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Objectives We aimed to validate Web-based questionnaires for the common pregnancy complications gestational diabetes, gestational hypertension, and preeclampsia. Study Design and Setting We included 1,809 women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study who delivered in 2012–2017, for whom relevant data were complete. Sensitivity, specificity, and positive and negative predictive values of self-reported diagnoses of gestational diabetes, gestational hypertension, and preeclampsia were determined using obstetric records as reference standard. Furthermore, we assessed whether maternal characteristics affected disagreement between questionnaires and obstetric record. Results For gestational diabetes and preeclampsia, we observed very few false-positive and false-negative reports, yielding sensitivities of 93% (95% confidence interval [CI] 86–100) and 88% (95% CI 79–98), respectively, and specificities of 100%. Depending on the definition of gestational hypertension, sensitivity and positive predictive values ranged from 62% to 89% and 53% to 64%, respectively. Disagreement on gestational hypertension was associated with prepregnancy overweight and multiparity. Conclusion Self-reports of gestational diabetes and preeclampsia in Web-based questionnaires were valid, but the validity of gestational hypertension seemed to be lower because of relatively high numbers of false-positive reports. However, it is questionable whether an appropriate reference standard exists to validate this pregnancy complication.

Human genetics and genomics advances : HGG advances 3(2), 100093 (2022). doi:10.1016/j.xhgg.2022.100093, Published by Cell Press, Cambridge, Ma.

Background: Nitrous oxide (N2O) is a common inhalation anaesthetic used in medical, paramedical, and veterinary practice. Since the mid 1950's, concerns have been raised regarding occupational exposure to N2O, leading to many epidemiological and experimental animal studies. Previous evaluations resulted in the classification of N2O as a possible risk factor for adverse reproductive health outcomes based on animal data. Human data were deemed inadequate primarily because of simultaneous co-exposures to other risk factors for adverse reproductive and developmental outcomes, including other anaesthetic gases. Since previous evaluations, controversies regarding N2O use remained and new approaches for dose response modelling have been adopted, calling for an update and re-evaluation of the body of evidence. This review aims to assess available animal evidence on N2O reproductive and developmental outcomes to inform a health-based recommended occupational exposure limit (OEL) for N2O with a benchmark dose-response modelling (BMD) approach. Methods: Comprehensive searches in PubMed, EMBASE, and Web of Science were performed to retrieve all relevant studies addressing reproductive and developmental outcomes related to inhalation of N2O in animals. The articles retrieved were screened based on title-abstract and full text by two independent reviewers. After data extraction, an overview of all studies was created for the different endpoints, namely foetal outcomes (e.g. resorption), female outcomes (e.g. implantations), and male outcomes (e.g. sperm count). A subset of studies reporting on exposure relevant to workplace settings and with a sufficient number of tested doses were included in dose-response modelling using the BMD approach. Results: In total, 15.816 articles were retrieved, of which 47 articles were finally included while 4 of those were used for the quantitative data synthesis. The overall risk of bias was judged to be probably high (using OHAT risk of bias tool) and unclear (using SYRCLE's risk of bias tool). From eligible rat studies, three studies provided an acceptable result by fitting a Hill model to the dose-response data. The resulting benchmark dose lower bounds (BMDLs) from three studies converged to an average (±sd) exposure level of 925 ± 2 mg/m3 at an additional risk of one standard deviation of implantation losses above those observed in the control group (i.e. reduced number of live foetuses/mother). For extrapolation from rats to humans, an uncertainty factor of 10 was used and an additional factor of 5 was applied to account for interindividual variability within the population of workers. Conclusion: With this systematic review, all available evidence for reproductive toxicity and adverse developmental outcomes in animals resulting from inhalation exposure to N2O was used to derive a health-based OEL recommendation of 20 mg/m3 as 8-h time-weighted average., SCOPUS: re.j, info:eu-repo/semantics/published

