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Camilla Lomholt Kjersgaard,1 Linn Håkonsen Arendt,1,2 Andreas Ernst,1,3 Morten Søndergaard Lindhard,4,5 Jørn Olsen,1,6 Tine Brink Henriksen,5 Katrine Strandberg-Larsen,7 Cecilia Høst Ramlau-Hansen1 1Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; 2Department of Obstetrics and Gynecology, Horsens Regional Hospital, Horsens, Denmark; 3Department of Urology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Pediatrics, Randers Regional Hospital, Randers, Denmark; 5Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark; 6Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 7Department of Public Health, Section of Epidemiology, Copenhagen University, Copenhagen, DenmarkCorrespondence: Camilla Lomholt KjersgaardDepartment of Public Health, Research Unit for Epidemiology, Aarhus University, Bartholins Allé 2, Aarhus, 8000, DenmarkTel +45 40 19 44 38Email ck@ph.au.dkPurpose: Hypospadias is one of the most frequent male congenital malformations. It remains controversial whether maternal lifestyle during pregnancy may affects the risk of having a son with hypospadias, especially for smoking with many suggesting lower risk. We assessed the individual and joint associations between maternal cigarette smoking, pre-pregnancy body mass index (BMI), alcohol consumption, binge drinking, and caffeine consumption and occurrence of hypospadias in sons.Patients and Methods: This cohort study utilized the Danish National Birth Cohort and the Aarhus Birth Cohort, holding detailed information on lifestyle factors in early pregnancy between 1989 and 2012. The Danish health registers were used to identify boys with hypospadias, according to International Classification of Diseases. Potential confounders and covariates were identified by literature search and use of directed acyclic graphs. Missing data were handled by multiple imputation and Cox proportional hazards models were applied to analyse data.Results: In total, 85,923 live-born singleton boys were included in the study of whom 502 (0.6%) were diagnosed with hypospadias. Maternal smoking in early pregnancy was associated with lower occurrence of hypospadias. An increase of one cigarette smoked per day was associated with lower risk of having a son with hypospadias (adjusted hazard ratio (HR) 0.97 (95% confidence interval (CI) 0.94, 1.00)). However, sub-analyses suggested that the results may be prone to unadjusted confounding. We found no association between pre-pregnancy BMI, alcohol consumption, binge drinking, or caffeine consumption and hypospadias.Conclusion: Maternal smoking during pregnancy was associated with lower occurrence of hypospadias but we cannot exclude uncontrolled confounding. The other investigated maternal lifestyle factors were not associated with hypospadias in sons.Keywords: smoking, prenatal exposures, alcohol, caffeine, BMI, birth defects

