The purpose of this nested case-control study in Denmark was to study the association between use of corticosteroids and risk of miscarriage.
We identified prescriptions for corticosteroids before the miscarriage/index date. We estimated odds ratios (ORs) for miscarriage and for early (<13 weeks) and late (13–21 weeks) miscarriage adjusting for age, history of diabetes and epilepsy, and nonsteroidal anti-inflammatory drug use.
We identified 10,974 women with miscarriage and 109,740 controls. Prevalence of inhaled corticosteroid use within 60 days before the index date was 1.3% among the cases and 1.0% among the controls (OR = 1.20; 95% confidence interval [CI] 1.01–1.44). Prevalence of oral corticosteroid use within 60 days before the index date was 0.3% for both cases and controls (OR = 0.78; 95% CI 0.53–1.15). For inhaled and oral corticosteroids, the ORs of early miscarriage were 1.22 (95% CI 1.01–1.49) and 0.81 (95% CI 0.55–1.20), respectively.
Use of inhaled corticosteroids was associated with a slightly increased risk of early miscarriage, but explanations alternative to causal ones were possible.
case-control study; corticosteroid hormones; epidemiology; miscarriage
Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P < 5 × 10−8) for ‘age at first tooth’ and 11 loci for ‘number of teeth’. Together, these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P = 9.080 × 10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.
Background and Purpose:
Many researchers acknowledge the importance of “training errors” as the main cause of running‐related injuries. The purpose of this clinical commentary is to present a theoretical framework for the assumption that some running‐related injuries among rear‐foot strikers develop due to rapidly changing running volume, while others develop due to rapidly changing running pace.
Description of Topic with Related Evidence:
Evidence from clinical and experimental studies is presented to support the assertion that rapid change in running volume may lead to the development of patellofemoral pain syndrome, iliotibial band syndrome, and patellar tendinopathy, while change in running pace may be associated with the development of achilles tendinopathy, gastrocnemius injuries, and plantar fasciitis.
Discussion/Relation to Clinical Practice:
If this assertion is correct, bias may be prevented in future studies by categorizing injuries into volume or pacing injuries. However, more work is needed to provide further evidence in support of this approach. Future investigations of the link between training patterns and injury development should be designed as large‐scale prospective studies using objective methods to quantify training patterns.
Level of evidence:
Etiology; running pace; running‐related injury; training volume
Medications may be consumed periconceptionally before a woman knows she is pregnant. In this study, the authors evaluate the association of a prescription diet drug (Letigen) containing ephedrine (20 mg) and caffeine (200 mg) with spontaneous abortion (SAB) in the Danish National Birth Cohort.
Women were recruited during their first prenatal visit from 1996–2002. Pre-conception and early pregnancy medication use was reported on the enrollment form, and pregnancy outcome was determined by linking the mother's Civil Registration Number to the Medical Birth Registry and the National Hospital Discharge Register. Of 97,903 eligible pregnancies, 4,443 ended in SAB between 5 and 20 completed gestational weeks, inclusive. Letigen use was reported for 565 pregnancies. Cox regression models accounting for left truncation were fit to estimate the effect of pre-conception and early pregnancy Letigen use on SAB.
The estimated maternal age-adjusted hazard ratio for SAB was 1.1 (95% confidence interval 0.8–1.6) for any periconceptional Letigen use compared to no periconceptional use.
Although Letigen has high levels of caffeine (the recommended 3 pills/day are approximately equivalent to caffeine from 6 cups of coffee), periconceptional use does not appear to be associated with an appreciably increased hazard of clinically recognized SAB.
The aim of the present study was to identify predictors of nonparticipation in a Danish cohort of individuals on long-term sickness absence with a nonparticipation rate of 53.6%.
Data from Danish public registers were linked to all 2414 individuals initially recruited to the cohort. Information regarding social- and health-related characteristics was retrieved. Adjusted logistic regression was carried out to examine differences between participants and nonparticipants as well as to identify predictors of nonparticipation.
Nonparticipation was associated with being male, relatively young, having a vocational secondary education, and having a low income, whereas a recent somatic disease treated in hospital was a predictor for participation. Having had a psychiatric disorder in the past was generally a barrier for participation, while a recent psychiatric disorder was a positive factor for participation.
