STUDY QUESTION
Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?.
SUMMARY ANSWER
Our results suggest an association between in utero ...exposure to perfluorooctanoic acid (PFOA) and delay in age of menarche.
WHAT IS KNOWN ALREADY
Previous cross-sectional studies have reported possible effects of PFASs on female reproduction including reduced fecundity, delayed puberty and accelerated age at menopause. Only limited data exist from follow-up studies on long-term implications of prenatal exposure to PFASs.
STUDY DESIGN, SIZE, DURATION
In this study we used data from a Danish population-based cohort established in 1988–1989. Of 1212 eligible pregnant women, 965 participated. Follow-up was initiated in 2008 on the female offspring at ∼20 years of age. Three hundred and sixty seven (84%) daughters answered a questionnaire and 267 (61%) daughters furthermore attended clinical examinations which were conducted in 2008–2009.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The final study population consisted of 343 daughters of which 254 had attended the clinical examinations and 89 had answered the questionnaire only. Levels of PFASs in maternal serum from pregnancy week 30 were used as a measure of prenatal exposure and related to age of menarche, menstrual cycle length, levels of reproductive hormones and follicle number of the daughters. Data were divided into three groups according to tertiles of maternal concentrations of PFASs (low, medium, high).
MAIN RESULTS AND THE ROLE OF CHANCE
In adjusted regression analyses, daughters exposed to higher levels of PFOA in utero had a 5.3 (95% confidence interval: 1.3; 9.3) months later age of menarche compared with the reference group of lower PFOA. Crude (P = 0.05) and adjusted (P = 0.01) trend tests also indicated a relationship between higher prenatal PFOA exposure and delay of menarche.
LIMITATIONS, REASONS FOR CAUTION
We did not measure the exact amount of PFASs to which the daughters had been exposed prenatally. Instead we used PFAS concentrations in maternal serum as surrogates. However, PFASs are efficiently transferred to the fetus via placenta. Information on age of menarche was collected retrospectively but the time interval for recall in our study was relatively short (2–10 years). The remaining outcome measures depended on participation in clinical examination which reduced the number of observations leading to limited statistical power and risk of selection bias.
WIDER IMPLICATIONS OF THE FINDINGS
Since PFASs can be detected in humans all over the world, effects of prenatal exposure on female reproductive function later in life may have wide health implications.
STUDY FUNDING/COMPETING INTEREST(S)
The study was supported by the Danish Council for Independent Research (271-05-0296, 09-065631), the Danish Ministry of Interior and Health (0-302-02-18/5), the Danish Council for Strategic Research (09-067124 (Centre for Fetal Programming), 09-063072, 2101-06-0005), the Novo Nordisk Foundation, the Aarhus University Research Foundation, the Frimodt-Heineke Foundation, the Foundation of Maria Dorthea and Holger From, the Beckett-Foundation, the Research Grant of Organon and the Foundation of Lily Benthine Lund. There are no competing interests.
Trial registration number
Not applicable.
We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg ...of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.
Objective
To examine the association between maternal hyper‐ and hypothyroidism and the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in the child.
Design
...A population‐based cohort study.
Setting
Singletons liveborn in Denmark between 1991 and 2004.
Population
A total of 857 014 singletons alive and living in Denmark at the age of 3 years.
Methods
Information on the diagnosis and/or treatment of maternal thyroid disease and the neurodevelopmental disorders ADHD and ASD in the child was obtained from Danish nationwide registers. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence interval (95% CI) for risk of ADHD and ASD in children born to mothers with thyroid dysfunction, adjusting for potential confounding factors.
Main outcome measures
ADHD and ASD in the child.
Results
Altogether, 30 295 singletons (3.5%) were born to mothers with thyroid dysfunction. Maternal hyperthyroidism diagnosed and treated for the first time after the birth of the child increased the risk of ADHD in the child (adjusted HR 1.23; 95% CI 1.05–1.44), whereas hypothyroidism increased the risk of ASD (adjusted HR 1.34; 95% CI 1.14–1.59). No significant association was seen for maternal diagnosis and treatment prior to the birth of the child.
Conclusions
Children born to mothers diagnosed and treated for the first time for thyroid dysfunction after their birth may have been exposed to abnormal levels of maternal thyroid hormone already present during the pregnancy, and this untreated condition could increase the risk of specific neurodevelopmental disorders in the child.
