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Aim: This study aimed to estimate the relative representation of childhood psychiatric diagnoses and use of psychotropic medication in the Danish National Birth Cohort (DNBC) compared to the general population. Methods: The general population was identified as all childbirths in Denmark during 1998–2002 (N =344,160). Linking the DNBC (N =91,442) and the general population to the Danish national health registries, all children were followed until they received an ICD-10 psychiatric diagnosis, had a prescription of psychotropic medication or to the end of follow-up in 2013. The prevalence ratios (PRs) with corresponding 95% confidence intervals (CI) were estimated for each psychiatric diagnosis and by sex. Age at first diagnosis presented as means were compared using the one-sample t -test. Results: In the DNBC, the selected childhood psychiatric diagnoses were underrepresented by 3% (PR=0.97, 95% CI 0.94–0.99), ranging from a 20% underrepresentation for schizophrenia (PR=0.80, 95% CI 0.59–1.09) to a 6% over-representation for anxiety disorder or obsessive-compulsive disorder (PR=1.06, 95% CI 0.97–1.17). The majority of the specific diagnoses were modestly underrepresented in the DNBC compared to the general population, while use of psychotropic medication had similar representation. Girls were generally more underrepresented than boys. Depression was on average diagnosed 0.4 years earlier in the DNBC than in the general population (p =0.023). Conclusions: These findings suggest that the social selection may influence the prevalence of diagnosed childhood psychiatric disorders in the DNBC. [ABSTRACT FROM AUTHOR]

Background Conventional cohort studies have consistently shown that exposure to maternal smoking in pregnancy is associated with about twice the risk of attention deficit hyperactivity disorder (ADHD) in the offspring. However, recent studies using alternative designs to disentangle the effect of social and genetic confounders have suggested that confounding may account for the association. In this study we aimed to estimate the association by a sibling design. Methods We used a design with half and full siblings in a Danish national register-based cohort on all singletons born between January 1991 and December 2006 and followed until January 2011. Data were available for 90% ( N = 968,665) of the singleton live births in the period. We used the combination of the International Classification of Diseases (10th version) diagnosis of hyperkinetic disorder (HKD) and ADHD medication to identify children. We used sibling-matched (conditional) Cox regression to control social and genetic confounding. Results Using conventional cohort analyses, we found the expected association between pregnancy smoking and offspring ADHD (adjusted HR 2.01, 95% CI 1.94-2.07). In the sibling analysis, however, we did not detect such a strong association (adjusted HR 1.07, 95% CI 0.94-1.22). There was no difference between results for half- and full sibling analyses. The link between pregnancy smoking and low birth weight remained robust in the sibling design (adjusted OR 1.68, 95% CI 1.33-2.12). Conclusions We found no support for prenatal smoking as a strong causal factor in ADHD. Our findings suggest that the strong association found in most previous epidemiological studies is likely to be due to a strong link between maternal smoking and maternal ADHD genetics or shared family environment. Pregnant women should still be encouraged to stop smoking because of other risks, but we have no reason to believe that this would reduce the risk of ADHD in the offspring. [ABSTRACT FROM AUTHOR]

The article reports a study which examined whether the onset of rheumatoid arthritis (RA) in women before conception affects the time to pregnancy (TTP). It mentions that the study evaluated pregnant women who enrolled in the Danish National Birth Cohort between 1996 and 2002, and used the Danish National Hospital Discharge Registry to identify women with RA. Details pertaining to the methods, data analysis and study results are also presented.

Abstract: Background: Mixed-handedness, which may reflect atypical brain laterality, has been linked to a number of medical conditions as well as prenatal stress. Aims: The aim of the study was to examine whether infertility or infertility treatment was associated with an increased risk of mixed-handedness in children. Study design, subjects and outcome measures: We used data from three population-based birth cohorts in Denmark: the Aalborg-Odense Birth Cohort (1984–1987), the Aarhus Birth Cohort (1990–1992) and the Danish National Birth Cohort (1996–2002) (N =7728, 5720 and 29486, respectively). Data on time to pregnancy and infertility treatment were collected during pregnancy. Handedness was reported in a follow-up questionnaire when the children were at least 7years old. Children were categorized as mixed-handed if their mothers reported that they used both hands equally. Results: Children born after infertility treatment, particularly intrauterine insemination, had a higher risk of being mixed-handed compared to children of fertile couples with a time to pregnancy ≤12months (odds ratio 1.41, 95% confidence interval 1.09–1.82). Children of couples with unplanned pregnancies, particularly after an oral contraceptives failure, were also more likely to be mixed-handed. There was no association between a long waiting time to pregnancy and mixed-handedness in children. Conclusions: Children born after infertility treatment, particularly intrauterine insemination, and children exposed to oral contraceptives during early gestation may have a higher risk of being mixed-handed. [Copyright &y& Elsevier]