Multisystem inflammatory syndrome in children (MIS-C) is a novel disease that is associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 Until now, only one study has attempted to estimate the incidence of MIS-C among SARS-CoV-2-infected children and adolescents.2 This study from the New York State has reported an incidence of MIS-C of 2 per 100,000 persons younger than 21 years of age between 1 March and 10 May 2020. In the same period and population, the incidence of laboratory-confirmed SARS-CoV-2 infection was 322 per 100,000, equivalent to an incidence of MIS-C of one in 161 of SARS-CoV-2-infected individuals.2 However, at this very early stage during the pandemic, access to SARS-CoV-2 PCR testing was very limited, particularly among asymptomatic children and adolescents. Thus, the estimated incidence from the New York State may have been overestimated. Based on seropositive individuals in Denmark, we aimed to estimate the incidence of MIS-C among SARS-CoV-2-infected children and adolescents during the first year of the pandemic.The study was a prospective nationwide cohort study of MIS-C using data from all 18 Danish paediatric departments, which serve 1,153,049 children and adolescents below 18 years of age. The study was carried out from 1 March 2020 to 28 February 2021. Each paediatric department had identified a principal investigator on 12 March 2020 as part of a nationwide paediatric COVID-19 research study. This study was approved by the Ethics Committee of Capital Region of Denmark (H-20028631) and the Danish Data Protection Agency (P-2019–29). Informed parental consent was provided before participation.We found that 23 patients had been diagnosed with MIS-C, based on the criteria devised by the World Health Organization and American Centers for Disease Control and Prevention. This equated to a yearly incidence of two per 100,000 individuals under 18. The patients had a median age of eight (range 2–17) years, nine patients were aged 12–17 and median hospitalisation was eight (3–24) days. We found that 13/23 (57%) had hypotension, five (22%) received vasopressor support, 12 (52%) were admitted to intensive care units. Twenty-one patients (91%) received intravenous immunoglobulin, 17 (74%) had steroids, and three (13%) were given anakinra while two cases were self-limiting. All the children survived. All cases had confirmed SARS-CoV-2 infection determined by either positive SARS-CoV-2 polymerase chain reaction prior to the diagnose of MIS-C (20 of 23 cases; 87%) (tested due exposure or symptoms) and/or positive SARS-CoV-2 serology (15 of 18 cases; 83%).The cumulative incidence of Danish children with SARS-CoV-2 was estimated from a nationwide seroprevalence surveillance study by the Statens Serum Institut of randomly selected individuals in March 2021.3 In this study, seroprevalence of SARS-CoV-2 in the Danish population was determined since August 2020 in the non-vaccinated population after personal invitation to persons above 12 years of age. These data were representative for all regions in Denmark with equal distribution. Detection of total antibodies to SARS-CoV-2 was determined by an enzyme-linked immunosorbent assay in serum (WANTAI Ab ELISA®). The study found that 43/530 (8.1%) individuals aged 12–17 years had positive SARS-CoV-2 immunoglobulin G in March 2021 (personal communication Laura Espenhain) and 7.0% (CI 6.6–7.4) of 10,631 adolescents and adults.3 This suggests an incidence of MIS-C of one in 3,700 in paediatrics patient aged above 12 years, based on nine MIS-C patients out of 33,183 positive for SARS-CoV-2. When we assumed the same seroprevalence for patients below 12 years of age, the overall incidence of MIS-C in children and adolescents was one in 4,100, based on 23 MIS-C patients out of 93,397 infected with SARS-CoV-2.This study provides an estimate of the risk of MIS-C after SARS-CoV-2 infection. MIS-C cases were determined by prospective nationwide data from all Danish paediatric departments, and we assume our case series was complete for several reasons. First, all cases underwent in-depth investigations for differential diagnoses. Second, all cases had either positive polymerase chain reaction (PCR) prior to MIS-C and/or positive SARS-CoV-2 serology. Third, children hospitalised with unexplained severe systemic inflammation in March and April 2020, before we became aware of MIS-C, were subsequently investigated with SARS-CoV-2 serology. However, as no unequivocal diagnostic criteria exist, milder self-limiting cases could have gone undiagnosed. In addition, hyperinflammatory conditions unrelated to SARS-CoV-2, but occurring in patients with previous SARS-CoV-2 infection, could have been diagnosed as MIS-C. Another limitation of this study was the relatively few MIS-C cases which probably was due to the relatively low SARS-CoV-2 infection rate in Denmark.With respect to Danish children and adolescents infected with SARS-CoV-2, we used nationwide seroprevalence data from children aged 12–17 years.3 These surveillance data included relatively few individuals encumbering the total number of SARS-CoV-2-infected children and adolescents with some uncertainty. The data were extrapolated to children below 12 years, as a previous nationwide Danish study in the same settings showed that the SARS-CoV-2 seroprevalence was equal across all childhood age groups.4 However, a Swiss population-based study found a lower seroprevalence in children below 10 years of age.5 Thus, the one in 4,100 risk of MIS-C may have been underestimated in younger children. On the contrary, the risk could also have been overestimated as antibodies may wane. A strength of our study was the serology-based estimate of the SARS-CoV-2 incidence, as this was more reliable than using PCR-positive cases. The calculated number of infected individuals, determined by serology (93,397), was more than twice the number of PCR-positive children (38,877), according to national PCR-surveillance data from 1 March 2020 to 28 February 2021. Hence, the incidence was calculated to be as high as one in 1,700 individuals, versus one in 4,100, if counting to PCR-positive children only. This reflected the fact that PCR test capacity was limited in Denmark during the first wave and the possibility that a significant proportion of children were not tested due to no, or just mild, symptoms. Accordingly, the previous estimate of the incidence of MIS-C among SARS-CoV-2-infected individuals from the New York State in spring 2020 was based on PCR-positive cases and found a 25-fold higher incidence than the incidence estimated in our study (one in 161 versus one in 4,100 in our population).2 Thus, it may also reflect that asymptomatic children and adolescents may not have undergone PCR testing in the New York State at this early stage of the pandemic.SARS-CoV-2 was initially regarded as a mild infection in children, but the emergence of MIS-C means that it is now recognised as an infection with a significant risk for serious complications.1 We have previously reported that the risk of hospital admission due to acute COVID-19 was one in 1,250 SARS-CoV-2-infected children and that they were hospitalised for a median of only two days, without intensive care.6 In contrast, the children with MIS-C in this study were hospitalised for a median of eight days and more than half required intensive care.In conclusion, despite this population-based prospective study is encumbered with several uncertainties, it confirms that MIS-C is a rare but serious complication of SARS-CoV-2 infection, which occurred in one in 4,100 infected children.

