Febrile seizures and childhood epilepsy and risk of internalizing and psychotic symptoms.

OBJECTIVE: To assess whether children with febrile seizures and/or epilepsy were at increased risk of experiencing internalizing symptoms or psychotic-like experiences at age 11 years. METHODS: This cohort study includes 44 819 children from the 11-year follow up of the Danish National Birth Cohort. Information on childhood seizures was retrieved from the Danish National Patient Registry, whereas child psychiatric symptoms were assessed in a web-based questionnaire using the Adolescent Psychotic-like Symptom Screener and the Strength and Difficulties Questionnaire. Adjusted odds ratios (aORs) with corresponding 95% confidence intervals (CIs) for the association between childhood seizures and internalizing symptoms (symptom score ≥8) and psychotic-like experiences (≥2 definite experiences) were obtained using logistic regression models. RESULTS: A total of 1620 children with febrile seizures (3.6%), and 311 children with epilepsy (0.7%) were identified. When adjusted for potential confounders, no association between febrile seizures and psychiatric symptoms was observed, and no association was observed between epilepsy and psychotic-like experiences. However, the OR for internalizing symptoms was 1.76 (95% CI: 1.20-2.58) in children with epilepsy compared to children without. This higher risk was evident mainly in boys (OR 2.30, 95% CI 1.37-3.85), children with ≥2 epilepsy-related hospital admissions (OR 2.79, 95% CI 1.81-4.32), and children whose age at first epilepsy-related hospital admission was 0-3 years (OR 2.47, 95% CI 1.45-4.19). SIGNIFICANCE: No association was found between febrile seizures and psychiatric symptoms or epilepsy and psychotic-like experiences at age 11. However, boys with epilepsy were at higher risk of experiencing internalizing symptoms.

School Well-Being and Academic Performance of Children With Juvenile Idiopathic Arthritis: A National Register-Based Study.

OBJECTIVE: We aimed to investigate how school well-being (SWB) and academic performance of children with juvenile idiopathic arthritis (JIA) compare to their peers on a national level using the Danish national registers. Further, we investigated the potential influence of socioeconomic status (SES). METHODS: A population-wide, register-based, cross-sectional study was performed. We compared the results of children with and without JIA in the Danish National Well-Being Questionnaire (DNWQ), the National Danish School Testing (NDST), and their ninth grade (aged approximately 16 yrs) final school marks in Danish and mathematics. The results were analyzed using adjusted ordinal logistic regression (SWB) and linear regression (tests and marks). RESULTS: In separate cohorts, we included a total of 505,340 children answering the DNWQ, 812,461 children with NDST results, and the ninth-grade final marks of 581,804 children. Of these children, 1042, 1541, and 1410, respectively, fulfilled the criteria of JIA. Children with JIA reported SWB comparable to their peers, except for the question "Do you perform well in school?" (odds ratio 0.89, 95% CI 0.81-0.99). In the NDST, the children with JIA in general did just as well as their peers. We found no differences in the ninth-grade final marks in either Danish or mathematics. Stratifying the analyses on SES showed no significant differences in the associations. CONCLUSION: Overall, children with JIA report SWB comparable to that of children without JIA and perform equally well in school as children without JIA.

Identification of women at high risk of postpartum psychiatric episodes: A population-based study quantifying relative and absolute risks following exposure to selected risk factors and genetic liability.

BACKGROUND: We quantified relative and absolute risks of postpartum psychiatric episodes (PPE) following risk factors: Young age, past personal or family history of psychiatric disorders, and genetic liability. METHODS: We conducted a register-based study using the iPSYCH2012 case-cohort sample. Exposures were personal history of psychiatric episodes prior to childbirth, being a young mother (giving birth before the age of 21.5 years), having a family history of psychiatric disorders, and a high (highest quartile) polygenic score (PGS) for major depression. PPE was defined within 12 months postpartum by prescription of psychotropic medication or in- and outpatient contact to a psychiatric facility. We included primiparous women born 1981-1999, giving birth before January 1st, 2016. We conducted Cox regression to calculate hazard ratios (HRs) of PPE, absolute risks were calculated using cumulative incidence functions. RESULTS: We included 8174 primiparous women, and the estimated baseline PPE risk was 6.9% (95% CI 6.0%-7.8%, number of PPE cases: 2169). For young mothers with a personal and family history of psychiatric disorders, the absolute risk of PPE was 21.6% (95% CI 15.9%-27.8%). Adding information on high genetic liability to depression, the risk increased to 29.2% (95% CI 21.3%-38.4%) for PPE. CONCLUSIONS: Information on prior personal and family psychiatric episodes as well as age may assist in estimating a personalized risk of PPE. Furthermore, additional information on genetic liability could add even further to this risk assessment.