Background: Early parental separation may be a stress factor causing a long-term alteration in the hypothalamic-pituitary-adrenal-axis activity possibly impacting on the susceptibility to develop overweight and obesity in offspring. We aimed to examine the body mass index (BMI) and the risk of overweight and obesity in children whose parents lived separately before the child was born., Methods: A follow-up study was conducted using data from the Aarhus Birth Cohort in Denmark and included 2876 children with measurements of height and weight at 9-11-years-of-age, and self-reported information on parental cohabitation status at child birth and at 9-11-years-of-age. Quantile regression was used to estimate the difference in median BMI between children whose parents lived separately (n = 124) or together (n = 2752) before the birth. We used multiple logistic regression to calculate odds ratio (OR) for overweight and obesity, adjusted for gender, parity, breast feeding status, and maternal pre-pregnancy BMI, weight gain during pregnancy, age and educational level at child birth; with and without possible intermediate factors birth weight and maternal smoking during pregnancy. Due to a limited number of obese children, OR for obesity was adjusted for the a priori confounder maternal pre-pregnancy BMI only., Results: The difference in median BMI was 0.54 kg/m2 (95% confidence intervals (CI): 0.10; 0.98) between children whose parents lived separately before birth and children whose parents lived together. The risk of overweight and obesity was statistically significantly increased in children whose parents lived separately before the birth of the child; OR 2.29 (95% CI: 1.18; 4.45) and OR 2.81 (95% CI: 1.05; 7.51), respectively. Additional, adjustment for possible intermediate factors did not substantially change the estimates., Conclusion: Parental separation before child birth was associated with higher BMI, and increased risk of overweight and obesity in 9-11-year-old children; this may suggest a fetal programming effect or unmeasured difference in psychosocial factors between separated and non-separated parents.

Today, most persons with Down syndrome (DS) survive into middle age, but information on their social conditions as adults is limited. We addressed this knowledge gap using data from national registers in Denmark. We identified a national cohort of 1,998 persons with DS who were born between 1968 and 2007 (1,852 with standard trisomy 21, 80 with Robertsonian translocations and 66 with mosaicism) using the Danish Cytogenetic Register. We followed this cohort from 1980 to 2007. Information on social conditions (education, employment, source of income, marital status, etc.) was obtained by linkages to national registers, including the Integrated Database for Longitudinal Labor Market Research. For those aged 18 and older, more than 80% of persons with DS attended 10 years of primary school, with about 2% completing secondary or post-secondary education. About 4% obtained a full-time job, whereas the remaining mainly received public support from the government. Only a few (1-2%) of persons with DS were married or had a child. No significant differences in these social conditions were seen between males and females. More persons with mosaic DS attended secondary or post-secondary education, had a full-time job, were married, or had a child (18%, 28%, 15%, and 7%, respectively), compared with persons with standard DS (1%, 2%, 1%, and 1%, respectively). These data may provide families with better insight into social conditions and society with a better understanding of the social support needed for persons with DS., (© 2013 Wiley Periodicals, Inc.)

Objectives: It has been suggested that maternal emotional stress during cardiogenesis may be a risk factor for congenital heart defects (CHD). We examined this association using bereavement around the time of conception as an indicator of maternal exposure to stress in a large registry-based study., Methods: We identified 1,770,878 singletons born in Denmark from January 1, 1978, to December 31, 2008. Of these, 44,820 children were born to mothers who had lost a first-degree relative during the time period from 1 year before their last menstrual period until delivery (6080 mothers lost a child or partner, and 38,740 mothers lost a parent or sibling). CHD diagnoses were identified from the Danish Registry of Congenital Heart Disease. We used logistic regression models to calculate prevalence odds ratios (ORs) of CHD for exposed children compared with unexposed children., Results: Exposed children had a slightly higher prevalence of CHD than unexposed children (0.94% vs 0.82%; adjusted OR = 1.11, 95% confidence interval 1.00-1.22). The association was most marked for children of mothers who had lost a child or partner (1.15% vs 0.82%; adjusted OR = 1.32, 1.04-1.67)., Conclusions: Prenatal exposure to severe emotional stress may slightly increase the prevalence of CHD in offspring.