BackgroundA growing body of evidence supports the existence of an association between patient safety culture (PSC) and patient outcomes. PSC refers to shared perceptions and attitudes towards norms, policies and procedures related to patient safety. Existing literature shows that PSC varies among health professionals depending on their specific profession and specialty. However, these studies did not investigate whether PSC can be improved. This study investigates whether length of education is associated with improvements in PCS following a simulation intervention.MethodsFrom April 2017 to November 2018, a cross-sectional intervention study was conducted at two regional hospitals in Denmark. Two groups with altogether 1230 health professionals were invited to participate. One group included nurses, midwives and radiographers; the other group included doctors. A train-the-trainer intervention approach was applied consisting of a 4-day simulation instructor course that emphasised team training, communication and leadership. Fifty-three healthcare professionals were trained as instructors. After the course, instructors performed in situ simulation in their own hospital environment.OutcomesThe Safety Attitude Questionnaire (SAQ), which has 6 dimensions and 32 items, was used to collect main outcome variables. All employees from both groups were surveyed before the intervention and again four and nine months after the intervention.ResultsMean baseline scores were higher among doctors than among nurses, midwives and radiographers for all SAQ dimensions. At the second follow-up, four of six dimensions improved significantly (p ≤ 0.05) among nurses, midwives and radiographers, whereas no dimensions improved significantly among doctors.ConclusionOver time, nurses, midwives and radiographers improved more in PSC attitudes than doctors did.

The purpose was to examine the association between exercise during pregnancy and intelligence score in offspring. We analyzed data from 4008 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, recruited during pregnancy from July 1989 to November 1991 and their sons who were registered at conscription at 17-20 years of age. The women gave information by self-administered questionnaires during the first trimester including leisure-time physical activity and weekly hours of sport. This information was linked to the sons’ measures of intelligence by Børge Priens test scores from the Danish Conscription Registry. Only sons were included since very few women register at conscription in Denmark. The main outcome measure was the Børge Priens test score as a continuous variable and with a low score defined as