Social well-being and problematic school absence among Danish adolescents: A nationwide cross-sectional study.

AIM: Adolescents' well-being and school absence are important factors for public health. The aim of this study was to examine the association between social well-being and problematic school absence among Danish adolescents in the ninth grade, as well as to examine potential sex differences, using a large cohort of adolescents. METHODS: In this cross-sectional study, information on social well-being was obtained from the yearly Danish National Well-being Questionnaire mandatory in compulsory school. Data on school absence was obtained from the Ministry of Children and Education. The study population comprised 203,570 adolescents in the school years 2014/2015 to 2019/2020. The association between social well-being and problematic school-absence was analysed using logistic regression. A stratified analysis was made to investigate potential sex differences. RESULTS: A total of 17,555 (9.16%) adolescents had problematic school absence, defined as >10% illegal absence and/or sickness absence in the ninth grade. Adolescents with low social well-being had higher odds for having problematic school absence compared with adolescents with high social well-being, adjusted odds ratio=2.22 (95% confidence interval 2.10-2.34). When stratifying for sex, the association was strongest for girls. The results remained after adjustment for parents' educational level and family structure. CONCLUSIONS: Associations between adolescents' social well-being and problematic school absence were found, where girls had the strongest association. These findings might provide knowledge about social well-being as an important factor for problematic school absence, while underlining the importance of early focus and prevention, which is of importance for both the adolescents and society.

Divorce or Separation Following Postpartum Psychiatric Episodes: A Population-Based Cohort Study.

Objective: Psychiatric disorders are an established risk factor for divorce or separation. Despite the fact that 10%-15% of new mothers experience postpartum psychiatric episodes (PPEs), no previous studies have investigated the effects of PPEs on the probability of divorce in these new families. Therefore, this study aimed to investigate and quantify the probability of subsequent divorce/separation among women with either mild/moderate or severe PPE compared to mothers without PPE.Methods: This cohort study based on the national Danish registers included all cohabitating, primiparous women without previous psychiatric history who gave birth from 1996 through 2014. At 6 months postpartum, each woman's PPE status was evaluated and categorized as follows: (1) mild/moderate PPE (prescription of psychotropic medication-Anatomical Therapeutic Chemical Classification codes N03-N07), (2) severe PPE (psychiatric inpatient or outpatient treatment-International Classification of Disease, 10th Edition codes F00-F99, excluding codes for organic mental disorders, substance abuse, and mental retardation), and (3) no PPE (reference group). Subsequently, the status of cohabitation was assessed a maximum of 5 times (every January 1).Results: A total of 266,771 new mothers were included; 4,442 had a first mild/moderate PPE and 1,141 had a first severe PPE within 6 months postpartum. Compared to mothers without PPE, women with mild/moderate PPE had a significantly higher probability of later divorce (adjusted hazard ratio [HR] = 1.23; 95% CI, 1.15-1.31); for women with severe PPE, the probability was even greater (adjusted HR = 1.64; 95% CI, 1.45-1.85).Conclusions: Women experiencing their first-ever PPE following childbirth have a higher probability of divorce in the years following their diagnosis than mothers without PPE. Further, this study showed a dose-response relationship between the severity of PPE and the probability of divorce.

Association of Rheumatoid Arthritis in Pregnancy With School Performance of Offspring: A Danish Nationwide Register-Based Study.