Most persons with Down syndrome (DS) now survive to adulthood, but their health care needs beyond childhood are not well described. We followed a national cohort of 3,212 persons with DS and a reference cohort of persons without DS through the Danish National Hospital Register from January 1, 1977, to May 31, 2008. Poisson regression was used to calculate rate ratios for numbers of overnight hospital admissions and hospital days. During the study period, persons with DS had more than twice the rate of hospital admissions and nearly three times as many bed-days as the population as a whole. Malformations, diseases of the respiratory system, and diseases of the nervous system or sensory organs were the principal indications for hospital admissions. The higher rate ratios for hospital admissions were seen especially among persons less than 20 years of age. Hospitalizations for neoplasms or for diseases of the musculoskeletal system or connective tissue were much less frequent among adults with DS. As survival among persons with DS continues to improve, these findings are likely to be useful for health care planning, although the potential utility may be different for different health care systems., (Copyright © 2013 Wiley Periodicals, Inc.)

Cancer risk in parents may be related to congenital malformations (CMs) in their children if they share genetic susceptibility or environmental exposure that may be teratogenic and carcinogenic. We conducted a population-based cohort study based on Danish register data. We identified 795,607 mothers and 781,424 fathers who had all their children between 1977 and 2007 in Denmark. Information on CM was obtained from the Danish Hospital Registry and information on cancer was obtained from the Danish Cancer Registry. Parents were followed from the birth of their first child until the diagnosis of cancer, death, emigration, or December 31, 2007. We used Cox regression models to estimate hazard ratios (HRs) for cancer including cancer in specific organs in mothers and fathers. Overall, 75,701 (9.5%) mothers and 72,724 (9.3%) fathers had at least one child diagnosed with CMs within the first year of life. Neither mothers (HR=1.04; 95% CI: 0.99-1.04) nor fathers (HR=1.03; 95% CI: 0.98-1.09) who had a child with a CM had a higher overall risk of cancer. Mothers (HR=0.76, 95% CI: 0.58-1.00) or fathers (HR=0.89, 95% CI: 0.66-1.19) who had a child with a chromosomal malformation had a lower overall cancer risk. The findings also showed a higher risk for some specific types of cancer in parents who had children with a CM in the specific system. Some, or perhaps all, of these findings may be due to chance caused by multiple comparisons. We present all results on paper or online to provide clues for further research and to avoid publication bias., (© 2013 Wiley Periodicals, Inc.)

Purpose: Several studies have shown substantially longer survival among persons with Down syndrome in recent decades. We examined survival patterns among Danish persons with Down syndrome by karyotype., Methods: A national cohort of 3,530 persons with Down syndrome identified from the Danish Cytogenetic Register and a reference cohort of persons without Down syndrome randomly selected from the general population were followed from 1 April 1968 to 15 January 2009 by linkages to the Register of Causes of Death and the Civil Registration System., Results: Overall, persons with Down syndrome had higher mortality than the reference cohort but to a lesser degree for persons with mosaic trisomy 21 than for persons with standard trisomy 21 or with Robertsonian translocations (hazard ratio 4.98 (95% confidence interval 3.51-7.08), 8.94 (8.32-9.60), and 10.23 (7.50-13.97), respectively). Among persons with Down syndrome born after April 1968, more recent birth cohorts had lower mortality rates than older birth cohorts, which was largely due to declining mortality among persons with Down syndrome who also had congenital heart defects., Conclusion: Recent birth cohorts of persons with Down syndrome experienced declining mortality, likely due to treatment for congenital heart defects, and persons with mosaic trisomy 21 had better survival than persons with other Down syndrome karyotypes.

Background: Studies suggest that children born very preterm have a high risk of developmental coordination disorder (DCD). We examined the relation between the larger spectrum of gestational age at birth and the risk of DCD., Methods:   We used the 7-year follow-up data from 22898 singletons in the Danish National Birth Cohort. We calculated a total score from the Developmental Coordination Disorder Questionnaire (DCDQ), incorporated in the 7-year follow-up, and defined children with a score of 46 or below as having probable DCD. Information on gestational age was obtained from the Medical Birth Register., Results:   Gestational age at birth was inversely associated with the risk of DCD; a decline in gestational age by a week was associated with a 19% [95% confidence interval 14%, 25%] increased risk of DCD screening positive among children delivered before 40 weeks. No significant increased risk of DCD was seen for children born post-term., Conclusion: Our data indicate that short gestational age at birth in a range up to gestational week 37 is related to an increased risk of DCD., (© 2012 Blackwell Publishing Ltd.)

