Increasing age at first childbirth has been suggested to increase the risk for infertility. Our objective is to determine whether women above thirty years of age historically have been able to ...sustain fertility rates above replacement level.
A descriptive nationwide Danish study using birth registries from 1901-2014.
Information on women's age at childbirth was obtained by using records from primary, secondary and tertiary institutions.
Mothers to 8,024,969 live births.
Mothers were stratified according to age at childbirth to determine total and age specific fertility rates.
Total fertility rate (TFR) decreased from 4.1 to 1.8 children per woman and age specific fertility also decreased from 1901 to 2014. Women aged 30-34, 35-39 or 40-44 years in the first decade of the 20th century had higher fertility rates than the corresponding five year younger age groups (25-29, 30-34 and 35-39, respectively) have had for the last 65 years. On average, women gave birth to two children after the age of 30 and one or more child after 35 years of age in the beginning of the 1900s. Furthermore, women more than 40 years of age accounted for 10% of TFR in 1901 compared with 4% in 2014 despite usage of assisted reproduction.
This nationwide study shows that women above 30 years of age historically have been able to sustain fertility rates above replacement level. This implies that other factors besides age are strong determinants of fertility in women above 30 years of age.
Abstract
Background
Exposure to perfluoroalkyl substances (PFASs) has been associated with changes in body mass index and adiposity, but evidence is inconsistent as study design, population age, ...follow-up periods and exposure levels vary between studies. We investigated associations between PFAS exposure and body fat in a cross-sectional study of healthy boys.
Methods
In 109 boys (10–14 years old), magnetic resonance imaging and dual-energy X-ray absorptiometry were performed to evaluate abdominal, visceral fat, total body, android, gynoid, android/gynoid ratio, and total fat percentage standard deviation score. Serum was analysed for perfluorooctanoic acid, perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid, perfluorononanoic acid, and perfluorodecanoic acid using liquid chromatography and triple quadrupole mass spectrometry. Data were analysed by multivariate linear regression.
Results
Serum concentrations of PFASs were low. Generally, no clear associations between PFAS exposure and body fat measures were found; however, PFOS was negatively associated with abdominal fat (
β
= -0.18,
P
= 0.046), android fat (
β
= -0.34,
P
= 0.022), android/gynoid ratio (
β
= -0.21,
P
= 0.004), as well as total body fat (
β
= -0.21,
P
= 0.079) when adjusting for Tanner stage.
Conclusions
Overall, we found no consistent associations between PFAS exposure and body fat. This could be due to our cross-sectional study design. Furthermore, we assessed PFAS exposure in adolescence and not in utero
,
which is considered a more vulnerable time window of exposure.
Asthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting ...abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children.
We studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex.
Among the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23).
Our findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.
Studies in rodents indicate that phthalates can function as adjuvants, increasing the potency of allergens. Meanwhile, epidemiological studies have produced inconsistent findings regarding ...relationships between phthalate exposures and allergic disease in humans. The present study examined phthalate exposure and allergic sensitization in a large group of 3–5 year old children: 300 random controls and 200 cases with asthma, rhinoconjunctivitis or atopic dermatitis as reported in questionnaires. The children were clinically examined to confirm their health status. Blood samples were analyzed for IgE sensitization to 20 allergens. Adjusted logistic regressions were used to look for associations between phthalate exposure indicators (mass fractions in dust from children's homes and daycares, metabolites in urine, and estimated daily indoor intakes from dust ingestion, inhalation and dermal absorption) and sensitization and allergic disease. No direct associations were found between phthalate exposures and asthma, rhinoconjunctivitis or atopic dermatitis. However, among children with these diseases, there were significant associations between non-dietary exposures to DnBP, BBzP and DEHP in the indoor environment (mass fractions in dust or daily indoor intakes from dust ingestion, inhalation and dermal absorption) and allergic sensitization. Some exposure pathways were more strongly associated with sensitization than others, although the results are not conclusive and require confirmation. A number of the associations depended on accounting for a child's exposure in more than one environment (i.e., daycare facility as well as home). Significant associations were not observed between phthalate metabolites in urine, which reflected exposure from diet as well as indoor pathways, and allergic sensitization.
•Phthalate exposures in the indoor environment may play a role in IgE sensitization.•Phthalates' effect on sensitization was stronger in children with allergic disease.•No direct associations were found between phthalate exposures and allergic disease.•Some exposure pathways were more strongly associated with sensitization than others.•Associations depended on accounting for exposure in more than one environment.
Background: Animal studies indicate that some phthalate metabolites may harm female reproductive function. Objectives: We assessed the associations between exposure to phthalate metabolites and ...pregnancy loss. Methods: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, n = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother. Results: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% CI: 4.5,369.5). Conclusions: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.