Linn Håkonsen Arendt,1– 3 Lars Henning Pedersen,1,4 Lars Pedersen,5 Per Glud Ovesen,1,6 Tine Brink Henriksen,7 Morten Søndergaard Lindhard,8 Jørn Olsen,2,5 Henrik Toft Sørensen,5 Cecilia Høst Ramlau-Hansen2 1Department of Obstetrics and Gynecology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of Public Health, Research Unit for Epidemiology, Aarhus University, Aarhus, Denmark; 3Department of Obstetrics and Gynecology, Regional Hospital Horsens, Horsens, Denmark; 4Department of Biomedicine, Aarhus University, Aarhus, Denmark; 5Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 6Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; 7Department of Child and Adolescent Health, Aarhus University Hospital, Aarhus, Denmark; 8Department of Child and Adolescent Health, Regional Hospital Randers, Aarhus, DenmarkCorrespondence: Linn Håkonsen ArendtDepartment of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark; Department of Public Health, Research Unit for Epidemiology, Aarhus, DenmarkTel +45 27 21 09 81Email lha@clin.au.dkPurpose: To study the occurrence of major congenital abnormalities in children of women with type 1 and type 2 diabetes and investigate the association between glycated haemoglobin (HbA1c) and major congenital malformations according to type 1 diabetes and type 2 diabetes separately.Patients and methods: In this register-based study, all singletons born alive from January 1, 2000 to December 31, 2015 in the North Denmark and Central Denmark regions of Denmark and their mothers were included. We used data from Danish health registers and the LABKA database. Logistic regression models were used to compute crude and adjusted prevalence odds ratios (cORs and aORs) with 95% confidence intervals (CIs) for major congenital malformations overall and for subtypes, by type of maternal pre-existing diabetes and HbA1c levels.Results: Among 314,245 infants included, 2020 (0.64%) had mothers with type 1 diabetes and 498 (0.16%) had mothers with type 2 diabetes. We found an aOR of 2.9 (95% CI: 2.5, 3.5) and 1.9 (95% CI: 1.3; 2.8) for major malformations for type 1 and type 2 diabetes, respectively. The highest occurrence was seen for major congenital heart diseases, but we also observed higher occurrence of several other non-cardiac malformations. For both type 1 and type 2 diabetes, the prevalence of major congenital malformations increased with higher levels of maternal HbA1c with no safe threshold level. Mothers with type 1 diabetes had higher risks than those without diabetes irrespective of HbA1c, and women with HbA1c levels ≥ 9.5% had 8 times the odds of major congenital malformations [aOR 8.7 (95% CI: 5.4; 14.5)].Conclusions: The prevalence of major congenital malformations progressively increased with poorer glycemic control during pregnancy, with no obvious safe threshold level, for both type 1 and type 2 diabetes.Keywords: congenital heart diseases, diabetes, epidemiology, malformations, pregnancy, register-based research

BackgroundA number of neonatal simulation-training programmes have been deployed during the last decade, and a growing number of studies have investigated effects of simulation-based team training. However, the body of evidence remains to be compiled. Therefore, we performed a systematic review on the effects of simulation-based team training on clinical performance and patient outcome.MethodsThe review was conducted according to the preferred reporting items for systematic review and meta-analysis (PRISMA). We included studies on team training in emergency neonatal settings with reported outcome on clinical performance and patient outcome. Two reviewers independently selected articles and assessed risk-of-bias using the Cochrane risk-of-bias tool 2.0 and the Newcastle-Ottawa quality assessment scale. Kirkpatricks’ model for evaluation of training programs provided the framework for a narrative synthesis.ResultsWe screened 1,434 titles and abstracts, evaluated 173 full-texts for eligibility, and included 24 studies. We identified only two studies with neonatal mortality outcome, and they had significant methodological limitations, and no conclusion could be reached regarding effects of simulation training in developed countries. Considering clinical performance, randomized studies showed improved team performance in simulated re-evaluations 3 and 6 months after the intervention.ConclusionsSimulation-based team training in neonatal resuscitation improves team performance and technical performance in simulation-based evaluations 3 to 6 months later. The current evidence was insufficient to conclude on neonatal mortality after simulation-based team training, since no studies were available from developed countries. Future research should include patient outcomes or clinical proxies of treatment quality whenever possible.