A number of intervention strategies against Campylobacter-contaminated poultry focus on postslaughter reduction of the number of cells, emphasizing the need for rapid and reliable quantitative ...detection of only viable Campylobacter bacteria. We present a new and rapid quantitative approach to the enumeration of food-borne Campylobacter bacteria that combines real-time quantitative PCR (Q-PCR) with simple propidium monoazide (PMA) sample treatment. In less than 3 h, this method generates a signal from only viable and viable but nonculturable (VBNC) Campylobacter bacteria with an intact membrane. The method's performance was evaluated by assessing the contributions to variability by individual chicken carcass rinse matrices, species of Campylobacter, and differences in efficiency of DNA extraction with differing cell inputs. The method was compared with culture-based enumeration on 50 naturally infected chickens. The cell contents correlated with cycle threshold (CT) values (R² = 0.993), with a quantification range of 1 x 10² to 1 x 10⁷ CFU/ml. The correlation between the Campylobacter counts obtained by PMA-PCR and culture on naturally contaminated chickens was high (R² = 0.844). The amplification efficiency of the Q-PCR method was not affected by the chicken rinse matrix or by the species of CAMPYLOBACTER: No Q-PCR signals were obtained from artificially inoculated chicken rinse when PMA sample treatment was applied. In conclusion, this study presents a rapid tool for producing reliable quantitative data on viable Campylobacter bacteria in chicken carcass rinse. The proposed method does not detect DNA from dead Campylobacter bacteria but recognizes the infectious potential of the VBNC state and is thereby able to assess the effect of control strategies and provide trustworthy data for risk assessment.
Summary
This study identified the costs and health-related quality of life impacts of several post-fracture multidisciplinary care pathways specific to individual skeletal site (hip, distal forearm, ...vertebrae, humerus). These care pathways may assist healthcare providers in allocating resources for osteoporotic fractures in more effective and cost-efficient ways.
Introduction
This micro-costing study was undertaken to provide the estimated healthcare costs of several fracture site-specific health service use pathways associated with different trajectories of health-related quality of life (HRQoL) 12-months post-fracture.
Methods
The study included 4126 adults aged ≥ 50 years with a fragility fracture (1657 hip, 681 vertebrae, 1354 distal forearm, 434 humerus) from the International Costs & Utilities Related to Osteoporotic fractures Study (ICUROS). ICUROS participants were asked to recall the frequency and duration (where applicable) of their health and community care service use at 4- and 12-month follow-up visits. Patient-level costs were identified and aggregated to determine the average cost of healthcare use related to the fracture in each care pathway (presented in Australian 2021 dollars). Mean cost differences were calculated and analysed using a one-way analysis of variance (ANOVA) and post hoc Bonferroni correction to determine any statistically significant differences.
Results
The total direct cost of fractures was estimated at $89564, $38926, $18333, and $38461AUD per patient for hip, vertebral, wrist, and humeral participants, respectively. A Kruskal–Wallis test yielded a statistically significant difference in cost values between most care pathways (
p
< 0.001). Of the 20 care pathways, those associated with recovery of HRQoL had lower mean costs per patient across each fracture site.
Conclusions
This study identified the costs and HRQoL impacts of several multidisciplinary care pathways for individual fracture sites based on the health service utilization of an international cohort of older adults. These care pathways may assist healthcare providers in allocating resources for fragility fractures in more effective and cost-efficient ways.
Bullying has been understudied among preschool children, especially those from Chinese American families. Previous research has also neglected the dimensional effects of psychological control on ...child bullying development. This study examined two psychological control dimensions, love withdrawal and guilt induction, and their effects on children's bullying aggressive behavior using a longitudinal design. Participants were first-generation Chinese American mothers (N = 133; mean age Mage = 37.82) and their preschool children (Mage = 4.48). Chinese immigrant mothers reported their psychologically controlling parenting and teachers rated children's bullying aggressive behaviors in the school setting. Confirmatory factor analyses were conducted to establish the psychometric properties and cross-wave measurement equivalence of the study constructs. Cross-lagged structural equation modeling analysis indicated that maternal love withdrawal prospectively predicted more bullying aggressive behavior, whereas guilt induction predicted less bullying aggressive behavior in children 6 months later. These results held after controlling for the initial level of children's problem behaviors and demographic variables (child age, gender, and maternal education). For child effects, child bullying aggressive behavior predicted more maternal guilt induction over time but not love withdrawal. Our findings highlight the importance of construct specificity and cultural context in understanding associations between parenting and child development.