Behavioural patterns in children of infertile couples may be influenced by both the underlying causes of infertility and stress in the couples. Treatment procedures, such as culture media and manipulation of gametes and embryos, may also result in developmental problems. We examined behavioural problems in children as a function of infertility and infertility treatment, using data from three population-based birth cohorts in Denmark (Aalborg-Odense Birth Cohort, Aarhus Birth Cohort and Danish National Birth Cohort). Information on time to pregnancy and infertility treatment was collected during pregnancy. Children aged between 7 and 21 years were assessed using the Strengths and Difficulties Questionnaire (SDQ). The SDQ was completed by mothers in all cohorts and, in addition, by teachers in the Aarhus cohort and by children themselves in the Aalborg-Odense cohort. Children born after a time to pregnancy of >12 months and no infertility treatment had a behavioural pattern similar to children of fertile parents. Teachers reported a higher total difficulties score for children born after infertility treatment, but no significant differences were seen on any subscales of the teachers' report, and neither the mothers nor the children reported any differences on the total difficulties score and the prosocial behaviour score. Our results are thus overall reassuring regarding behavioural problems in children born to infertile couples, regardless of infertility treatment., (© 2011 Blackwell Publishing Ltd.)

Aims: To explore the relation between employment status, type of unemployment and pregnancy outcomes., Methods: A cohort study of 7,282 pregnancies of unemployed women and 56,014 pregnancies among women in paid jobs was performed within the Danish National Birth Cohort. Pregnancy outcomes were ascertained and information about lifestyle, occupational, medical, and obstetric factors was obtained. Logistic regression was used to calculate odds ratios (OR) for fetal loss, congenital anomalies, multiple births, sex ratio, preterm and very preterm birth and small for gestational age status, adjusting for lifestyle, medical and obstetric factors., Results: There were no differences in pregnancy outcomes between employed and unemployed women but women receiving unemployment benefit had an increased risk of preterm birth (adjusted OR (aOR) 1.16, 95% confidence interval (95% CI) 1.03-1.31) and having a small for gestational age child (aOR 1.08, 95% CI 1.00-1.19) compared with employed women. Women receiving sickness or maternity benefit had an increased risk of multiple birth (aOR 1.70, 95% CI 1.43-2.04), preterm (aOR 1.47, 95% CI 1.22-1.77) and very preterm birth (aOR 1.88, 95% CI 1.22-2.89), while those receiving an unreported type of support had an increased risk of preterm birth (aOR 1.40, 95% CI 1.02-1.93)., Conclusions: We found no indication that being unemployed during pregnancy benefits or endangers the health of the child. Within the subgroups of unemployed women, we observed that women receiving unemployment and sickness or maternity benefits were at higher risk for some adverse pregnancy outcomes.

Background: Children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of cerebral palsy (CP), perhaps due to the higher frequency of preterm birth, multiple births or vanishing embryo in the pregnancies. However, it has been suggested that the underlying infertility may be part of the pathway. In this study, we examined whether untreated subfecundity (measured by time to pregnancy) or infertility treatment was associated with an increased risk of CP in the offspring., Methods: Using the Danish National Birth Cohort (1997-2003), we compared children born after 0-2 months of waiting time to pregnancy (n = 35 848) with those born after a time to pregnancy of 3-5 months (n = 15 361), 6-12 months (n = 11 528) and >12 months (n = 7387), as well as those born after IVF/ICSI (n = 3617), ovulation induction with or without intrauterine insemination (n = 3000), and unplanned pregnancies (n = 13 462). CP cases were identified through the Danish CP Register., Results: In total, 165 (0.18%) children were diagnosed with CP in the entire cohort. We found no significant association between time to pregnancy and the risk of CP in children conceived spontaneously. Children born after IVF/ICSI had an increased risk of CP, even after adjustment for preterm birth and multiplicity (hazard ratio 2.30, 95% confidence interval 1.12-4.73)., Conclusions: Subfecundity per se did not appear to be associated with the risk of CP in children, whereas being born after IVF/ICSI conferred an increased risk.