BACKGROUND: Although congenital abnormalities in the male reproductive tract are common, their causes remain poorly understood. We studied associations between hypertensive disorders of pregnancy (pre-gestational hypertension, gestational hypertension, and preeclampsia) and the genital anomalies, cryptorchidism (undescended testes), and hypospadias (ventrally displaced urethral meatus).METHODS: We established a population of 1,073,026 Danish boys born alive between 1 January 1978 and 31 December 2012. By means of Cox regression analyses, we estimated hazard ratios with 95% confidence intervals for cryptorchidism and hypospadias according to type and severity of hypertensive disorder. Further, we used restricted cubic spline analyses to investigate the association between gestational age at onset of severe and moderate preeclampsia and the two genital anomalies.RESULTS: We found associations between pre-gestational hypertension and cryptorchidism [HR: 1.3 (95% CI: 1.1, 1.6)] and hypospadias [HR: 1.7 (95% CI: 1.3, 2.3)], whereas gestational hypertension was only associated with cryptorchidism [HR: 1.2 (95% CI: 1.1, 1.4)]. Boys of mothers with preeclampsia had the highest occurrence of cryptorchidism and hypospadias, increasing with preeclampsia severity. Women with HELLP syndrome faced the highest risk of having a child with both cryptorchidism [HR: 2.1 (95% CI: 1.4, 3.2)] and hypospadias [HR: 3.9 (95% CI: 2.5, 6.1)]. Further, the occurrence increased with early onset of preeclampsia diagnosis.CONCLUSIONS: These findings support the hypotheses that preeclampsia and genital anomalies share common etiologic factors and that placental dysfunction and androgen deficiency in early pregnancy are important in the etiology of male genital anomalies.

Camilla Kjersgaard,1 Linn Håkonsen Arendt,1,2 Andreas Ernst,1 Morten Søndergaard Lindhard,2 Jørn Olsen,1,3 Tine Brink Henriksen,2 Katrine Strandberg-Larsen,4 Cecilia Høst Ramlau-Hansen1 1Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, 2Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Aarhus, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 4Department of Public Health, Section of Social Medicine, Copenhagen University, Copenhagen, Denmark Purpose: Cryptorchidism is the most frequent congenital malformation in boys and is associated with low sperm count, infertility and testicular cancer. Unhealthy maternal lifestyle during pregnancy such as smoking, high prepregnancy body mass index (BMI) as well as alcohol and caffeine intake may constitute possible risk factors for cryptorchidism, but results from the few previous studies are conflicting. We aimed to explore the association between maternal lifestyle factors and occurrence of cryptorchidism in sons.Patients and methods: The Danish National Birth Cohort and the Aarhus Birth Cohort provided information on maternal lifestyle from early pregnancy. Data were linked to several Danish health registers, multiple imputation was used to handle missing data and Cox proportional hazards models were used to adjust for potential confounders.Results: In total, 85,923 boys were included, and of them, 2.2% were diagnosed with cryptorchidism. We observed the strongest associations between maternal tobacco smoking and prepregnancy BMI and cryptorchidism. Sons of women who smoked 10–14cigarettes/day had the highest hazard ratio (HR) for cryptorchidism (1.37; 95% CI: 1.06–1.76), and for maternal BMI ≥30kg/m2, the HR was 1.32 (95% CI: 1.06–1.65). Binge drinking was associated with an HR

The most consistently reported risk indicators for the male genital anomalies cryptorchidism and hypospadias are prematurity and low birth weight. Placental dysfunction has been hypothesized as a possible underlying cause, and an association between placental weight at birth and hypospadias has been indicated. In a population-based cohort of 388,422 Danish singleton boys born alive (1997–2008), we studied the association between placental weight and cryptorchidism and hypospadias. Missing data were handled with multiple imputation, and we estimated hazard ratios by means of Cox regression models. During follow-up, 1,713 boys were diagnosed with hypospadias and 6,878 with cryptorchidism (3,624 underwent corrective surgery). We observed an association between low placental weight and risk of both genital anomalies. Boys with a placental weight in the lowest decile (

