Katrine Strandberg-Larsen

Binge drinking in pregnancy and risk of fetal death.

OBJECTIVE: To examine whether the frequency and timing of binge drinking episodes (intake of five or more drinks on one occasion) during the first 16 weeks of pregnancy increase the risk of fetal death. METHODS: The study is based upon data from 89,201 women who were enrolled in the Danish National Birth Cohort from 1996 to 2002 and participated in an interview that took place in midpregnancy (n=86,752) or after a fetal loss (n=2,449). In total, 3,714 pregnancies resulted in fetal death. Data were analyzed by means of Cox regression models. RESULTS: Neither the frequency nor the timing of binge episodes was related to the risk of early (at or before 12 completed weeks) or late (13–21 completed weeks) spontaneous abortion. However, three or more binge episodes showed an adjusted hazard ratio of 1.56 (95% confidence interval 1.01–2.40) for stillbirth (22 or more completed weeks) relative to nonbinge drinkers. Women with an average intake of three or more drinks per week and two or more binge drinking episodes had a hazard ratio of 2.20 (95% confidence interval 1.73–2.80) compared with women with no average intake and no binge drinking. CONCLUSION: Binge drinking three or more times during pregnancy is associated with an increased risk of stillbirth, but neither frequency nor timing of binge drinking was associated with an increased risk of spontaneous abortion in clinically recognized pregnancies. LEVEL OF EVIDENCE: II

Prenatal alcohol exposure and autistic spectrum disorders - a population-based prospective study of 80 552 children and their mothers.

BACKGROUND To examine whether maternal alcohol intake, including binge drinking (intake > or =5 drinks, equivalent to 60 g pure ethanol on a single occasion), is associated with autistic spectrum disorders (ASD) and infantile autism. METHODS Participants were 80,552 children and their mothers enrolled in the Danish National Birth Cohort from 1996 to 2002. Alcohol consumption was obtained by self-report during pregnancy. Information on ASD was obtained from the Danish Central Psychiatry Register. Follow-up ended on February 2008. Data were analysed by means of Cox regression. RESULTS In total, 401 children were diagnosed with ASD and 157 with infantile autism. No association was found between average alcohol consumption and ASD or infantile autism, respectively. For binge drinking, the adjusted hazard ratio (HR) for ASD was 0.72 [95% confidence interval (CI): 0.53-0.97] among women who binge drank once during pregnancy compared with women who did not binge drink. The corresponding HR for infantile autism was 0.61 (95% CI: 0.36-1.02). However, the HR for ASD was 0.84 (95% CI: 0.51-1.36) when restricting the analysis to first-time pregnancies conceived within 6 months of trying. No estimate was made for infantile autism due to low number of cases. No association was seen for more than one binge episode and for the timing of binge drinking. CONCLUSION Our findings do not support that a low prenatal alcohol exposure increases the risk of ASD or infantile autism. The lower risk for women who binge drank once during pregnancy is most likely non-causal.

Alcohol drinking pattern during pregnancy and risk of infant mortality

Background: The safety of small amounts of alcohol drinking and occasional binge-level drinking during pregnancy remains unsettled. We examined the association of maternal average alcohol intake and binge drinking (≥5 drinks per sitting) with infant mortality, both in the neonatal and postneonatal period. Methods: Participants were 79,216 mothers who were enrolled in the Danish National Birth Cohort in 1996–2002, gave birth to a live-born singleton, and provided information while they were pregnant on alcohol consumption during pregnancy. Information on infant mortality and causes of death was obtained from national registries and medical records. Results: During the first year of life, 279 children (0.35%) died, 204 during the neonatal period. Infant mortality was not associated with alcohol drinking, even at a consumption level of either 4+ drinks per week or 3+ occasions of binge drinking. Postneonatal mortality was associated with an intake of 4+ drinks per week (hazard ratio = 3.56 [95% confidence interval = 1.15–8.43]) and with 3+ binge episodes (2.69 [1.27–5.69]). When restricting analyses to term births, both infant mortality and postneonatal mortality were associated with a weekly average intake of 4+ drinks or 3+ binge episodes. Conclusions: Among term infants, intake of at least 4 drinks of alcohol per week or binging on 3 or more occasions during pregnancy are associated with an increased risk of infant mortality, especially during the postneonatal period.

Binge Drinking During Pregnancy and Risk of Seizures in Childhood: A Study Based on the Danish National Birth Cohort

Seizures are often found in children with fetal alcohol syndrome, but it is not known whether binge drinking during pregnancy by nonalcoholic women is associated with an increased risk of seizure disorders in children. The authors conducted a population-based cohort study of 80,526 liveborn singletons in the Danish National Birth Cohort (1996-2002). Information on maternal binge drinking (intake of > or = 5 drinks on a single occasion) was collected in 2 computer-assisted telephone interviews during pregnancy. Children were followed for up to 8 years. Information on neonatal seizures, epilepsy, and febrile seizures was retrieved from the Danish National Hospital Register. Results showed that exposure to binge drinking episodes during pregnancy was not associated with an increased risk of seizure disorders in children, except for those exposed at 11-16 gestational weeks. These children had a 3.15-fold increased risk of neonatal seizures (95% confidence interval: 1.37, 7.25) and a 1.81-fold increased risk of epilepsy (95% confidence interval: 1.13, 2.90). These findings suggest that maternal binge drinking during a specific time period of pregnancy may be associated with an increased risk of specific seizure disorders in the offspring. The results are exploratory, however, and need to be replicated.