Background: It has previously been reported that children born after infertility treatment had a slight delay in early motor milestones. In this study, we examined whether children of infertile couples with or without infertility treatment had a higher risk of developmental coordination disorder (DCD)., Methods: We used data on parental infertility and DCD among 23 167 singletons from the Danish National Birth Cohort (1996-2002). Data on time to pregnancy (TTP) and infertility treatment were collected early in pregnancy. Data on DCD in children were collected using the Developmental Coordination Disorder Questionnaire, filled in by the mothers during follow-up when the children were 7 years old. We used the recommended cut-off for the age group to classify children., Results: Compared with children born of fertile couples, children conceived after a waiting TTP of longer than 12 months had a slightly higher risk of DCD [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.03-1.77], but the estimated OR was not significant in children born after infertility treatment (OR 1.19, 95% CI 0.86-1.66). None of the individual treatment procedures was significantly associated with a higher risk of DCD. Children of parents who had not planned their pregnancy showed no elevated risk., Conclusions: Our findings are overall reassuring, although it is possible that low fecundity may be associated with a modestly increased risk of DCD.

In hospitals, women of reproductive age do a range of work tasks, some of which are known to carry potential risks. Tasks such as working with radiation, chemicals, and infectious agents, as well as performing heavy lifting or tasks requiring erratic sleep patterns have been reported to increase the risk of reproductive failures. Our aim was to study pregnancy outcomes in female hospital workers in Denmark. We performed a cohort study of 5976 female hospital workers and used as a reference group 60,890 women employed outside of hospitals. The reproductive health of hospital workers working during pregnancy is comparable to those of non-hospital workers for the majority of reproductive failures studied. However, an increased prevalence of congenital abnormalities was noted in some subgroups of hospital workers, which may indicate that some hospital work still entails fetotoxic hazards.

Babies born of infertile couples, regardless of treatment, have a higher risk of preterm birth and low birthweight, conditions associated with delayed development. We examined developmental milestones in singletons as a function of parental infertility [time to pregnancy (TTP) > 12 months] and infertility treatment. From the Danish National Birth Cohort (1997-2003), we identified 37 897 singletons born of fertile couples (TTP < or = 12 months), 4351 born of infertile couples conceiving naturally (TTP > 12 months), and 3309 born after infertility treatment. When the children were about 18 months old, mothers reported 12 developmental milestones by responding to structured questions. We defined a failure to achieve the assessed milestone or the minimal numbers of milestones in a summary (motor, or cognitive/language skills) as delay. Naturally conceived children born of infertile couples had a pattern of psychomotor development similar to that of children born of fertile couples, but increasing TTP correlated with a modest delay. When the analysis was restricted to infertile couples (treated and untreated), children born after treatment showed a slight delay in cognitive/language development (odds ratio 1.24, [95% confidence interval 1.01, 1.53]) for not meeting at least three out of six cognitive/language milestones); children born after intracytoplasmic sperm injection (ICSI) had the highest estimated relative risk of delay for most milestones, especially motor milestones. These results suggest that a long TTP may be associated with a modest developmental delay. Infertility treatment, especially ICSI, may be associated with a slight delay for some of these early milestones.

Background: Nonright-handedness, particularly mixed-handedness, has been associated with a number of medical conditions. We examined whether handedness was associated with fecundity, measured by time to pregnancy., Methods: We used data on parental handedness and time to pregnancy from 2 regional birth cohorts in Denmark: the Aalborg-Odense Birth Cohort (1984-1987) and the Aarhus Birth Cohort (1990-1992) (n = 5808 and 3426, respectively). We applied discrete-time survival analysis to assess fecundity in relation to handedness., Results: In both cohorts, we saw a slightly lower fecundity in individuals who reported being mixed-handed., Conclusions: Our data showed a modest association between mixed-handedness and subfecundity, which suggests that these traits may share a common etiology, perhaps tracing back to the prenatal period.

Background: Since paternal age correlates with some diseases that have a high case-fatality, a paternal age effect on offspring's survival is expected but unsettled. We examined the association between paternal age and mortality in children in a large population-based cohort taking maternal age and socioeconomic factors into account., Methods: From the Danish Fertility Database (1980-1996), we identified 102,879 couples and their firstborn singleton children. Information on childhood death (N = 831) was obtained by linking the cohort to the nationwide register on cause of death (1980-1998)., Results: We observed a U-shaped association between paternal age and the overall mortality rate in children up to 18 years of age. Adjustment for maternal age and other confounders reduced the mortality rate ratio (MRR) for children of younger fathers but not for children of older fathers. Compared with children of fathers aged between 25 and 29 years, the adjusted MRR was 1.77 (95% confidence interval 1.28-2.45) for children of fathers aged between 45 and 49 years and 1.59 (1.03-2.46) for children of fathers aged 50 years or more. The cause-specific MRRs were highest for congenital malformations [2.35 (1.42-3.88)] and injury or poisoning [3.43 (1.49-7.92)] for children of fathers aged 45 years or more., Conclusion: Our data revealed a higher mortality in offspring of fathers aged 45 years or more that lasted into adulthood. This adds to the cumulating evidence on adverse effects of advanced paternal age in procreation.