BACKGROUND: Physical activity is one of the best documented activities with impacts on health in children and adults. Children born preterm show reduced physical and psychosocial function compared to children born at term. This may influence their level of physical activity. Reports on moderately preterm children's physical activities during childhood are limited. Thus, the aim of this study was to compare the leisure time physical activity at age 9-11 years of moderately preterm children with that of children born at term.METHODS: Data from 4941 mother-child pairs from the Aarhus Birth Cohort (1989-91) were used. The cohort gathered clinical information, including gestational age at delivery. Information about parental socio-demographic and lifestyle factors was obtained from questionnaires completed during the second trimester of pregnancy. Information about children's physical activities was reported in a 9- to 11-year follow-up questionnaire completed by parents detailing how many times per week their child participated in sports activities outside of school, hours spent per week playing outside, and hours per week engaged in sedentary activities. Data were analysed using multiple logistic regression with the lowest activity group as a reference group.RESULTS: A total of 158 children (3.2%) were born moderately preterm, i.e., between 32 and 36 completed weeks. Children born moderately preterm participated in sports activities as often as their peers born at term; they also participated in frequent sports activities (≥ 4 times per week) as often as their peers. There were no differences in hours per week spent playing outside or in sedentary activities between the two groups.CONCLUSIONS: Nine- to 11-year-old moderately preterm children participated in sports activities outside school to a similar extent as their peers and engaged in outdoor activities and sedentary activities for the same duration of time per week as their peers born at term.

OBJECTIVE: To study if parental subfertility is related to the occurrence of the male genital anomalies, cryptorchidism and hypospadias.DESIGN: Population-based cohort study.SETTING: Not applicable.PATIENT(S): A total of 80,220 singleton boys and their mothers from the Danish National Birth Cohort and the Aarhus Birth Cohort.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): The two congenital anomalies; cryptorchidism and hypospadias, registered within the Danish National Patient Register up until December 31, 2012.RESULT(S): By means of Cox regression analyses, we found no associations between waiting time-to-pregnancy (TTP) and cryptorchidism or hypospadias among those who conceived spontaneously. The highest hazard ratio for cryptorchidism was seen among boys of couples with a TTP>12 months who conceived after fertility treatment (adjusted hazard ratio [aHR] 1.19, 95% confidence interval 0.92-1.55). For hypospadias, we found that boys of couples with a TTP>12 months who conceived after fertility treatment, had a 71% higher risk of hypospadias (aHR 1.71, [95% confidence interval 1.24-3.36]) as compared with boys of couples with a TTPCONCLUSION(S): The findings from this study showed that boys of couples with TTP>12 months who conceived after fertility treatment, had a higher occurrence of hypospadias than boys conceived spontaneously of couples with a short TTP. Among those who conceived spontaneously, TTP was not associated with hypospadias or cryptorchidism. These findings indicate that fertility treatment or severity of subfertility is related to hypospadias.

Background Pre-existing diabetes has been associated with an increased risk of congenital malformations overall, but studies on genital anomalies in boys are conflicting and possible causal mechanisms are not well understood. Previous studies have mainly assessed pregestational and gestational diabetes in combination. Yet considering the vulnerable time windows for the genital anomalies, associations could well differ between types of diabetes and between the 2 genital anomalies and we therefore aimed to study this further. Methods A population-based cohort study of 2,416,246 singleton live-born boys from Denmark (1978-2012) and Sweden (1987-2012) was carried out using Danish and Swedish register-based data. Using Cox regression models, we estimated hazard ratios for hypospadias and cryptorchidism according to maternal diabetes. We considered type and severity of diabetes, as well as timing of diagnosis in relation to birth. Results Pregestational type 1 diabetes was associated with a higher risk of both genital anomalies. The highest risks were seen for boys of mothers with diabetic complications (hazard ratio for hypospadias = 2.33 [95% confidence interval, 1.48, 3.66] and hazard ratio for cryptorchidism = 1.92 [95% confidence interval, 1.39, 2.65]). Gestational diabetes was associated with slightly increased risks of both genital anomalies. Conclusions These results are consistent with the hypothesis that poor glycemic control may interfere with fetal genital development in the critical early period of organogenesis. Given the widespread and increasing occurrence of diabetes, these results are of public health importance.