Influence of the recall period on a beverage-specific weekly drinking measure for alcohol intake

Background/Objectives:Our knowledge of the association between alcohol intake and alcohol-related health outcomes depends, to a large extent, on the validity and reliability of self-reported alcohol intake. Weekly drinking measures are frequently used in epidemiological surveys, but it has been shown that respondents have problems in correctly reporting intake for a full week. The aim of this study is to investigate whether a beverage-specific question implies better recall and, thereby, eliminates or diminishes the previously reported association between the recall period and the self-reported weekly alcohol intake.Subjects/Methods:The data is derived from the Danish Health Interview Survey 2005, which is based on a region-stratified random sample of 21 832 Danish citizens aged ≥16 years (response rate: 67%). The data were collected via face-to-face interviews.Results:A beverage-specific question on alcohol intake on each day during the last week did not alter the strong association between the recall period and self-reported alcohol intake. However, the overall self-reported alcohol intake increased substantially when using the beverage-specific question instead of asking for the overall alcohol intake on each day. Moreover, the analyses indicated that interviews on Sundays should be avoided if the purpose is to assess alcohol intake for the previous day (Saturdays).Conclusions:It seems problematic to recall alcohol intake even when the recall period is as short as 1 week. Weekly drinking measures should primarily be used when the main aim of the study is to assess the average volume of alcohol intake in a specific population.

Use of ADHD medication during pregnancy from 1999 to 2010: a Danish register‐based study

This study aimed to describe the trends in use of Attention Deficit Hyperactivity Disorders (ADHD) medication during pregnancy in Denmark from 1999 to 2010, as well as to explore characteristics of women who use ADHD medication during pregnancy and whether exposure is associated with outcome of pregnancy.

Do women give the same information on binge drinking during pregnancy when asked repeatedly

Objective:To study if pregnant women give the same answers to questions on frequency and timing of binge drinking when asked more than once during and after pregnancy.Design:Cohort study.Setting:The Danish National Birth Cohort.Subjects:The study is based on 76 307 pregnant women with repeated information on binge drinking during the early part of pregnancy and 8933 pregnant women with information on binge drinking during pregnancy weeks 30–36, obtained while pregnant and 6 months after delivery.Results:More women reported binge drinking, if the interview took place close to the period in question. As the report of binge drinking was highest in the first of two interviews referring to the same period, as well as women who participated in the first interview in pregnancy week 12 or earlier reported more binge drinking compared to women who participated in the interview later in pregnancy.Conclusions:Self-reported information on binge drinking is more frequently under-reported when the recall period is long. To improve the validity of data on binge drinking, future birth cohorts should obtain information several times during pregnancy.Sponsorship:The Danish National Board of Health and the Health Insurance Foundation.

Maternal Use of Selective Serotonin Reuptake Inhibitors and Risk of Miscarriage – Assessing Potential Biases

BACKGROUND The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with miscarriage, but the association may be biased by maternal mental illness, lifestyle and exposure misclassification. METHODS A register study on all pregnancies in Denmark between 1996 and 2009 was conducted using individualised data from the Danish National Patient Register, the Medical Birth Register, the Danish Psychiatric Central Register, the Danish National Prescription database and the Danish National Birth Cohort (DNBC). RESULTS A total of 1 191164 pregnancies were included in the study, of which 98275 also participated in the DNBC. Pregnancies exposed to SSRIs during or before pregnancy were more likely than unexposed pregnancies to result in first trimester miscarriage, hazard rate (HR)=1.08 [95% confidence interval (CI) 1.04, 1.13] and HR=1.26 [95% CI 1.16, 1.37], respectively. No difference was observed for second trimester miscarriage. SSRI-exposed pregnancies without a maternal depression/anxiety diagnosis from a psychiatric department were less likely to result in first trimester miscarriage than unexposed pregnancies with a diagnosis, HR=0.85 [95% CI 0.76, 0.95]. SSRI-exposed pregnancies were characterised by an unhealthier maternal lifestyle and mental health profile than unexposed pregnancies, whereas no convincing differences were observed between pregnancies exposed to SSRIs during versus before pregnancy. Substantial disagreement was found between prescriptions and self-reported use of SSRIs, but it did not affect the estimated hazard ratios. CONCLUSION Confounding by indication and lifestyle in pregnancy may explain the association between SSRI use and miscarriage.

Exploring Educational Disparities in Risk of Preterm Delivery: A Comparative Study of 12 European Birth Cohorts

BACKGROUND An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. METHODS The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. CONCLUSIONS Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.

Self-reported stress and risk of endometrial cancer: a prospective cohort study

Objectives: To assess a possible relationship between perceived stress and first-time incidence of primary endometrial cancer. Psychological stress may affect the synthesis and metabolism of estrogens and thereby be related to risk of endometrial cancer. Methods: The 6760 women participating in the Copenhagen City Heart Study were asked about their stress level at baseline from 1981 to 1983. These women were prospectively followed up in the Danish nationwide cancer registry until 2000 and <0.1% were lost to follow-up. Cox proportional hazard models were used to analyze data. Results: During follow-up, 72 women were diagnosed with endometrial cancer. For each increase in stress level on a 7-point stress scale, there was a lower risk of primary endometrial cancer (hazard ratio (HR) = 0.88; 95% confidence interval (CI), 0.76–1.01). This inverse association was particularly strong in women who received hormone therapy (HR = 0.77; 95% CI, 0.61–0.96) and in normal-weight women (HR = 0.73; 95% CI, 0.58–0.91). Conclusions: Stress may affect gonadal synthesis of estrogens and alter the sensitivity of the uterus toward estrogen stimulation. These mechanisms may explain the lower risk of endometrial cancer observed among stressed women in this study. Despite these results, stress may still be a risk factor for a range of other diseases and should therefore not be considered a healthy response. HR = hazard ratio; CI = confidence interval; HPG = hypothalamic-pituitary-gonadal; HPA = hypothalamic-pituitary-adrenal; BMI = body mass index