Objective: To examine the association between infertility, with or without treatment, and fetal growth, as well as perinatal and infant mortality., Methods: From the Danish National Birth Cohort (1997-2003), we identified 51,041 singletons born of fertile couples (time to pregnancy 12 months or less), 5,787 born of infertile couples conceiving naturally (time to pregnancy more than 12 months), and 4,317 born after treatment. We defined small for gestational age (SGA) as the lowest 5% of birth weight by sex and gestational age., Results: Crude estimates suggested an increased risk of perinatal mortality and SGA among infertile couples (treated and untreated), but the odds ratios (ORs) of perinatal mortality among infertile couples were attenuated after adjustment for maternal age and body mass index (1.32, 95% confidence interval [CI] 0.95-1.84 among untreated and 1.26, 95% CI 0.86-1.85 among treated couples). The elevated risk of SGA among infertile couples persisted after adjustment for maternal age, parity, and smoking (OR 1.24, 95% CI 1.10-1.40 among untreated, and OR 1.40, 95% CI 1.23-1.60 among treated). The risk of SGA increased with time to pregnancy, and a longer time to pregnancy was associated with a small reduction in birth weight across the whole distribution., Conclusion: The increased risk of SGA observed among infertile couples with or without infertility treatment suggests that infertility may be a risk factor for intrauterine growth restriction. Treatment per se may have little effect on fetal growth. A small-to-moderate increased risk of perinatal mortality in infertile couples cannot be ruled out due to the small number of cases., Level of Evidence: II.

Background: We have previously observed that an increasing time to pregnancy (TTP) is associated with a reduced frequency of twin deliveries in couples not receiving infertility treatment. By using updated information, we assessed the frequencies of dizygotic (DZ) and monozygotic (MZ) twin deliveries as a function of infertility (TTP > 12 months), as well as infertility treatment., Methods: From the Danish National Birth Cohort (1997-2003), we identified 51 730 fertile couples with TTP 12 months and 5163 infertile couples who conceived after treatment. Information on zygosity, available for part of the cohort (1997-2000), was based on standardized questions on the similarities between the twins at the age of 3-5 years., Results: Compared with fertile couples, the frequency of DZ twin deliveries was lower for infertile couples conceiving naturally (odds ratio 0.4, 95% confidence interval 0.2-0.7) and was much higher for infertile couples conceiving after treatment (17.3, 14.4-20.7). The frequency of DZ twin deliveries decreased with TTP in untreated couples, whereas the frequency of MZ twin deliveries remained constant., Conclusions: The frequency of DZ twin deliveries decreased with TTP and substantially increased with infertility treatment, whereas MZ twin deliveries remained substantially unchanged.

Background: Only few studies have addressed the long-term neurological outcomes of children born by subfertile couples. We studied the risk of epilepsy and febrile seizures in children of treated and untreated subfertile couples., Methods: The study included 83 194 live singletons born by mothers who took part in the Danish National Birth Cohort (DNBC). Information on time to pregnancy (TTP) and infertility treatment was reported by the mothers in computer-assisted telephone interviews. Data on epilepsy and febrile seizures were extracted from the Danish National Hospital Register., Results: Overall, children of subfertile couples (TTP > 12 months) had a 51% higher risk of epilepsy [incidence rate ratio (IRR): 1.51; 95% confidence interval (95% CI): 1.17-1.94] compared with children of couples with a TTP of 0-5 months. The corresponding estimates were 1.71 (95% CI: 1.21-2.42) if the couples had received infertility treatment and 1.38 (95% CI: 1.00-1.89) if they conceived spontaneously. Children of subfertile couples did not have a higher risk of febrile seizures except for those who received hormonal treatment (HT) with or without intrauterine insemination (IRR = 1.37; 95% CI: 1.14-1.66)., Conclusions: Children of subfertile couples had a slightly increased risk of epilepsy, and the risk tended to be higher for children of couples who received infertility treatment. Whether this reflects side effects of treatment or severity of subfecundity is not known.