OBJECTIVE: To examine the overall cognitive development of children exposed to maternal rheumatoid arthritis (RA) in utero by comparing their school test scores to those of their peers. METHODS: Children born in Denmark during 1995-2008 and listed in the National School Test Register were included (n = 738,862). Children exposed to maternal RA were identified through linkage of national registers. In separate analyses, exposure was subdivided according to maternal serostatus. Preclinical maternal RA was included as a separate exposure. The Danish national school tests are mandatory standardized tests. Results from all reading tests (grades 2, 4, 6, and 8) and mathematics tests (grades 3 and 6) from 2010-2017 were included. Test scores were compared according to maternal RA exposure for each test separately using linear regressions. RESULTS: We identified 934 children exposed to maternal RA in utero. There were no differences in reading test scores between maternal RA exposed and unexposed children. RA exposed children scored poorer in both mathematics tests (adjusted differences of mean score -0.14 SD (95% confidence interval [95% CI] -0.23, -0.06) and -0.16 SD (95% CI -0.26, -0.07). There was no appreciable difference between children by maternal RA serostatus. Children exposed to preclinical RA (n = 589) showed the same pattern of performance as children exposed to RA. CONCLUSION: RA-exposed children scored slightly poorer in mathematics tests but performed as well as their unexposed peers in the reading tests. The results do not suggest that RA in pregnancy has a major impact on offspring school performance.

Maternal pre-pregnancy overweight and infertility in sons and daughters: A cohort study.

INTRODUCTION: Overweight and obesity in pregnancy is increasing worldwide and may harm the developing fetus, including its future reproductive health. We therefore studied the association between in utero exposure to maternal overweight and obesity and infertility in adulthood. No studies have previously assessed this association. MATERIAL AND METHODS: We performed a cohort study with 9232 adult sons and daughters whose mothers were enrolled in the Danish Healthy Habits for Two cohort during pregnancy in 1984-87. Participants were sons and daughters followed in the Danish In-Vitro-Fertilization-Register and Danish National Patient Register until February 2018 for diagnoses of infertility. RESULTS: In total, 1203 (13%) sons and daughters were born to mothers with a body mass index (BMI) >25 kg/m2 ; 871 (9.4%) of the participants were identified as being infertile during follow-up. Sons of overweight mothers had slightly increased odds of infertility compared with sons of mothers with normal body weight (BMI 18.5-24.9 kg/m2 , adjusted odds ratio 1.4, 95% confidence interval [CI] 1.0-1.9). Cubic spline analyses with continuous BMI levels showed increasing odds with higher levels of BMI; however, for BMI >29 kg/m2 the confidence intervals were too wide to draw conclusions. No association between maternal overweight and infertility was found among daughters (adjusted odds ratio 0.9, 95% CI 0.7-1.2)). CONCLUSIONS: Sons born to overweight mothers had higher odds of infertility compared with sons of normal weight mothers. No association between maternal overweight and infertility was observed in daughters. Prevention of overweight during pregnancy may be an important tool to preserve fecundity in future generations.

Systemic lupus erythematosus during pregnancy is not associated with school performance in offspring - A Danish population-based study.

INTRODUCTION: Systemic lupus erythematosus (SLE) in pregnancy is considered a risk factor for a range of adverse outcomes in the offspring. Studies have indicated increased risk of neurodevelopmental disorders such as autism spectrum disorders, dyslexia and ADHD. However, the overall long-term cognitive development of children born to women with SLE has scarcely been examined. In this study, we compare test scores from the Danish National School Tests of children born to women SLE with children of the background population. METHODS: We included all singleton children born in Denmark between 1995 and 2008, who were listed in the Danish National School Test Register (n=738,862). Children born to women with SLE were identified through linkage of national healthcare registers. We assessed the children's performance in the national school tests between 2nd and 8th grade, in reading and mathematics. Information on the mothers' redeemed prescriptions in pregnancy was included in stratified analyses. Differences of mean test scores were derived from linear regressions and compared according to maternal SLE status, and predefined categories of medication exposures. RESULTS: In total, 312 (0.04%) children were born to mothers with SLE. There were no differences in performance in neither reading nor mathematics tests between those born to mothers with SLE and children born to mothers without SLE. When stratifying on medication exposures among children whose mothers had SLE, there was a non-significant tendency towards poorer results among those exposed to hydroxychloroquine and/or immunosuppressants (n=31), compared to those not exposed to these medications. A similar tendency was not observed among children whose mothers received hydroxychloroquine for non-SLE reasons (n=1,235). CONCLUSION: This study indicates no major harmful effect on the child's neurocognitive development from exposure in utero to SLE, hydroxychloroquine and/or immunosuppressants, as measured by school performance.