► In 438 adolescent boys from the Faroe Islands, a higher polychlorinated biphenyl (PCB) concentration in cord blood was associated with lower serum concentrations of both luteinizing hormone (LH) ...and testosterone, and higher sex hormone binding globulin (SHBG) concentrations. ► The concurrent PCB exposure was also positively associated with the SHBG concentration. ► In a structural equation model, a doubling in prenatal PCB exposure was associated with a decrease in LH of 6% (p=0.03). ► These signs of delayed puberty may be ascribed to a central hypothalamo-pituitary mechanism.
Because polychlorinated biphenyls (PCBs) are thought to cause endocrine disruption, we examined 438 adolescent boys from a birth cohort in the Faroe Islands, where PCB exposures are elevated. We measured PCBs and p,p′-dichlorodiphenyldichloroethylene (DDE) in cord blood and in serum from clinical examination at age 14. Higher prenatal PCB exposure was associated with lower serum concentrations of both luteinizing hormone (LH) and testosterone. In addition, sex hormone binding globulin (SHBG) was positively associated with both prenatal and concurrent PCB exposures. The PCB–SHBG association was robust to covariate adjustment. In a structural equation model, a doubling in prenatal PCB exposure was associated with a decrease in LH of 6% (p=0.03). Prenatal exposure to PCB and DDE showed weak, non-significant inverse associations with testicular size and Tanner stage. DDE was highly correlated with PCB and showed slightly weaker associations with the hormone profile. These findings suggest that delayed puberty with low serum-LH concentrations associated with developmental exposure to non dioxin-like PCBs may be due to a central hypothalamo-pituitary mechanism.
Prenatal phthalate exposure has been suggested to alter immune responses and increase the risk of asthma, eczema and rhinitis. However, few studies have examined the effects in prospective cohorts ...and only one examined rhinitis. We therefore studied associations between maternal urinary concentrations of phthalate metabolites and asthma, eczema and rhinitis in offspring aged 5 years.
From 552 pregnant women in the Odense Child Cohort, we quantified urinary concentrations of 12 phthalate metabolites in third trimester. We assessed asthma, rhinitis and eczema in their offspring at age 5 years with a questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC), and conducted logistic regression adjusting for relevant confounders.
7.4% of the children had asthma, 11.7% eczema and 9.2% rhinitis. Phthalate exposure was low compared to previous cohorts. No significant associations between prenatal phthalate exposure and asthma were found. Odds ratios (ORs) of child rhinitis with a doubling in ΣDiNP
and di-2-ethylhexyl phthalate metabolite (ΣDEHP
) concentrations were, respectively, 1.15 (95% confidence interval (CI) 0.97,1.36) and 1.21 (CI 0.93,1.58). The OR of eczema when doubling ΣDiNP
was 1.24 (CI 1.00,1.55), whereas the OR of using medicine against eczema when doubling a di-ethyl phthalate (DEP) metabolite was 0.81 (CI 0.68,0.96).
The lack of association between maternal phthalate exposure and asthma in the offspring may be due to low exposure and difficulties in determining asthma in 5-year-olds. The higher odds of rhinitis may raise public concern but further research in larger cohorts of older children is warranted.
Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- ...and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs - Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) - were measured at three timepoints (maternal serum in pregnancy week 34-36 and child serum at ages 5 and 13 years) and their association with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR-unvaccinated children, higher levels of the five PFASs at age 5 years were associated with increased odds of asthma at ages 5 and 13. The associations were reversed among MMR-vaccinated children. Prenatal PFAS exposure was not associated with childhood asthma or allergic diseases regardless of MMR vaccination status. In conclusion, PFAS exposure at age 5 was associated with increased risk of asthma among a small subgroup of MMR-unvaccinated children but not among MMR-vaccinated children. While PFAS exposure may impact immune system functions, this study suggests that MMR vaccination might be a potential effect-modifier.
Abstract
Perfluoroalkyl substances (PFAS) are persistent chemicals capable of crossing the placenta and passing into breast milk. Evidence suggests that PFAS exposure may affect brain development. We ...investigated whether prenatal or early postnatal PFAS exposure was associated with intelligence quotient (IQ) scores in schoolchildren from the Odense Child Cohort (Denmark, 2010–2020). We assessed concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) in maternal serum collected during the first trimester of pregnancy and in child serum at age 18 months. At 7 years of age, children completed an abbreviated version of the Wechsler Intelligence Scale for Children, Fifth Edition, from which Full Scale Intelligence Quotient (FSIQ) and Verbal Comprehension Index scores were estimated. In multiple linear regression analyses conducted among 967 mother-child pairs, a doubling in maternal PFOS and PFNA concentrations was associated with a lower FSIQ score, while no significant associations were observed for PFOA, PFHxS, or PFDA. PFAS concentrations at age 18 months and duration of breastfeeding were strongly correlated, and even in structural equation models it was not possible to differentiate between the opposite effects of PFAS exposure and duration of breastfeeding on FSIQ. PFAS exposure is ubiquitous; therefore, an association with even a small reduction in IQ is of public health concern.
Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear.
To evaluate ...associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents.
We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects.
In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: −0.19, −0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: −0.14, −0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: −0.25, 0.03, per joint exposure quantile).
In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.
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