Objectives: To examine whether infertile couples (with a time to pregnancy of > 12 months), who conceive naturally or after treatment, give birth to children with an increased prevalence of congenital malformations., Design: Longitudinal study., Setting: Danish national birth cohort., Participants: Three groups of liveborn children and their mothers: 50,897 singletons and 1366 twins born of fertile couples (time to pregnancy < or = 12 months), 5764 singletons and 100 twins born of infertile couples who conceived naturally (time to pregnancy > 12 months), and 4588 singletons and 1690 twins born after infertility treatment., Main Outcome Measures: Prevalence of congenital malformations determined from hospital discharge diagnoses., Results: Compared with singletons born of fertile couples, singletons born of infertile couples who conceived naturally or after treatment had a higher prevalence of congenital malformations-hazard ratios 1.20 (95% confidence interval 1.07 to 1.35) and 1.39 (1.23 to 1.57). The overall prevalence of congenital malformations increased with increasing time to pregnancy. When the analysis was restricted to singletons born of infertile couples, babies born after treatment had an increased prevalence of genital organ malformations (hazard ratio 2.32, 1.24 to 4.35) compared with babies conceived naturally. No significant differences existed in the overall prevalence of congenital malformations among twins., Conclusions: Hormonal treatment for infertility may be related to the occurrence of malformations of genital organs, but our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants. The association between untreated infertility and congenital malformations warrants further examination.

Background: New evidence suggests that advanced paternal age is a reproductive hazard, but we do not know whether paternal age affects the physical conditions of newborn infants as measured by the Apgar score., Methods: We conducted a register-based cohort study of 70,347 couples and their first singleton infants by using data from the Danish Fertility Database (1980-1996). Information on Apgar score was obtained by linking the children to the National Birth Register., Results: The odds ratio for having a baby with a 1-minute Apgar score of 1-3 was 1.64 (95% confidence interval = 1.08-2.48) for fathers 45 to 49 years of age and 1.49 (0.76-2.94) for fathers 50+ years compared with fathers 20 to 29 years (P for trend = 0.011). The risk of having a 5-minute Apgar score less than 7 increased among fathers 45+ years old (P for trend = 0.178)., Conclusions: Our data suggest a modest effect of advanced paternal age on the Apgar score.

Objective: We conducted a follow-up study to examine whether exposure to pesticides during pregnancy had an adverse effect on pregnancy outcomes among Danish gardeners and farmers., Methods: Using data from the National Birth Cohort in Denmark, we identified 226 pregnancies of gardeners and 214 pregnancies of farmers during 1997 through 2003. Work activities and exposure to pesticides were reported in an interview (around 16 weeks of gestation). Totally, 62,164 other workers in the cohort served as a reference group. Pregnancy outcomes were obtained by linkage to the national registers. Cox regression was applied to analyze late fetal loss and congenital malformations, and logistic regression was used to analyze preterm birth and small for gestational age., Results: There were no significant differences in the studied pregnancy outcomes between gardeners or farmers and all other workers, except for an increased risk of very preterm birth for gardeners and a favorable birth weight for farmers. With the exception of biologic approach used in gardening, neither work activities nor exposure to pesticides showed a significant increased risk of adverse birth outcomes among gardeners or farmers., Conclusions: Our data suggest little effect of occupational exposures to pesticides on pregnancy outcomes among gardeners or farmers in Denmark. The results may not apply to other countries.

Objectives: The Danish National Birth Cohort (DNBC) was used to examine pregnancy outcomes among female hairdressers and neurodevelopment in their offspring., Methods: A population-based cohort study was conducted of 550 hairdressers and 3216 shop assistants (reference group) by using data from the Danish National Birth Cohort between 1997 and 2003. Information on job characteristics was reported by the women in the first interview (around 17 weeks of gestation). Pregnancy outcomes were obtained by linkage to the national registers. Developmental milestones were reported by the mother at the fourth interview, when the child was approximately 19 months old. Cox regression was applied to analyze fetal loss and congenital malformation. Logistic regression was used to analyze other pregnancy outcomes and developmental milestones., Results: We found no significant differences in fetal loss, multiple births, gender ratio, preterm birth, small-for-gestational age, congenital malformations, or achievement of developmental milestones among the children of hairdressers and shop assistants., Conclusions: The results do not indicate that children of hairdressers in Denmark currently have a high risk of fetal impairment or delayed psychomotor development.