Cardiovascular biomarkers in the evaluation of patent ductus arteriosus in very preterm neonates: A cohort study.

BACKGROUND: The evaluation of the patent ductus arteriosus (PDA) in the very premature neonate is a challenge. Echocardiography provides an interpretation of the hemodynamic condition. It is however, only a snapshot. Biomarkers may represent a physiological response to the hemodynamic alterations brought on by the PDA and may add to the identification of the clinical significant PDA. AIM: To investigate the association between mid regional proadrenomodulin (MR-proADM), N-terminal pro b-type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro endothelin-1 (CT-proET1) and copeptin and echocardiographic measures of PDA. STUDY DESIGN: Cohort study with echocardiography performed on day 3 and 6. Blood samples from day 3. SUBJECT: 139 consecutive neonates born at a gestational age <32 weeks. OUTCOME MEASURES: The main outcomes were presence of a PDA day 3 and 6, PDA diameter, left atrium to aorta ratio (LA:Ao-ratio), and descending aorta diastolic flow (DADF). RESULTS: Adjusted plasma levels of all investigated biomarkers, except CT-proET1, were found to be associated with both PDA diameter and LA:Ao-ratio, and also the presence of a large PDA. CT-proET1 and copeptin was found to be associated with abnormal DADF. Using pre-specified cut-off values NT-proBNP and MR-proANP day 3 seemed to be of value in identifying a large PDA day 3 and 6 in very preterm neonates. CONCLUSION: Among the investigated biomarkers NT-proBNP and MR-proANP performed best in relation to echocardiographic markers of PDA severity in very preterm neonates.

Maternal depression and primary healthcare use for children: a population-based cohort study in Denmark.

BACKGROUND: Depression is a common mental illness worldwide. The offspring of a mother with depression has higher risk of developing mental and physical illness. AIM: This study aimed to investigate the association between the timing of maternal depression and the use of primary health care for the offspring. DESIGN AND SETTING: A population-based birth cohort study in Danish primary care using Danish national registers. METHOD: All Danish children born between 1 January 2000 and 31 December 2013 (n = 869 140 children) were included in the study. The primary outcome was number and type of annual contacts with the GP. The secondary outcome was specific services used by the GP to assess inflammatory and infectious disease in the children. Exposure was maternal depression of four categories: non-depressed, recent, previous, and past depression. The association was expressed as adjusted incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: Maternal depression was associated with a higher use of primary health care for all three categories of depression. The strongest association was found for children of a mother with recent depression; they had 16% more contacts than children of a non-depressed mother (adjusted IRR = 1.16, 95% CI = 1.15 to 1.17), and 19-24% more positive infectious-related tests were found in this group. CONCLUSION: Exposure to maternal depression was associated with a significantly higher use of primary health care for the offspring for all exposure categories. These findings reveal that healthcare use is higher for the offspring exposed to maternal depression, even several years after expected remission. The higher ratio of positive tests indicates that exposed children are ill with infectious disease more often.

Unrecognised coeliac disease among men and women undergoing fertility treatment: A screening study.

