CI: [Formula: see text], 10.11] than in the highest tertile with the lowest as reference. CONCLUSIONS: Our population-based cohort study suggests sex-specific associations of altered pubertal development with prenatal exposure to PFASs. These findings are novel, and replication is needed. https://doi.org/10.1289/EHP3567.


Assuntos
Disruptores Endócrinos/efeitos adversos , Fluorcarbonetos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Puberdade/efeitos dos fármacos , Adolescente , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Feminino , Fluorcarbonetos/sangue , Humanos , Masculino , Gravidez/sangue
19.
Environ Health Perspect ; 127(1): 17006, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30676078

RESUMO

BACKGROUND: Higher concentrations of single perfluorinated alkyl acids (PFAAs) have been associated with lower birth weight (BW), but few studies have examined the combined effects of PFAA mixtures. PFAAs have been reported to induce estrogen receptor (ER) transactivity, and estrogens may influence human fetal growth. We hypothesize that mixtures of PFAAs may affect human fetal growth by disrupting the ER. OBJECTIVES: We aimed to study the associations between the combined xenoestrogenic activity of PFAAs in pregnant women's serum and offspring BW, length, and head circumference. METHODS: We extracted the actual mixture of PFAAs from the serum of 702 Danish pregnant women (gestational wk 11­13) enrolled in the Aarhus Birth Cohort (ABC) using solid phase extraction, high-performance liquid chromatography (HPLC), and weak anion exchange. PFAA-induced xenoestrogenic receptor transactivation (XER) was determined using the stable transfected MVLN cell line. Associations between XER and measures of fetal growth were estimated using multivariable linear regression with primary adjustment for maternal age, body mass index (BMI), educational level, smoking, and alcohol intake, and sensitivity analyses with additional adjustment for gestational age (GA) (linear and quadratic). RESULTS: On average, an interquartile range (IQR) increase in XER was associated with a [Formula: see text] [95% confidence interval (CI): [Formula: see text], [Formula: see text]] decrease in BW and a [Formula: see text] (95% CI: 0.1, 0.5) decrease in birth length. Upon additional adjustment for GA, the estimated mean differences were [Formula: see text] (95% CI: [Formula: see text], 4) and [Formula: see text] (95% CI: [Formula: see text], 0.0), respectively. CONCLUSION: Higher-serum PFAA-induced xenoestrogenic activities were associated with lower BW and length in offspring, suggesting that PFAA mixtures may affect fetal growth by disrupting ER function. https://doi.org/10.1289/EHP1884.


Assuntos
Disruptores Endócrinos/efeitos adversos , Desenvolvimento Fetal/efeitos dos fármacos , Fluorcarbonetos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Receptores Estrogênicos/metabolismo , Adulto , Peso ao Nascer/efeitos dos fármacos , Tamanho Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Fluorcarbonetos/sangue , Cabeça/crescimento & desenvolvimento , Humanos , Recém-Nascido , Masculino , Gravidez/sangue , Ativação Transcricional , Transfecção
20.
Eur J Epidemiol ; 34(6): 537-541, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30649703

RESUMO

Epidemiologists study associations but they are usually interested in causation that could lead to disease prevention. Experience show, however, that many of the associations we identify are not the causes we take an interest in (correlation is not causation). In order to proper translate association into causes, a set of causal criteria was developed 50-60 years ago and they became important tools guiding this translational process (sometimes correlation is causation). Best known of these are the Bradford Hill 'criteria'. In these last 50 years, epidemiologic theory and infrastructure have advanced rapidly without changes in these causal criteria. We think time has come to revisit the 'old' criteria to see which ones we should keep and which ones should be taken out or be replaced by new measures of association. Robustness of these criteria in attempts to make the association go away should have high priority. A group of renowned internationally recognized researchers should have this task. Since classifying associations as causes is often done in order to reduce or eliminate the exposures of concern results from conditional outcome research should also be used. We therefore suggest to add a 'consequence' criterion. We argue that a consequence criterion that provides a framework for assessing or prescribing action worthy or right in social contexts is needed. A consequence criterion will also influence how strict our causal criteria need to be before leading to action and will help in separating the 'causal discussion' and the discussion on what to do about it. A consequence criterion will be a tool in handling dilemmas over values (as social solidarity, fairness, autonomy). It will have implications for the interpretation and use of the procedural criteria of causality. Establishing interconnected procedural and consequence criteria should be a task for institutions representing and being recognized by experts, civil society and the state.


Assuntos
Causalidade , Métodos Epidemiológicos , Humanos
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