BACKGROUND: Overweight and obese pregnant women face higher risk of several critical birth outcomes, including an overall increased risk of congenital abnormalities. Only few studies have focused on associations between maternal overweight and the genital anomalies in boys, cryptorchidism and hypospadias, and results are inconclusive.METHODS: We performed a population-based cohort study and assessed the associations between maternal body mass index (BMI) in early pregnancy and occurrence of cryptorchidism and hypospadias. All live-born singleton boys born in Sweden from 1992 to 2012 were included. From the Swedish Patient Register, information on cryptorchidism and hypospadias was available. Data were analysed using Cox proportional hazards regression adjusted for potential confounders. Mediation analyses were performed to estimate how much of the association between BMI and genital anomalies were mediated through obesity-related diseases.RESULTS: Of the 1 055 705 live-born singleton boys born from 1992 to 2012, 6807 (6.4 per 1000) were diagnosed with hypospadias and 16 469 (15.6 per 1000) were diagnosed with cryptorchidism, of which 9768 (9.3 per 1000) underwent corrective surgery for cryptorchidism. We observed dose-response associations between maternal BMI and hypospadias and cryptorchidism. Boys of mothers with BMI ≥40.0 kg/m(2) had the highest adjusted hazard ratios for hypospadias (HR 1.35, 95% confidence interval [CI] 1.04, 1.76) and cryptorchidism (HR 1.25, 95% CI 1.00, 1.58). A substantial proportion of the associations between BMI and the genital anomalies were mediated through preeclampsia.CONCLUSION: This large register-based study adds to the current literature and indicates that the occurrence of hypospadias and cryptorchidism increase with maternal overweight and obesity severity.

OBJECTIVE: To investigate the association between maternal endometriosis and occurrence of the genital anomalies cryptorchidism and hypospadias in sons.DESIGN: Population-based cohort study.SETTING: Not applicable.PATIENT(S): All live-born singleton boys born from 1978 to 2012.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): Cryptorchidism and hypospadias in boys based on information from the Danish National Patient Register.RESULT(S): The study included 1,073,026 live-born singleton boys. A total of 6,443 boys were sons of women diagnosed with endometriosis before pregnancy. Altogether, 27,342 boys were diagnosed with cryptorchidism, of whom 16,446 had corrective surgery. Hypospadias was diagnosed in 4,853 boys. As compared with unexposed boys, a tendency towards a slightly higher occurrence of cryptorchidism was observed among boys of women with endometriosis (adjusted hazard ratio [aHR] 1.18; 95% confidence interval [CI], 0.97, 1.44). When stratified by medically assisted reproduction (MAR) technologies, the association was slightly stronger among boys born to women with endometriosis who had conceived via MAR, yet it remained moderate and statistically insignificant (aHR 1.27; 95% CI, 0.97, 1.70). When women who conceived with MAR were excluded, the association between endometriosis and cryptorchidism disappeared. For hypospadias, we observed no association, either in the main analysis or the stratified analysis.CONCLUSION(S): The findings from this register-based study do not provide strong evidence for a higher occurrence of the studied genital anomalies among boys of women with endometriosis.

International audience; Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity. © 2017, Springer Science+Business Media B.V.

