A M Nybo Andersen

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population‐based study in six European regions

To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population‐based databases.

Time is on whose side? Time trends in the association between maternal social disadvantage and offspring fetal growth. A study of 1 409 339 births in Denmark, 1981–2004

Background: Fetal growth is highly socially patterned and is related to health across the life course, but how the social patterns of fetal growth change over time remains understudied. The time trends in maternal social disadvantage in relation to fetal growth were examined in the context of a universal welfare state under changing macroeconomic conditions over a 24-year period. Methods: All births in Denmark from 1981 to 2004 were included, and the association between maternal social disadvantage and birthweight was examined for gestational age z-scores over time using linear regression. Results: All measures of social disadvantage were associated with decreased fetal growth (p<0.001), but with considerable differences in the magnitude of the associations. The association was strongest for non-Western ethnicity (−0.28 z-score), low education (−0.19), teenage motherhood (−0.14), single motherhood (−0.13) and poverty (−0.12) and weakest for unemployment (−0.04). The deficit in fetal growth increased over time for all associations except for unemployment. Also, the measures of social adversity increasingly clustered within individuals over time. Conclusion: Maternal social disadvantage is associated with decreased fetal growth in a welfare state. Social disadvantage is increasingly clustered so that fewer pregnancies are exposed, but those exposed suffer a greater disadvantage in fetal growth. The economic upturn in the last decade did not appear to weaken the association between maternal social disadvantage and decreased fetal growth.

Advanced paternal age and mortality of offspring under 5 years of age: a register-based cohort study

STUDY QUESTION Do children born to fathers of advanced age have an increased risk of dying before the age of 5 years? SUMMARY ANSWER Children born to fathers aged 40 years or more have an increased risk of dying in early childhood due to an excess risk of fatal congenital anomalies, malignancies and external causes. WHAT IS KNOWN ALREADY Advanced paternal age has previously been associated with adverse reproductive outcomes and some long-term health problems in the offspring. This is possibly due to specific point mutations, a condition known to increase in the sperm with increasing paternal age. STUDY DESIGN, SIZE, DURATION A Danish population-based register study, designed as a prospective cohort study, of 1 575 521 live born children born from 1978 to 2004. The age of the child (in days) was used as the underlying time and the children entered the cohort the day they were born and were followed until 31 December 2009. The children were censored on date of turning 5 years, date of death or date of emigration, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS Data from population-covering registers from Statistics Denmark including the Integrated Database for Labour Market Research, the Medical Birth Registry and the Registry of Causes of Death was linked using the unique civil registry number. Hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the risk of under-five mortality. The effect of paternal age was examined using restricted cubic splines and paternal age groups. MAIN RESULTS AND THE ROLE OF CHANCE Compared with children born to fathers aged 30-34 years, a statistically significant excess risk was found for children born to fathers aged 40-44 years [HR: 1.10 (95% CI: 1.00-1.21)] and children born to fathers aged 45+ years [HR: 1.16 (95% CI: 1.02-1.32)]. When only looking at 1-5 year olds, the relative risk (HR) among children born to fathers aged 40-44 years increased to 1.24 (95% CI: 1.00-1.53) and the risk in the oldest paternal age group (45+ years) rose to 1.65 (95% CI: 1.24-2.18). The results suggest that the elevated risk for children of fathers aged 40 years or more was primarily attributed to an elevated risk of dying from congenital malformations, malignancies and external causes. LIMITATIONS, REASONS FOR CAUTION Specific causes of death might be misclassified; however, this is not likely to be dependent on paternal age. In some cases, the biological father may differ from the father registered. This misclassification is most likely non-differential. WIDER IMPLICATIONS OF THE FINDINGS The excess risk of mortality among children born to older fathers is in accordance with the literature. The association needs further attention as it can provide valuable knowledge of the etiology of genetic diseases. Also, the association could become of greater importance in the future if the proportion of fathers aged 40+ years keeps growing. STUDY FUNDING/COMPETING INTEREST (S) None.

Prenatal exposure to alcohol, and gender differences on child mental health at age seven years

Background It remains uncertain whether exposure to lower doses of alcohol is damaging to the developing fetus. The present study aimed to investigate associations for boys and girls between prenatal exposure to binge drinking and lower doses of alcohol in pregnancy, and parent-reported behavioural and emotional development at age seven. Methods This study used data from the Danish National Birth Cohort. Associations between cumulated alcohol exposure and binge drinking from full pregnancy and parent scores on the Strengths and Difficulties Questionnaire (SDQ) measured at age seven were investigated. The SDQ was used as continuous externalising/internalising scores, and as above/below cut-off for the specific scales of hyperactivity/inattention, conduct, emotional and peer problems. Inclusion criteria were information on alcohol exposure from three interviews, SDQ scores at age seven and being born full term (n=37 152). Results Controlling for relevant confounders, small positive associations were observed between binge drinking and internalising (relative change in mean: 1.04–1.06), externalising scores (relative change in mean: 1.01–1.07), and conduct scores (OR 1.12 to 1.23) for boys. No associations were observed with lower doses of alcohol. Conclusions Exposure to binge drinking is weakly associated with impaired behavioural and emotional development measured at age seven. Large differences in background characteristics were observed between the groups defined by cumulated alcohol exposure, leaving the interpretations of findings uncertain.