BACKGROUND: Coeliac disease is an autoimmune disease triggered by dietary gluten and has been associated with several conditions influencing female and male reproduction. Due to unspecific symptoms, coeliac disease can be unrecognised for years. OBJECTIVE: To estimate the prevalence of unrecognised coeliac disease among couples referred to fertility treatment. METHODS: Cross-sectional screening for coeliac disease in men and women referred to fertility treatment using IgA tissue transglutaminase antibodies as a marker of coeliac disease and small-bowel biopsies to confirm the diagnosis. Participants answered a questionnaire on gluten intake, gastrointestinal symptoms and reproductive history. RESULTS: A total of 893 participants (51% women) were screened and eight were coeliac disease antibody positive. Small-bowel biopsies were obtained from seven antibody positive participants and unrecognised coeliac disease was confirmed in one woman and three men, corresponding to a prevalence of 0.45% (95% confidence interval 0.12-1.14). The total prevalence, combining already diagnosed and unrecognised CD cases, was 0.63% (95% confidence interval 0.29-1.12). CONCLUSION: The prevalence of unrecognised coeliac disease in a group of infertile patients was equivalent to that of the Danish general population and low compared with that observed in the majority of other screening studies of infertile patients. Surprisingly, it should be noted that more men than women had coeliac disease. This result does not support a need for routine screening among infertile patients.

Potential combined effects of maternal smoking and coffee intake on foetal death within the Danish National Birth Cohort.

Background: Several studies have linked coffee intake and smoking to foetal death, but a possible interaction between both exposures remains unknown. Methods: We studied, within the Danish National Birth Cohort, the potential interaction between smoking and coffee drinking while pregnant on the risk of foetal (early and late) death. The study included 90 086 pregnant women, with information about their smoking habit and coffee intake in early pregnancy, and several potential confounding factors. Interaction was studied by calculating both the hazard ratio (HR) in Cox's regression (linear and smoothed restricted cubic spline) and the interaction contrast ratio (ICR). Results: Women who neither smoked nor drank coffee were used as the reference group. Drinking more than 3 cups/d of coffee was associated with the highest risk of foetal death, spontaneous abortion and stillbirth for all smoking status (non-smoker, ≤10 or > 10 cigarettes/d). Among smokers, the combination with drinking <3 cups/d of coffee presented the lowest HRa for foetal death, spontaneous abortion and stillbirth. The ICRs were negative when considering smokers who had a coffee intake up to 3 cups/d, but they were positive for those who had a higher coffee intake, suggesting the effect of coffee intake may be non-linear. Conclusion: Our results suggest that the combined effect of smoking and coffee intake during pregnancy on the risk of foetal death is coffee-dose-dependent. A low coffee intake may reduce the risk of foetal death associated with smoking while a high coffee intake increases the risk.

Prevalence, incidence, and autoimmune comorbidities of celiac disease: a nation-wide, population-based study in Denmark from 1977 to 2016.

AIM: The aim of this study was to describe and identify potential trends with respect to prevalence, incidence, age, sex, and autoimmune comorbidity of celiac disease (CD). PATIENTS AND METHODS: A Danish nationwide cohort study of CD using data from The National Patient Register. Patients with a primary or secondary diagnosis code of CD during the period 1977 to 2016 were identified. Information on sex, date of birth, death, or immigration was obtained from the Danish Civil Registration System, and autoimmune comorbidities were identified in the Danish National Patient Register. The CD cohort was compared with the general Danish population using a control cohort and aggregated data obtained from Statistics Denmark. RESULTS: The CD cohort consisted of 11 802 (65% women) patients. The median age at diagnosis of CD varied between 30 years in 1980-1984 and 45 years in 1995-1999 and 27 years in 2015-2016. The prevalence of CD in 1986 and 2016 was 14 and 180 per 100 000 persons, respectively, with a female/male ratio changing from 1.3 to 2.0. Incidence rates (per 100 000 person-years) changed from 1.6 in 1980-1984 to 15.2 in 2015-2016, with the largest increase among females aged 0-9 years. In 2016, prevalence of autoimmune comorbidities was 16.4% among the CD patients compared with 5.3% in the general population. CONCLUSION: The prevalence of diagnosed CD has doubled every decade in Denmark from 1986 to 2016, and in the same period the female/male ratio has increased and the median age at diagnosis has decreased. The prevalence of autoimmune comorbidity in 2016 was three times higher among CD patients compared with the general Danish population.

Temporal trends of lipophilic persistent organic pollutants in serum from Danish nulliparous pregnant women 2011-2013.

