Helle Larsen

Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study

Abstract Objective: To estimate the risk of adverse birth outcome in women who take non-steroidal anti-inflammatory drugs during pregnancy. Design and setting: Population based cohort study and a case-control study, both based on data from a prescription registry, the Danish birth registry, and one countys hospital discharge registry. Participants: Cohort study: 1462 pregnant women who had taken up prescriptions for non-steroidal anti-inflammatory drugs in the period from 30 days before conception to birth and 17 259 pregnant women who were not prescribed any drugs during pregnancy. Case-control study: 4268 women who had miscarriages, of whom 63 had taken non-steroidal anti-inflammatory drugs, and 29 750 primiparous controls who had live births. Main outcome measures: Incidences of congenital abnormality, low birth weight, preterm birth, and miscarriage. Results: Odds ratios for congenital abnormality, low birth weight, and preterm birth among women who took up prescriptions for non-steroidal anti-inflammatory drugs were 1.27 (95% confidence interval 0.93 to 1.75), 0.79 (0.45 to 1.38), and 1.05 (0.80 to 1.39) respectively. Odds ratios for the taking up of prescriptions in the weeks before miscarriage ranged from 6.99 (2.75 to 17.74) when prescriptions were taken up during the last week before the miscarriage to 2.69 (1.81 to 4.00) when taken up between 7 and 9 weeks before. The risk estimates were no different when the analysis was restricted to missed abortions. Conclusions: Use of non-steroidal anti-inflammatory drugs during pregnancy does not seem to increase the risk of adverse birth outcome but is associated with increased risk of miscarriage.

Predictive value and completeness of the registration of congenital abnormalities in three Danish population-based registries

Aims: The predictive value and completeness of data on congenital abnormalities (CAs) collected in three administrative health registries in the County of North Jutland, Denmark were compared. Methods: The study included all singleton liveborn infants in the county during the period 1991—94 (n=24,147). All infants recorded as having a CA in either the Medical Birth Registry (MBR), the Hospital Discharge Registry (HDR), or the National Registry of Congenital Abnormalities (NRCA) were identified, and the recordings in each registry were compared. Infants recorded in at least two registries were considered correctly diagnosed with a CA for the sake of the analyses. The predictive value was defined as the number of infants correctly diagnosed with a CA in the registry divided by the total number of infants recorded with a CA in the registry. In all cases with recording in one registry only, the predictive value of the registration with CA diagnosis was assessed through a review of a sample of medical records. The completeness was defined as the number of correctly diagnosed CAs in the registry divided by the total number of identified CAs. Results: The predictive value and completeness were calculated as 89.1% (85.3—92.8) and 32.3% (28.9—35.7) in the MBR; 88.2% (85.9—90.5) and 89.9% (87.7—92.1) in the HDR; and 99.6% (98.9—100.0) and 36.0% (32.5—39.5) in the NRCA. Conclusions: The HDR seems to have a predictive value and completeness that are acceptable for general surveillance and epidemiological research regarding CAs. The NRCA may be suitable for case-control studies owing to a high predictive value.

Psychomotor development in children exposed in utero to benzodiazepines, antidepressants, neuroleptics, and anti-epileptics

We did a follow-up study based upon a regional prescription register in Denmark. We identified all 435 women who in the period 1991–1996 had redeemed a prescription for CNS drugs during pregnancy. Among the rest of the pregnant women we randomly selected 1304 women who also had given birth to a child in the same region and period. We looked up the local health nurses Boel test results which were available for about 80%. Any abnormal test result was seen much more frequently among exposed (16%) than for not exposed (4%). The study has several limitations but raises concern that should be addressed in other and better designed studies.

Birth outcome following maternal use of fluoroquinolones

The aim of the study was to examine fetal risk associated with intrauterine exposure to fluoroquinolones. By using on record linkage between a Prescription Database and the Birth Registry in Denmark, the offspring of 57 users of fluoroquinolones and of 17259 patients who had no prescriptive medication during pregnancy, were compared in a cohort study. Among the users, the prevalence rate ratios of congenital abnormalities, preterm birth and low birth weight were 1.30 (95% CI: 0.30-5.30),1.53 (95% CI: 0.62-3.80) and 1.17 (95% CI: 0.15-8.90), respectively. The risk of congenital abnormalities among users of fluoroquinolones during pregnancy was close to unity. Despite these limitations of statistical analysis the study suggested that the use of fluoroquinolones during pregnancy may not be a major risk factor to the foetus.