Individuals with low socioeconomic status and individuals with prior psychiatric disorders were less willing to participate in this cohort study of long-term sickness absence.
mental disorders; nonparticipation; nonresponse; sickness absence
Maternal smoking during pregnancy is associated with low birth weight. Common variation
at rs1051730 is robustly associated with smoking quantity and was recently shown to
influence smoking cessation during pregnancy, but its influence on birth weight is not
clear. We aimed to investigate the association between this variant and birth weight of
term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European
origin study participants by smoking status (women who smoked during pregnancy versus
women who did not smoke during pregnancy) and, in each stratum, analysed the association
between maternal rs1051730 genotype and offspring birth weight. There was evidence of
interaction between genotype and smoking (P = 0.007). In women who
smoked during pregnancy, each additional smoking-related T-allele was associated with a 20
g [95% confidence interval (95% CI): 4–36 g] lower birth weight
(P = 0.014). However, in women who did not smoke during
pregnancy, the effect size estimate was 5 g per T-allele (95% CI:
−4 to 14 g; P = 0.268). To conclude, smoking status
during pregnancy modifies the association between maternal rs1051730 genotype and
offspring birth weight. This strengthens the evidence that smoking during pregnancy is
causally related to lower offspring birth weight and suggests that population
interventions that effectively reduce smoking in pregnant women would result in a reduced
prevalence of low birth weight.
To assess whether onset of rheumatoid arthritis (RA) prior to conception is associated with a delayed time to pregnancy (TTP).
The study included pregnant women from across Denmark enrolled in the Danish National Birth Cohort (DNBC) between 1996 and 2002, who had planned or partly planned the cohort pregnancy. RA diagnosis was identified using the Danish National Hospital Discharge Registry. Self-reported data including TTP, maternal age, parity, pre-pregnancy height and weight, maternal occupational status, smoking and alcohol consumption were collected using a detailed computer-assisted telephone interview at approximately 16 weeks of gestation. We used logistic regression analyses as well as a complementary log regression model to examine whether TTP was influenced by RA, adjusting for the above-mentioned variables.
Overall, compared to women with no recorded RA (n=68,170), women with prevalent RA (onset prior to conception) (n=112) were slightly older (30.8±4.3 vs. 29.7±4.1 years), were more likely to have been treated for infertility (9.8% vs. 7.6%) and were more likely to have taken longer than 12 months to conceive (25.0% vs. 15.6%). The association between RA and TTP was borderline significant after adjusting for covariates in the regression analyses (OR=1.6, 95% CI: 1.0, 2.4). Similar results were obtained after restricting the analyses to women who had planned the pregnancy or those who were nulliparous before the cohort pregnancy.
Women with RA onset prior to conception had a slightly longer TTP compared to those who did not have RA, indicating a slight reduction in fecundity.
To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring.
We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5–3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6–3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1–1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1–1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1–2.2) and the elevated risk remained after excluding children with congenital malformations.
This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming.
Background. Maternal distress during pregnancy increases the intrauterine level of glucocorticoids, which may have long-term health consequences for the child.
Objective. To examine if distress as a combined measure of anxiety, depression, and stress of the mother during pregnancy was associated with offspring childhood overweight at age 7.
Methods. We performed a cohort study using prospective data from 37,764 women and child dyads from the Danish National Birth Cohort (1996–2002). At a telephone interview at approximately 30 weeks gestation, the women reported whether they felt anxious, depressed, or stressed. The 95 percentile for body mass index in an international reference defined childhood overweight at any given age. Logistic regression was used for the analyses. Results. The prevalence of overweight children at 7 years of age was 9.9%. Prenatal exposure to maternal distress during pregnancy was not associated with childhood overweight at 7 years of age (adjusted OR 1.06 (95% CI 0.96; 1.18)). In analyses stratified on sex, a small tendency of overweight was seen in boys (OR 1.15 (0.99; 1.33)), but not in girls (OR 0.98 (0.85; 1.13)). Conclusions. Maternal distress during pregnancy appeared to have limited, if any, influence on the risk of overweight in offspring at 7 years of age.
Exposures during fetal life may have long-term health consequences including risk of childhood overweight. We investigated the associations between maternal recreational exercise during early and late pregnancy and the children's body mass index (BMI) and risk of overweight at 7 years. Data on 40,280 mother-child pairs from the Danish National Birth Cohort was used. Self-reported information about exercise was obtained from telephone interviews around gestational weeks 16 and 30. Children's weight and height were reported in a 7-year follow-up and used to calculate BMI and overweight status. Data was analyzed using multiple linear and logistic regression models. Recreational exercise across pregnancy was inversely related to children's BMI and risk of overweight, but all associations were mainly explained by smoking habits, socioeconomic status, and maternal pre-pregnancy BMI. Additionally, we did not find exercise intensity or changes in exercise habits in pregnancy related to the children's BMI or risk of overweight.
Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations.
From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ∼212,000 individuals). We followed up novel (at the time of the study) association signals (p<0.001) from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n = 20,917) and a population-based cohort of 15-year-old British adolescents (n = 2,418). Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P<5×10−8; FTO, MC4R and FAIM2). We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p<0.001), and nominal association (p<0.05) at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations.
Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all individuals in large population-based studies, which may require tens of thousands of subjects to achieve similar power.
The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P<5×10−8 and were replicated in four independent study groups from the United States and Denmark with a total of 3,762 individuals; all combined P-values were below 10−11. Two loci agreed with previous findings in primary tooth eruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9–4.1) fewer permanent teeth than children with 0 or 1 of these alleles.
While genome-wide association studies (GWAS) initially focused on the disease under investigation, additional findings in secondary traits have shown further benefits of having extensive phenotype data at hand. Using records from the nationwide dental registry for children and genotype data from two GWAS, we were able to identify four genomic loci associated with permanent tooth eruption in children. Two of the identified genomic regions had no previous GWAS findings, whereas two loci were reported in the context of primary dentition. A follow-up in an on-going GWAS showed that rs7924176 also plays a substantial role in primary dentition. During the age period of permanent tooth eruption many important developmental processes take place. Thus, we suggest following up the four reported SNPs in other growth-related traits to further elucidate the genetic background of maturation.
Preterm birth (PTB) has been associated with a later increased risk of maternal cardiovascular disease (CVD). We hypothesized a more pronounced relation between early or recurrent PTB and maternal CVD risk.
We related PTB severity (earlier gestational age at delivery) and recurrence (=2) among women with births from 1973–1983 in Denmark (n=427,765) to maternal CVD morbidity or mortality (1977–2006). Birth data were linked to CVD hospitalizations and deaths identified in national registers and data were analyzed using Cox proportional hazards models.
Women with a prior PTB had excess CVD after adjustment for age, parity, and education (HR 1.36 [95% CI 1.31, 1.41]). This was only modestly attenuated when women with preeclampsia or small for gestational age births were excluded, and the relationship was stronger for CVD mortality (HR 1.98 [1.73, 2.26]). Recurrent PTB was associated with higher CVD morbidity compared to women with one PTB, particularly for ischemic events (HR 1.78 [1.40, 2.27] vs. 1.22 [1.09, 1.36]). Risk was similarly elevated among women with early, moderate, and late PTB. Sensitivity analysis suggested that confounding by smoking only partly explained these associations.
Women with PTB, especially recurrent PTB, were at increased risk for CVD, suggesting common causes of these conditions.
Premature birth; cardiovascular disease; pregnancy; women
To describe patterns of prescribed drug use over time among primiparous women in Denmark.
Through the Danish Medical Birth Registry, we identified all primiparous women giving live birth or stillbirth at ≥ 22 gestational weeks in northern Denmark, from 1999 to 2009. From the Aarhus University Prescription Database we obtained information on the women’s prescriptions for reimbursed drugs filled from 30 days before conception until delivery.
Among 85,710 primiparous women, 47,982 (56.0%) redeemed at least one prescription from 30 days before conception until delivery. Women aged 35 years and older had the highest overall prevalence of prescription drug use (61.1%). Age-standardized prevalence of drug use was 54.7% in 1999 and 61.2% in 2009, prevalence ratio (PR) of 1.13 (95% confidence interval 1.10; 1.16), adjusted for age and smoking.
Over the 11-year period from 1999 to 2009, we found a modest increase in overall use of drugs by primiparous women in Denmark. This increase was not, however, explained by an increasing proportion of older first-time mothers. We noted changes in patterns of use of anti-infective drugs and antidepressants.
drug utilization; epidemiology; pregnancy
Exposure to infectious pathogens is a frequent occupational hazard for women who work with patients, children, animals or animal products. The purpose of the present study is to investigate if women working in occupations where exposure to infections agents is common have a high risk of infections and adverse pregnancy outcomes.
We used data from the Danish National Birth Cohort, a population-based cohort study and studied the risk of Infection and adverse outcomes in pregnant women working with patients, with children, with food products or with animals. The regression analysis were adjusted for the following covariates: maternal age, parity, history of miscarriage, socio-occupational status, pre-pregnancy body mass index, smoking habit, alcohol consumption.