Objectives The objective of this study was to validate a Web-based questionnaire completed by the mother to assess perinatal outcome used in a prospective cohort study. Study Design and Setting For 882 women with an estimated date of delivery between February 2012 and February 2015 who participated in the PRegnancy and Infant DEvelopment (PRIDE) Study, we compared data on pregnancy outcome, including mode of delivery, plurality, gestational age, birth weight and length, head circumference, birth defects, and infant sex, from Web-based questionnaires administered to the mothers 2 months after delivery with data from obstetric records. For continuous variables, we calculated intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs), whereas sensitivity and specificity were determined for categorical variables. Results We observed only very small differences between the two methods of data collection for gestational age (ICC, 0.91; 95% CI, 0.90–0.92), birth weight (ICC, 0.96; 95% CI, 0.95–0.96), birth length (ICC, 0.90; 95% CI, 0.87–0.92), and head circumference (ICC, 0.88; 95% CI, 0.80–0.93). Agreement between the Web-based questionnaire and obstetric records was high as well, with sensitivity ranging between 0.86 (termination of pregnancy) and 1.00 (four outcomes) and specificity between 0.96 (term birth) and 1.00 (nine outcomes). Conclusion Our study provides evidence that Web-based questionnaires could be considered as a valid complementary or alternative method of data collection.

Contains fulltext : 174098.pdf (Publisher’s version ) (Open Access) Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.

Background Hypertensive pregnancy disorders (HPD) such as preeclampsia (PE) or the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome are associated with an elevated cardiovascular disease (CVD) risk. Standardized prevention guidelines after pregnancy in these high-risk women are lacking. Hypertension is the first emerging risk factor after PE/HELLP pregnancies and is acknowledged as a major risk factor for CVD. Premature hypertension leads to various manifestations of end-organ damage at young age. Timely treatment of elevated blood pressure is mandatory, despite many of these women have long-term undetected and untreated hypertension before adequate treatment is initiated. Hypothesis The aim of our study is to assess whether home blood pressure monitoring (HBPM) in women with a previous pregnancy with PE/HELLP is a valuable tool for early detection of hypertension. Methods Women with a history of PE/HELLP syndrome (both early and late) aged 40–60 years are invited to participate. They are randomized between HPBM or ‘usual care’. Patients with a history of CVD, known hypertension and/or use of antihypertensive medication are excluded. The primary outcome is to evaluate feasibility and usability of HBPM after 1 year of follow-up. Secondary outcomes will be to assess the effectiveness of blood pressure (BP) home monitoring to detect hypertension, the efficacy of BP treatment, quality of life (QoL), health-related symptoms, work ability and life-style behaviour. Discussion The results of this study will provide information for optimal preventive strategies to detect hypertension in women after PE/HELLP.

PURPOSE Anorectal malformations (ARM) are major congenital malformations, which are assumed to have a multifactorial etiology with both genetic and environmental factors playing an important role. MATERIAL AND METHODS In a Dutch case-control study, we investigated the role of maternal and paternal risk factors in the etiology of ARM. Parents of 85 ARM cases and 650 controls filled in a questionnaire. Controls were children treated with ear ventilation tubes. The questionnaire contained questions about time to pregnancy (TTP), medical and family history, lifestyle factors, such as smoking, alcohol use, and vitamin intake, and occupation in the three months before and during pregnancy. RESULTS Forty percent of ARM cases had also urogenital tract malformations. A higher occurrence of fever during the first trimester of pregnancy was found for case mothers compared to control mothers, resulting in an OR of 7.8 (95% CI:1.2-48.6). Maternal occupational exposure to industrial cleaning agents and solvents increased the risk of ARM five times (OR:5.3, 95%CI:1.5-19.4). Overweight (BMI ≥ 25 kg/m2) before pregnancy also seemed to be associated with ARM (OR:1.9, 95%CI:1.1-3.3), as well as paternal occupational exposure to exhaust fumes (OR:2.0, 95%CI:1.0-4.0). Reported ARM in at least one first or second degree family member increased the risk of having a child with ARM more than thirty times (OR:33.9, 95%CI:2.9-398). CONCLUSIONS This is the first study investigating a wide range of risk factors in the etiology of ARM. Potential risk factors may be found in fever during pregnancy, maternal overweight, and occupational exposures, but a familial component seems likely as well.