As part of the effort to create the new Greenland Ice Core Chronology 2005 (GICC05) a synchronized stratigraphical timescale for the Holocene parts of the DYE‐3, Greenland Ice Core Project (GRIP), ...and North Greenland Ice Core Project (NGRIP) ice cores is made by using volcanic reference horizons in electrical conductivity measurements to match the cores. The main annual layer counting is carried out on the most suited records only, exploiting that the three ice cores have been drilled at locations with different climatic conditions and differences in ice flow. However, supplemental counting on data from all cores has been performed between each set of reference horizons in order to verify the validity of the match. After the verification, the main dating is transferred to all records using the volcanic reference horizons as tie points. An assessment of the mean annual layer thickness in each core section confirms that the new synchronized dating is consistent for all three cores. The data used for the main annual layer counting of the past 7900 years are the DYE‐3, GRIP, and NGRIP stable isotope records. As the high accumulation rate at the DYE‐3 drill site makes the seasonal cycle in the DYE‐3 stable isotopes very resistant to firn diffusion, an effort has been made to extend the DYE‐3 Holocene record. The new synchronized dating relies heavily on this record of ∼75,000 stable isotope samples. The dating of the early Holocene consists of an already established part of GICC05 for GRIP and NGRIP which has now been transferred to the DYE‐3 core. GICC05 dates the Younger Dryas termination, as defined from deuterium excess, to 11,703 years before A. D. 2000 (b2k), 130 years earlier than the previous GRIP dating.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is predominantly caused by alterations of the methyl-CpG-binding protein 2 (MECP2) gene. Disease severity and the presence of ...comorbidities such as gastrointestinal distress vary widely across affected individuals. The gut microbiome has been implicated in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) as a regulator of disease severity and gastrointestinal comorbidities. Although the gut microbiome has been previously characterized in humans with RTT compared to healthy controls, the impact of MECP2 mutation on the composition of the gut microbiome in animal models where the host and diet can be experimentally controlled remains to be elucidated. By evaluating the microbial community across postnatal development as behavioral symptoms appear and progress, we have identified microbial taxa that are differentially abundant across developmental timepoints in a zinc-finger nuclease rat model of RTT compared to WT. We have additionally identified p105 as a key translational timepoint. Lastly, we have demonstrated that fecal SCFA levels are not altered in RTT rats compared to WT rats across development. Overall, these results represent an important step in translational RTT research.
Background
There is increasing interest in the possible link between maternal hypothyroidism in the perinatal period and childhood asthma risk. We explored this in this study while accounting for the ...timing of hypothyroidism diagnosis. Further, we evaluated whether the risk was moderated by thyroid hormone treatment during pregnancy.
Methods
We conducted a population‐based cohort study using Danish national registers. All live‐born singletons in Denmark from 1998 to 2007 were identified. Maternal hypothyroidism and asthma in the children were defined by data from the Patient Register and Prescription Registry. We estimated incidence rate ratios (IRRs) of asthma among children born to hypothyroid mothers versus children born to mothers with no recorded thyroid dysfunction using Poisson regression models.
Results
Of 595 669 children, 3524 children were born to mothers with hypothyroidism diagnosed before delivery and 4664 diagnosed after delivery. Overall, 48 990 children received treatment for asthma. The IRRs of asthma was 1.16 (95% confidence interval (CI): 1.03‐1.30) and 1.12 (95% CI: 1.02‐1.24) for children born to mothers with hypothyroidism diagnosed before and after delivery, compared to children born to mothers with no thyroid dysfunction. The highest risk was observed among children born to mothers with hypothyroidism diagnosed before delivery who did not receive thyroid hormone treatment during pregnancy (IRR=1.37, 95% CI: 1.04‐1.80).
Conclusion
Our findings suggest that maternal hypothyroidism, especially when it is untreated, increases childhood asthma risk. Early detection and appropriate treatment of hypothyroidism in pregnant women may be an area for possible prevention of childhood asthma.
BACKGROUND According to the Rotterdam 2003 criteria, an ovary is defined as polycystic if 12 or more follicles of 2–9 mm are present, when evaluating the ovary by ultrasonography on Days 3–5 of the ...menstrual cycle in women not using hormonal contraceptives. The aim of this population-based study was to estimate the prevalence of polycystic ovaries (PCO) in a representative sample of young Danish women according to the Rotterdam criteria. METHODS From a Danish pregnancy cohort established in 1988–1989, 267 (61%) young adult daughters agreed to participate in a clinical examination and 174 (40%) consented to vaginal ultrasound. Sufficient image quality in at least one ovary was obtained from 154 women. Both users and non-users of hormonal contraceptives were included and the examination was not restricted to a particular time of the menstrual cycle. RESULTS The median (range) age was 20.1 (19.5–21.0) years. The median follicle number per ovary was 14 (6–30) and 12 or more follicles were counted in 104 of the 154 women. Thus, the prevalence was estimated to 68% 95% confidence interval (CI): 60–74%. PCO were present in 80% (95% CI: 65–89%) of non-users (n = 44) of hormonal contraceptives. Of the 104 women with PCO, 41% (95% CI: 32–51%) could be defined as having polycystic ovary syndrome. CONCLUSIONS A very large proportion of the young women had PCO according to the Rotterdam 2003 criteria. As the number of follicles is higher at a younger age, we believe the Rotterdam criteria should be revised, particularly to avoid misdiagnosis in this age group.
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