Pregnant women who worked with patients or children or food products had an excess risk of sick leave during pregnancy for more than three days. Most of negative reproductive outcomes were not increased in these occupations but the prevalence of congenital anomalies (CAs) was slightly higher in children of women who worked with patients. The prevalence of small for gestational age infants was higher among women who worked with food products. There was no association between occupation infections during pregnancy and the risk of reproductive failures in the exposed groups. However, the prevalence of CAs was slightly higher among children of women who suffered some infection during pregnancy but the numbers were small.
Despite preventive strategies, working in specific jobs during pregnancy may impose a higher risk of infections, and working in some of these occupations may impose a slightly higher risk of CAs in their offspring. Most other reproductive failures were not increased in these occupations.
We investigated associations between maternal postpartum distress covering anxiety, depression and stress and childhood overweight.
We performed a prospective cohort study, including 21 121 mother-child-dyads from the Danish National Birth Cohort (DNBC). Maternal distress was measured 6 months postpartum by 9 items covering anxiety, depression and stress. Outcome was childhood overweight at 7-years-of age. Multiple logistic regression analyses were performed and information on maternal age, socioeconomic status, pre-pregnancy BMI, gestational weight gain, parity, smoking during pregnancy, paternal BMI, birth weight, gestational age at birth, sex, breastfeeding and finally infant weight at 5 and 12 month were included in the analyses.
We found, that postpartum distress was not associated with childhood risk of overweight, OR 1.00, 95%CI [0.98–1.02]. Neither was anxiety, depression, or stress exposure, separately. There were no significant differences between the genders. Adjustment for potential confounders did not alter the results.
Maternal postpartum distress is apparently not an independent risk factor for childhood overweight at 7-years-of-age. However, we can confirm previous findings of perinatal determinants as high maternal pre-pregnancy BMI, and smoking during pregnancy being risk factors for childhood overweight.
The timing and frequency of periconceptional multivitamin use may be related to the risk of preeclampsia. Women in the Danish National Birth Cohort (1997–2003) reported multivitamin or folate-only supplement use during a 12-week periconceptional period (from 4 weeks prior to 8 weeks after the last menstrual period). Preeclampsia cases were identified by using International Classification of Diseases, Tenth Revision, codes. Cox regression was used to estimate the association of frequency (weeks of use) and timing (preconception and postconception) of use with preeclampsia risk. Overall, there were 668 cases of preeclampsia (2.3%), and 18,551 women (65%) reported periconceptional multivitamin use. After adjustment, regular use (12 of 12 weeks) was related to a reduced risk of preeclampsia among normal-weight women. Compared with nonusers with a body mass index of 22 kg/m2, regular multivitamin users with the same body mass index had a 20% reduced risk of preeclampisa (hazard ratio = 0.78, 95% confidence interval: 0.60, 0.99). In addition, regular use in the postconception period only was associated with reduced risk, a relation that also appeared to be limited to women with a body mass index of <25 kg/m2 (hazard ratio = 0.63, 95% confidence interval: 0.42, 0.93). Folate-only supplement use was unrelated to preeclampsia risk. Regular periconceptional multivitamin use was associated with a reduced risk of preeclampsia among normal-weight women, and the immediate postconception period appeared to be the relevant exposure window.
body mass index; dietary supplements; pre-eclampsia; pregnancy; vitamins; women
The reproductive health of children born of infertile couples may be affected by infertility treatment or factors associated with infertility. We examined sexual maturation in children of parents with infertility.
We used data from a follow-up of 3382 girls and 2810 boys born between 1984 and 1987 in the Aalborg–Odense Birth Cohort. We had mothers’ report of time to pregnancy (TTP) and infertility treatment (at the time, mostly hormonal) from the pregnancy questionnaire administered in 1984–1987, and the children’s report of their own sexual maturation from the follow-up questionnaire administered in 2005, when they were between 18 and 21 years old. Many reported age only in year when they had the events related to sexual maturation, and for each event, we imputed the month based on the median month at each year of age among those reporting both years and months.
In girls, the mean age at menarche was 13.3 years and, in boys, the mean age at appearance of acne, voice break, regular shaving and first nocturnal emission were 14.5, 14.5, 17.2 and 14.7 years, respectively. We saw no significant differences in age at these events among children born of either fertile (with TTP of 0–12 months and no treatment), untreated infertile (with TTP of more than 12 months and no treatment) or treated infertile couples (with a history of examination or treatment for infertility).