Objectives Previous studies have shown that chemicals used in plastics manufacture are correlated with adverse health effects in humans, including reproductive abnormalities. Despite this growing evidence, little attention has been given to the potential health impact of highly exposed pregnant women employed in the plastics industry. The aim of this study was to assess the risk of cryptorchidism and hypospadias among boys born to mothers employed in the plastics industry using nationwide registers to extract maternal occupation and the child malformations of cryptorchidism and hypospadias. Methods The cohort included 864 747 boys born to a mother in employment during her pregnancy in Denmark from 1980–2007. These boys were followed for cryptorchidism and hypospadias from 1980–2009 comparing risks among sons of mothers working in the plastics industry (n = 5060) with sons of mothers working in other occupations (n = 717 921), including healthcare assistants and kitchen workers as references. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using multiple logistic regression, adjusting for parental age, birth years, parity, and geographical region. Results Preliminary results show sons of women employed in the plastics industry were not at increased risk of cryptorchidism (107 cases; OR 1.15, 95% CI: 0.95–1.40) or hypospadias (28 cases; OR 0.82, 95% CI: 0.56–1.19) compared to boys of women in other occupations (18 338 cases) and (3099 cases), respectively. Conclusions This nationwide cohort study did not find an increased risk of cryptorchidism or hypospadias amongst sons of mothers working in the plastics industry.

OBJECTIVE: To investigate whether children with a history of infantile colic showed impaired motor development at age 7 years compared with unaffected peers.STUDY DESIGN: We studied 27 940 children from the Danish National Birth Cohort (1997-2002), including 1879 (6.8%) with a history of infantile colic. Infantile colic was defined according to the modified Wessel criteria as crying for more than 3 hours per day and more than 3 days per week. We compared the parental Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) scores in children with and without infantile colic after adjustment for intrauterine exposures, feeding type, parity, maternal age, socioeconomic status, Apgar score, gestational age, and birth weight.RESULTS: Children with a history of infantile colic had an elevated risk of scoring above the predefined cutoff limit of possible or suspected developmental coordination disorder (OR, 1.3; 95% CI, 1.0-1.7; P = .034). The mean total DCDQ'07 score was -0.4 point (95% CI, -0.8 to 0) lower in children with a history of infantile colic. Moreover, they were at higher risk for a low total score (OR for a 10-point decrease, 1.1; 95% CI, 1.0-1.1; P = .006) and a low general coordination score (OR, 1.3; 95% CI, 1.1-1.5, P = .000) in the DCDQ'07. All associations appeared to be stronger among boys, but no statistically significant effect measure modification between infantile colic and sex was found.CONCLUSION: We found no evidence of a strong association between infantile colic and developmental coordination disorder in this large Danish cohort.

CONTEXT: Several neonatal simulation-training programs have been deployed during the last decade, and in a growing number of studies, researchers have investigated the effects of simulation-based team training. This body of evidence remains to be compiled. OBJECTIVE: We performed a systematic review of the effects of simulation-based team training on clinical performance and patient outcome. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. STUDY SELECTION: Two authors included studies of team training in critical neonatal situations with reported outcomes on clinical performance and patient outcome. DATA EXTRACTION: Two authors extracted data using a predefined template and assessed risk of bias using the Cochrane risk-of-bias tool 2.0 and the Newcastle-Ottawa quality assessment scale. RESULTS: We screened 1434 titles and abstracts, evaluated 173 full texts for eligibility, and included 24 studies. We identified only 2 studies with neonatal mortality outcomes, and no conclusion could be reached regarding the effects of simulation training in developed countries. Considering clinical performance, randomized studies revealed improved team performance in simulated re-evaluations 3 to 6 months after the intervention. LIMITATIONS: Meta-analysis was impossible because of heterogenous interventions and outcomes. Kirkpatrick’s model for evaluating training programs provided the framework for a narrative synthesis. Most included studies had significant methodologic limitations. CONCLUSIONS: Simulation-based team training in neonatal resuscitation improves team performance and technical performance in simulation-based evaluations 3 to 6 months later. The current evidence was insufficient to conclude on neonatal mortality after simulation-based team training because no studies were available from developed countries. In future work, researchers should include patient outcomes or clinical proxies of treatment quality whenever possible.