ABO blood groups and risk of venous thromboembolism during pregnancy and the puerperium. A population‐based, nested case–control study

Summary.  Objectives: To examine possible associations of ABO blood types with the risk of venous thromboembolism (VTE) in pregnancy and the puerperium. Patients and methods: We conducted a nested case–control study within a cohort of 71 729 women who gave birth to 126 783 children in the North Jutland County, Denmark, from 1980 to 2001. We identified 129 cases with VTE in pregnancy (n = 61) or the puerperium (n = 68), and 258 controls with no VTE. We collected information on ABO blood groups and possible maternal confounding factors and estimated the relative risk [odds ratio (OR)]. Results: Women with an A or AB blood group had elevated risk estimates of VTE in pregnancy or the puerperium compared with women with a O blood group [adjusted ORs 2.4, 95% confidence interval (CI) 1.3, 4.3, and 2.0, 95% CI 0.7, 5.8, respectively]. No increased risk estimate was found for group B (adjusted OR 1.2, 95% CI 0.5, 3.0). The increased risk estimates of VTE for blood groups A and AB appeared present in both pregnancy (adjusted ORs of 3.9, 95% CI 1.5, 9.7, and 2.2, 95% CI 0.4, 12.5) and in the puerperium (adjusted ORs of 2.4, 95% CI 1.0, 4.9 and 2.7, 95% CI 0.8, 9.3). Furthermore, blood groups A and AB appeared to be associated with increased risk estimates for both DVT and pulmonary embolism. Conclusion: Keeping the modest statistical precision of our study in mind, blood groups A and AB may be associated with increased risk estimates for VTE in pregnancy and the puerperium.

Risk of Infantile Hypertrophic Pyloric Stenosis after Maternal Postnatal Use of Macrolides

A case report has suggested that exposure to erythromycin through breast milk might cause infantile hypertrophic pyloric stenosis. This study therefore examined whether macrolides, transmitted via breast milk, increase the risk of infantile hypertrophic pyloric stenosis in neonates. A population-based cohort study was conducted, based on data from a prescription registry, the Danish Birth Registry and North Jutland Countys hospital discharge registry, Denmark, and comprising 1166 pregnant women who had been prescribed macrolides from birth to 90 d postnatally, and 34,690–41,778 pregnant women as controls. The odds ratios for infantile hypertrophic pyloric stenosis varied between 2.3 and 3.0 according to different periods of postnatal exposure, and after stratification for gender they were 10.3 [95% confidence interval (95% CI) 1.2–92.3] for girls and 2.0 (95% CI 0.5–8.4) for boys. The use of macrolides during breast-feeding increases the risk of infantile hypertrophic pyloric stenosis.

Smoking, sex of the offspring, and risk of placental abruption, placenta previa, and preeclampsia: a population-based cohort study

Background. Placental abruption, placenta previa, and preeclampsia are serious pregnancy complications with an increased risk of perinatal death. Smoking during pregnancy is associated with increased risk of abruption and placenta previa, and it reduces the risk of preeclampsia. We examined the association between mothers’ smoking habits during pregnancy, taking the sex of the offspring into consideration, and the risk and prognosis of placental abruption, placenta previa, and preeclampsia

Birth outcomes in women exposed to anticonvulsant drugs

Objectives– To examine the risk of malformations and fetal growth in women treated with anticonvulsant drugs in North Jutland County, Denmark. Material and methods– All women treated with anti‐convulsant drugs in the county were identified in a Pharmaco‐Epidemiological Prescription Database and linked to the Danish Medical Birth Registry and the Regional Hospital Discharge Registry. Results– We identified 235 pregnancies exposed to anticonvulsants around conception and/or during pregnancy as well as 17,259 unexposed pregnancies where the mother had not received any prescription. There was 1 case of neural tube defect among 15 malformations in the exposed cohort. The overall risk of malformations was 2.2 (95% confidence intervals 1.3–3.8). The risk of low birth weight and preterm delivery was 1.5 (95% confidence intervals 0.6–3.7) and 1.6 (95% confidence intervals 1.0–2.5), respectively. Conclusion– We found an increased risk of congenital malformations and a tendency to growth retardation in children of women exposed to anticonvulsants.

Maternal smoking and risk of hypertrophic infantile pyloric stenosis: 10 year population based cohort study

Infantile hypertrophic pyloric stenosis affects 0.5 to 3.0 per 1000 live births. 1 2 The aetiology is unclear, but family history and sex distribution seem important and might indicate a genetic role.3 However, a recently reported fall in the incidence of infantile hypertrophic pyloric stenosis suggests that environmental factors are also important.4 During the last decade a similar reduction in the proportion of pregnant women who smoke was reported in Denmark,5 raising the possibility that maternal smoking is a risk factor for infantile hypertrophic pyloric stenosis. This hypothesis is supported by the reported ecological association between infantile hypertrophic pyloric stenosis and sudden infant death syndrome.1 Maternal smoking is also a risk factor for sudden infant death syndrome,1 and we therefore examined whether maternal smoking was a …

Influence of chorionicity on perinatal outcome in a large cohort of Danish twin pregnancies.

To assess outcome in twin pregnancies according to chorionicity.