Background: Spontaneous mutations in germ cells increase with male age, but an association between paternal age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association., Methods: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71937). Diagnoses of congenital malformations in children were obtained by linkage to the nationwide hospital register (1980-1999)., Results: Overall, there were no differences in the prevalence of malformations as a function of paternal age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Down's syndrome, increased with increasing paternal age. For example, in comparison with fathers age 20-29 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.81-1.65] for age 35-39 years, 1.33 (95% CI 0.79-2.25) for age 40-44 years, 1.73 (95% CI 0.82-3.65) for age 45-49 years, and 3.20 (95% CI 1.37-7.48) for age > or = 50 years (test for trend P = 0.01)., Conclusions: Our data suggest that advanced paternal age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of the gametes in men induced by biological or environmental factors.

Objectives: The Danish National Birth Cohort was used to examine whether laboratory work was associated with reduced fecundity., Methods: Self-reported data on laboratory work and waiting time to pregnancy (0-2, 3-5, 6-12 and > 12 months) were used for 829 female laboratory technicians interviewed in 1997-2003. Altogether 6250 female teachers formed the reference group. A discrete-time survival analysis with a complementary log-log link was applied to estimate the fecundability ratio between the exposed and unexposed women, with adjustment for maternal age, gravidity, smoking, prepregnancy body mass index, and paternal job., Results: No difference in time to pregnancy was found between the laboratory technicians and teachers or between the laboratory technicians with different exposures. The adjusted fecundability ratio for the laboratory technicians was 0.94 [95% confidence interval (95% CI) 0.86-1.02] for all pregnancies and 0.98 (95% CI 0.86-1.13) for first pregnancies. A healthy worker effect was found for the laboratory technicians working with the work processes under study., Conclusions: The results do not suggest that laboratory work in Denmark at present impairs female fecundity.

Background: There is growing evidence that advanced paternal age can be a reproductive hazard., Methods: We studied couples and their first children using nationwide registers in Denmark between 1980 and 1996. We restricted the analysis to mother's age 20-29 years. We estimated odds ratios (ORs) of preterm (< 37 weeks gestation) and very preterm birth (< 32 weeks) as a function of paternal age using logistic regression to adjust for potential confounding variables., Results: The risk of preterm birth increased with paternal age, almost entirely resulting from an association for very preterm birth. Compared with fathers age 20-24 years, ORs for very preterm birth were 1.3 (age 25-29), 1.4 (age 35-39), 1.7 (age 40-44), 1.6 (age 45-49), and 2.1 (age 50+) (test for trend: P = 0.01)., Conclusions: Risk of very preterm birth increases among older fathers, perhaps as a result of a paternal placental effect.

Objective: The Danish National Birth Cohort (DNBC) was used to examine whether shift work or job stress correlate with late fetal loss., Methods: We identified 33,694 pregnancies of daytime workers and 8,075 pregnancies of shift workers in women recruited to the DNBC between 1998 and 2001. Pregnancy outcomes were obtained by linkages to the national registers. Hazard ratios of fetal loss were calculated by using Cox regressions with left truncation., Results: Fixed night work was associated with fetal loss (hazard ratio = 1.85, 95% confidence interval = 1.00-3.42). No high risk of fetal loss was seen for other types of shift work. Job stress, as measured in our study, was not associated with fetal loss., Conclusions: Our results suggest that fixed night work during pregnancy increases the risk of late fetal loss.

Objective: We used the Danish National Birth Cohort to estimate the effect of shift work on the duration of pregnancy and birth weight., Study Design: In the Danish National Birth Cohort (1998-2001), we identified women (and their singleton births): 32465 women with daytime work, 1038 women with fixed evening work, 400 women with fixed night work, 3137 women with rotating shift work (without night), and 3197 women with rotating shift work (with night) during pregnancy (first and second trimester). Birth outcomes were collected by linkage to the Central Population Register, the National Patient Register, and the National Birth Register. Gestational age at birth and birth weight were analyzed by means of general linear regression and logistic regression., Results: Mean gestational age at birth and birth weight at term for daytime work were 281 days and 3616 g, although 281 days and 3586 to 3626 g for shift work. There were no statistically significant differences in gestational age at birth or birth weight at term between any types of shift work and daytime work. Fixed night work had a high risk of postterm birth (odds ratio, 1.35; 95% CI, 1.01-1.79); fixed evening work had a high risk of full-term low birth weight (odds ratio, 1.80; 95% CI, 1.10-2.94); and shift work as a group showed a slight excess of small-for-gestational-age babies (odds ratio, 1.09; 95% CI, 1.00-1.18). The risk of postterm birth was modified by maternal occupation. Industrial workers with fixed night work had a high risk of postterm birth., Conclusion: Our results suggest that shift work during pregnancy had limited effects on indicators of fetal growth. Night work may prolong the duration of pregnancy and reduce fetal growth, especially among industrial workers.