PURPOSE Undescended Testes (UDT) is the most common birth defect in boys with a largely unknown etiology. The authors conducted a case-referent study on risk factors for UDT, focusing on maternal and paternal exposures to endocrine disruptors, in particular. MATERIAL AND METHODS Cases and referents were 203 boys with surgically corrected UDT and 629 boys with middle ear infection, who were recruited at 5 hospitals in the Eastern part of the Netherlands. Referents were frequency matched with the cases on regional postal codes to obtain similar geographical distributions. Both parents of cases and referents filled out postal questionnaires. Confounder adjusted odds ratios (OR) with 95 percent confidence intervals (CI) were estimated using unconditional logistic regression. RESULTS Corresponding with the literature, UDT was associated with low birth weight: OR 2.2 (95%CI 1.1-4.2), multiple gestation: OR 2.2 (95%CI 0.9-5.3), and familial occurrence of the disorder: OR 3.2 (95%CI 2.0-5.1). Use of oral contraceptives after conception also seemed to increase the risk of UDT: OR 3.6 (95%CI 1.0-12.5). Indications were found for associations with gestational preeclampsia, prescriptive drug use, and personal or occupational use of cosmetics immediately prior to or during the index pregnancy for both parents. Additionally, mothers of cases more often reported occupational exposure to dust of divers origins: OR 5.1 (1.6-16.4). CONCLUSIONS The findings reflect a number of risk factors for UDT in general, but provide only some support for a role of endocrine disruptors in its etiology. However, the associations with occupational exposures need a re-evaluation using more valid exposure assessment methods, which is currently being done.

Purpose Hypospadias shows familial clustering to some extent. The most consistent explanation for this is a multifactorial pattern of inheritance, implicating a combination of genes and environment. As anti-androgenic endocrine disruptors increase the risk of hypospadias, male hormones such as dihydrotesosterone (DHT) could be involved in the etiology of this malformation. DHT stimulates development of the genital tubercle in the external genitalia. The gene encoding 17-beta-hydroxysteroid-dehydrogenase (HSD17B3), which catalyzes the conversion of androstenedione to testosterone, and the gene encoding steroid-5-alpha-reductase type II (SRD5A2), which catalyzes the conversion of testosterone to DHT might be associated with hypospadias. The aim of this study was to investigate the association of one polymorphism in each of these genes with hypospadias. Material and methods A family-based design was used for this study. Blood or saliva was collected from 195 patients and both of their parents. The polymorphism in HSD17B3 (rs1810711) was genotyped using pyrosequencing and the polymorphism in SRD5A2 (rs523349, V89L) was analysed by Restriction Fragment Length Polymorphism Analysis. The Hardy-Weinberg equilibrium was tested to identify possible systematic errors in genotyping. The Transmission Disequilibrium Test was used to test the association of the variant allele with hypospadias. Only heterozygous parents are taken into account in this latter analysis. Results No deviation from Hardy-Weinberg equilibrium was observed for the polymorphisms in HSD17B3 and SRD5A2. For the polymorphism in HSD17B3, heterozygous parents transmitted the common allele 85 times and the variant allele 94 times. This difference was not statistically significant (p = 0.501). For the polymorphism in SRD5A2, the common allele was transmitted 91 times and the polymorphic allele 81 times (p = 0.446). Conclusions The two polymorphisms analysed in this study showed no association with hypospadias. Additional polymorphisms in these or other genes need to be genotyped before conclusions about involvement of the genes in hypospadias etiology can be drawn.