Our data suggest no significant association between parental infertility or hormonal treatment and timing of sexual maturation in the offspring.
infertility; infertility treatment; puberty; time to pregnancy
Little is known about reproductive health in severely obese women. In this study, we present associations between different levels of severe obesity and a wide range of health outcomes in the mother and child.
From the Danish National Birth Cohort, we obtained self-reported information about prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly selected women from the remaining cohort who served as a comparison group. Information about maternal and infant outcomes was also self-reported or came from registers. Logistic regression was used to estimate the association between different levels of severe obesity and reproductive outcomes.
Subfecundity was more frequent in severely obese women, and during pregnancy, they had an excess risk of urinary tract infections, gestational diabetes, preeclampsia and other hypertensive disorders which increased with severity of obesity. They tended to have a higher risk of both pre- and post-term birth, and risk of cesarean and instrumental deliveries increased across obesity categories. After birth, severely obese women more often failed to initiate or sustain breastfeeding. Risk of weight retention 1.5 years after birth was similar to that of other women, but after adjustment for gestational weight gain, the risk was increased, especially in women in the lowest obesity category. In infants, increasing maternal obesity was associated with decreased risk of a low birth weight and increased risk of a high birth weight. Estimates for ponderal index showed the same pattern indicating an increasing risk of neonatal fatness with severity of obesity. Infant obesity measured one year after birth was also increased in children of severely obese mothers.
Severe obesity is correlated with a substantial disease burden in reproductive health. Although the causal mechanisms remain elusive, these findings are useful for making predictions and planning health care at the individual level.
Evidence relating chronic hypertension to risk of small for gestational age (SGA) births is conflicting. To identify factors associated with SGA that may involve a placental pathogenesis, we related chronic hypertension and other maternal factors that may be markers of endothelial dysfunction to preterm compared with term SGA births.
Chronic hypertension, diabetes, body mass index, age, and subfertility were related to risk of term and preterm SGA births in the Danish National Birth Cohort (n=81,008). SGA births were those with a birth weight adjusted for gestational age greater than 2 standard deviations below the mean based on fetal growth curves.
Risk of preterm SGA increased 5.5-fold (95% CI 3.2-9.4) and risk of term SGA increased 1.5-fold (1.0-2.2) among women with definite chronic hypertension. Risk of preterm SGA but not term SGA was increased among women less than 20 (odds ratio [OR] 2.8, 95% CI: 1.1-6.8) or greater than 36 (OR 2.0 , 95% CI:1.3-3.1) years of age and among those with at least 2 early spontaneous abortions (OR 2.0, CI:1.3-3.3). Smoking, parity, time to pregnancy greater than 12 months, and underweight status were similarly related to term and preterm SGA. Overweight status, obesity, and presence of diabetes were unrelated to either SGA subtype.
Chronic hypertension, young or older maternal age, and recurrent early spontaneous abortions increased risk for preterm SGA. These factors may involve abnormal placentation and likely represent a pathogenesis distinct from that leading to term SGA.
Background: The aim of this study is to investigate the association between socio-occupational status and the frequency of major congenital anomalies in offspring. Methods: The study population comprised 81 435 live singletons born to mothers enrolled in the Danish National Birth Cohort between 1996 and 2002. A total of 3352 cases of major congenital anomalies (EUROCAT criteria) were identified by linkage to the National Hospital Discharge Register. Malformations were recorded at birth or in the first year of life. Information about maternal and paternal socio-occupational status was collected prospectively using telephone interviews in the second trimester of pregnancy and was categorized as high, middle or low. Associations were measured as relative prevalence ratios using the highest socio-occupational status within the couple as the reference group. Results: The prevalence of all recorded major congenital anomalies was similar, about 4%, in all the socio-occupational categories. Low social status of the couple did, however, correlate with a higher prevalence of congenital anomalies of the ‘respiratory system’. No association was substantially attenuated when we adjusted for maternal and paternal age, smoking status, maternal alcohol habits, folic acid intake and body mass index. When malformations of the heart and the cardiovascular system were grouped together, they were more frequent in families where both parents presented a low socio-occupational status. Conclusion: We detected an association between low socio-occupational status and congenital anomalies of the respiratory system, the heart and the circulatory system. These malformations are good candidates for a large study on occupational, environmental and social determinants.
congenital anomalies; environmental risk factors; social status