The use of the lipophilic persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs) and several organochlorine pesticides (OCPs) has been prohibited for more than 30 years. In this study, we present the temporal trends of the lipophilic POP serum concentrations in Danish nulliparous pregnant women between 2011 and 2013. We randomly selected 197 pregnant women (gestational age 11-13) from the Aarhus Birth Cohort. The concentrations of the lipophilic POPs in the serum samples were analyzed using gas chromatography. The concentrations were corrected for total serum lipids. The statistical analysis was performed by regression analysis with adjustment for age, BMI, gestational age at blood draw, and smoking status. The serum concentrations of PCB 118, 138, 153, 156, 170, 180, 187, and hexachlorobenzen, trans-nonachlor, ß-hexachlorocyclohexane (ß-HCH), and p,p'-dichlorodiphenyldichloroethylene were lower in 2013 than in 2011. However, the oxychlordane concentration was lowest in 2011. The serum levels of most lipophilic POPs followed downward trends during the study period, which was expected, as these compounds has been banned for many years. The upward trend of oxychlordane was unexpected and presumably a chance finding.

Urinary Neutrophil Gelatinase-associated Lipocalin in the evaluation of Patent Ductus Arteriosus and AKI in Very Preterm Neonates: a cohort study.

BACKGROUND: A patent ductus arteriosus (PDA) is frequently found in very preterm neonates and is associated with increased risk of morbidity and mortality. A shunt across a PDA can result in an unfavorable distribution of the cardiac output and may in turn result in poor renal perfusion. Urinary Neutrophil Gelatinase-associated Lipocalin (U-NGAL) is a marker of renal ischemia and may add to the evaluation of PDA. Our primary aim was to investigate if U-NGAL is associated with PDA in very preterm neonates. Secondary, to investigate whether U-NGAL and PDA are associated with AKI and renal dysfunction evaluated by fractional excretion of sodium (FENa) and urine albumin in a cohort of very preterm neonates. METHODS: A cohort of 146 neonates born at a gestational age less than 32 weeks were consecutively examined with echocardiography for PDA and serum sodium, and urine albumin and sodium were measured on postnatal day 3 and U-NGAL and serum creatinine day 3 and 6. AKI was defined according to modified neonatal Acute Kidney Injury Network (AKIN) criteria. The association between U-NGAL and PDA was investigated. And secondly we investigated if PDA and U-NGAL was associated with AKI and renal dysfunction. RESULTS: U-NGAL was not associated with a PDA day 3 when adjusted for gestational age and gender. A PDA day 3 was not associated with AKI when adjusted for gestational age and gender; however, it was associated with urine albumin. U-NGAL was not associated with AKI, but was found to be associated with urine albumin and FENa. CONCLUSIONS: Based on our study U-NGAL is not considered useful as a diagnostic marker to identify very preterm neonates with a PDA causing hemodynamic changes resulting in early renal morbidity. The interpretation of NGAL in preterm neonates remains to be fully elucidated.

Maternal serum concentrations of perfluoroalkyl acids in five international birth cohorts.

BACKGROUND: Perfluoroalkyl acids (PFAAs) are persistent and bioaccumulating compounds, which are spread all over the globe. We aimed to compare the PFAA concentrations in serum from pregnant women in five birth cohorts from four countries (Denmark, China, Norway, and Greenland). METHODS: Serum samples were obtained from the following five birth cohorts including a total of 4718 pregnant women: the Danish National Birth Cohort (DNBC, years 1996-2002, Denmark), the Aarhus Birth Cohort (ABC, years 2008-2013, Denmark), the Shanghai Birth Cohort (SBC, years 2013-2015, China), the Northern Norway Mother-Child Contaminant Cohort (MISA, years 2007-2009, Norway), and the Greenlandic Birth Cohort (ACCEPT, years 2010-2013, Greenland). The samples were analyzed using liquid chromatography triple-quadrupole mass spectrometry. To ensure comparability, all samples except for the MISA samples were measured in the same laboratory. We adjusted the log-transformed PFAA concentrations for age and parity using analysis of covariance. RESULTS AND DISCUSSION: The geometric mean (GM) of the summed concentrations of the seven most abundant PFAAs (∑PFAA) was 35ng/mL in the DNBC, 25 ng/mL in the SBC, 18ng/mL in the ACCEPT, 12ng/mL in the MISA cohort, and 12ng/mL in the ABC. The DNBC concentration was highest presumably because these samples were taken in earlier years (i.e. 1996-2002) than the samples from the other cohorts (i.e. 2007-2015), and at a time when the production of PFAAs were at the highest. When excluding the DNBC samples, we found that the concentrations of all the perfluorinated sulfonic acids (PFSAs) and one of the four perfluorinated carboxylic acids (PFCAs) were highest in the Greenlandic women, whereas the other three PFCAs were highest in the Chinese women. CONCLUSION: The concentration and composition of serum PFAAs were similar for the Danish ABC women and the Norwegian MISA women but were otherwise different across the cohorts. The different exposure profiles might partly be related to differences in lifestyle and diet. As the concentrations and compositional patterns vary between the countries, we suggest that the health implications associated with high PFAA exposure might also differ between the countries.