Prevalence of Coxiella burnetii in women exposed to livestock animals, Denmark, 1996 to 2002.

Q fever is a zoonotic infection which can pose a danger to pregnant women. To our knowledge, Denmark has never experienced a clinically verified Q fever outbreak. We aimed to quantify risk of infection in pregnant women occupationally and environmentally exposed to Coxiella burnetii. The Danish National Birth Cohort collected blood samples from 100,418 pregnant women in the period 1996 to 2002. We sampled 195 women with occupational exposure to livestock (veterinarians and female farmers), 202 women with domestic exposure (dairy cattle and/or sheep) and a random sample of 459 unexposed women. Samples were screened for antibodies against C. burnetii by commercial enzyme-linked immunosorbent assay. Positive samples were confirmed by immunofluorescence (cut-off titre ≥1:128). The proportion of seropositive women was higher in the occupationally exposed (47.2% seropositive; relative risk (RR): 9.8; 95% confidence interval (CI): 6.4–15.2) and the domestically exposed population (32.2% seropositive; RR: 6.7; 95% CI: 4.3–10.6) than in unexposed women (4.8% seropositive). We found a high prevalence of antibodies to C. burnetii among pregnant women with occupational or domestic exposure to cattle and/or sheep compared with unexposed pregnant women. Our findings suggest that contact to livestock is a risk factor for C. burnetii infection in Denmark.

International variations in the gestational age distribution of births: an ecological study in 34 high-income countries

Background Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset. Methods We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses. Results Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset. Conclusion Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.

Associations between maternal socioeconomic position and psoriasis: a cohort study among the offspring of the Danish National Birth Cohort

The socioeconomic determinants of paediatric‐onset psoriasis have not been previously investigated.

Fever in pregnancy and the risk of congenital malformations: a cohort study

BackgroundIn a variety of animal species, hyperthermia in pregnancy has been recognized as teratogenic. Hyperthermia interferes with protein synthesis via heat-shock proteins, which can entail membrane disruption, cell death, vascular disruption, and placental infarction. This can induce severe fetal malformations or death. Fever during pregnancy, especially during embryogenesis, has also been associated with congenital malformations in human offspring.The purpose of this large cohort study of clinically recognized pregnancies was to investigate whether fever during first trimester was associated with an increased risk of congenital malformations in the offspring.MethodsThe Danish National Birth Cohort is a population-based cohort of 100,418 pregnant women and their offspring recruited in 1996 to 2002. Information on fever during pregnancy was collected prospectively by means of two telephone interviews.The study population comprised the 77,344 pregnancies enrolled in the Danish National Birth Cohort where self-reported information on fever during first trimester of pregnancy was available. Pregnancy outcomes were identified through linkage with the National Patient Registry. Congenital malformations within the first three and a half years of life were categorized according to EUROCAT’s classification criteria. Logistic regression models were used to estimate the associations between fever in first trimester and overall congenital malformations and congenital malformations by subgroups.ResultsEight thousand three hundred twenty-one women reported fever during first trimester (10.8%) and 2876 infants were diagnosed with a congenital malformation (3.7%). Fever during first trimester did not affect the risk of overall fetal congenital malformation (OR 0.99, 95% CI 0.88–1.12). The subgroup analyses indicated slightly higher risk of congenital anomalies in the eye, ear, face and neck (OR 1.29, 95% CI 0.78–2.12) and in the genitals (OR 1.17, 95% CI 0.79–1.12), whereas lower risk of malformations in the nervous system (OR 0.47, 95% CI 0.21–1.08), the respiratory system (OR 0.56, 95% CI 0.23–1.29) and in the urinary subgroup (OR 0.58, 95% CI 0.35–0.99) was suggested, the latter constituting the only statistically significant finding.ConclusionsOverall, this study did not show any association between maternal fever in pregnancy and risk of congenital anomalies.

O5-6.3 Advanced paternal age and risk of death before the age of 5 years: a register-based cohort study

Introduction An association between paternal age and childrens health was suggested by Penrose as early as 1955. More recently, relationships have been suggested between paternal age and specific diseases and fetal death. The association is mainly put down to the increased mutation rate in male germ cells. The aim of this study was to investigate the relationship between paternal age and under 5-year mortality. Methods Based on data from Danish population-covering registers, we investigated the relationship between paternal age and under 5-year mortality, including cause-specific mortality, taking maternal age, parity and parental educational levels into account. A total of 1 140 689 live born children were included in the study. Cox regression models were used to estimate HRs for death during the first 5 years of life. Results Compared with children born to fathers aged 30–34 years an excess risk was found for children born to fathers aged 45+ years (HR 1.22; 95% CI 1.05 to 1.42). When only 1–5 years olds were included the RR rose to 1.70; 95% CI 1.23 to 2.34. The excess risk for children of fathers aged 45 years or more was primarily attributed to an elevated risk of dying from congenital malformations and malignancies. Conclusion Children with a father aged 45 years or more have an increased risk of dying before the age of 5 years. The findings are compatible with the hypothesis suggesting increased frequency of point mutations in the fertilising sperm cells from men of advanced age.