Diagnosing gestational diabetes mellitus in the Danish National Birth Cohort.

INTRODUCTION: The Danish National Birth Cohort (DNBC) contains comprehensive information on diet, lifestyle, constitutional and other major characteristics of women during pregnancy. It provides a unique source for studies on health consequences of gestational diabetes mellitus. Our aim was to identify and validate the gestational diabetes mellitus cases in the cohort. MATERIAL AND METHODS: We extracted clinical information from hospital records for 1609 pregnancies included in the Danish National Birth Cohort with a diagnosis of diabetes during or before pregnancy registered in the Danish National Patient Register and/or from a Danish National Birth Cohort interview during pregnancy. We further validated the diagnosis of gestational diabetes mellitus in 2126 randomly selected pregnancies from the entire Danish National Birth Cohort. From the individual hospital records, an expert panel evaluated gestational diabetes mellitus status based on results from oral glucose tolerance tests, fasting blood glucose and Hb1c values, as well as diagnoses made by local obstetricians. RESULTS: The audit categorized 783 pregnancies as gestational diabetes mellitus, corresponding to 0.89% of the 87 792 pregnancies for which a pregnancy interview for self-reported diabetes in pregnancy was available. From the randomly selected group the combined information from register and interviews could correctly identify 96% (95% CI 80-99.9%) of all cases in the entire Danish National Birth Cohort population. Positive predictive value, however, was only 59% (56-61%). CONCLUSIONS: The combined use of data from register and interview provided a high sensitivity for gestational diabetes mellitus diagnosis. The low positive predictive value, however, suggests that systematic validation by hospital record review is essential not to underestimate the health consequences of gestational diabetes mellitus in future studies.

Smoking, physical exercise, BMI and late foetal death: a study within the Danish National Birth Cohort.

The aim of this paper was to estimate the effect of maternal and paternal smoking on foetal death (miscarriage and stillbirth) and to estimate potential interactions with physical exercise and pre-pregnancy body mass index. We selected 87,930 pregnancies from the population-based Danish National Birth Cohort. Information about lifestyle, occupational, medical and obstetric factors was obtained from a telephone interview and data on pregnancy outcomes came from the Danish population based registries. Cox regression was used to estimate the hazard ratios (adjusted for potential confounders) for predominantly late foetal death (miscarriage and stillbirth). An interaction contrast ratio was used to assess potential effect measure modification of smoking by physical exercise and body mass index. The adjusted hazard ratio of foetal death was 1.22 (95 % CI 1.02-1.46) for couples where both parents smoked compared to non-smoking parents (miscarriage: 1.18, 95 % CI 0.96-1.44; stillbirth: 1.32, 95 % CI 0.93-1.89). On the additive scale, we detected a small positive interaction for stillbirth between smoking and body mass index (overweight women). In conclusion, smoking during pregnancy was associated with a slightly higher hazard ratio for foetal death if both parents smoked. This study suggests that smoking may increase the negative effect of a high BMI on foetal death, but results were not statistically significant for the interaction between smoking and physical exercise.