Producing valid statistics when legislation, culture, and medical practices differ for births at or before the threshold of survival: Report of a European workshop

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Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries

Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

Objective Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. Study Design We conducted a nested case-control study within the Norwegian Mother, Father and Child Birth Cohort (1999-2008) of 2,596 mother-child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. Results Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). Conclusion Evidence for gene-smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene-environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. Key Points Maternal and fetal genotype may differentially influence preeclampsia. Smoking-related genes did not strongly modify smoking-preeclampsia association. Smoking cessation reduced strength of gene by smoking interactions

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Abstract Introduction Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. Methods We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Results Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, antiasthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. A presentation was given at the 54th Annual Meeting of the Teratology Society in Washington, USA, 28 June-2 July 2014. Key Points Linkage of primary care or prescription databases to congenital anomaly (CA) registries improved the quality of information on maternal use of medicines in pregnancy. The quality of information improved particularly for medicine groups that are less fully registered in CA registries, such as selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants

Risk factors for mortality in infancy and childhood in children with major congenital anomalies: a European population-based cohort study

BACKGROUND: Preterm birth and young maternal age are known risk factors for infant and childhood mortality. There is limited knowledge of the impact of these risk factors in children born with major congenital anomalies (CAs), who have inherently higher risks of death compared with other children.OBJECTIVES: To investigate the risk factors for mortality up to age 10 years in children born with specific major CAs.METHODS: This population-based cohort study involved 150,198 livebirths from 1995 to 2014 in 13 European CA registries linked to mortality data. Cox proportional hazards models estimated the association of gestational age, maternal age and child's sex with death &lt;1 year and 1-9 years for the whole cohort and by CA subgroup. Hazard ratios (HR) from each registry were pooled using multivariate meta-analysis.RESULTS: Preterm birth had a dose-response association with mortality; compared with infants born at 37+ weeks gestation, those born at &lt;28, 28-31 and 32-36 weeks had 14.88 (95% CI 12.57, 17.62), 8.39 (95% CI 7.16, 9.85) and 3.88 (95% CI 3.40, 4.43) times higher risk of death &lt;1 year, respectively. The corresponding risks at 1-9 years were 4.99 (95% CI 2.94, 8.48), 3.09 (95% CI 2.28, 4.18) and 2.04 (95% CI 1.69, 2.46) times higher, respectively. Maternal age &lt;20 years (versus 20-34 years) was a risk factor for death &lt;1 year (HR 1.30, 95% CI 1.09, 1.54) and 1-9 years (HR 1.58, 95% CI 1.19, 2.10). Females had 1.22 (95% CI: 1.07, 1.39) times higher risk of death between 1 and 9 years than males.CONCLUSION: Preterm birth was associated with considerably higher infant and childhood mortality in children with CAs, comparable to estimates reported elsewhere for the background population. Additional risk factors included young maternal age and female sex. Information on risk factors could benefit clinical care and guide counselling of parents following CA diagnoses.</p

Factors associated with non-attendance, opportunistic attendance and reminded attendance to cervical screening in an organized screening program: a cross-sectional study of 12,058 Norwegian women

<p>Abstract</p> <p>Background</p> <p>Cervical cancer incidence and mortality may be reduced by organized screening. Participant compliance with the attendance recommendations of the screening program is necessary to achieve this. Knowledge about the predictors of compliance is needed in order to enhance screening attendance.</p> <p>Methods</p> <p>The Norwegian Co-ordinated Cervical Cancer Screening Program (NCCSP) registers all cervix cytology diagnoses in Norway and individually reminds women who have no registered smear for the past three years to make an appointment for screening. In the present study, a questionnaire on lifestyle and health was administered to a random sample of Norwegian women. The response rate was 68%. To address the predictors of screening attendance for the 12,058 women aged 25-45 who were eligible for this study, individual questionnaire data was linked to the cytology registry of the NCCSP. We distinguished between non-attendees, opportunistic attendees and reminded attendees to screening for a period of four years. Predictors of non-attendance versus attendance and reminded versus opportunistic attendance were established by multivariate logistic regression.</p> <p>Results</p> <p>Women who attended screening were more likely than non-attendees to report that they were aware of the recommended screening interval, a history of sexually transmitted infections and a history of hormonal contraceptive and condom use. Attendance was also positively associated with being married/cohabiting, being a non-smoker and giving birth. Women who attended after being reminded were more likely than opportunistic attendees to be aware of cervical cancer and the recommended screening interval, but less likely to report a history of sexually transmitted infections and hormonal contraceptive use. Moreover, the likelihood of reminded attendance increased with age. Educational level did not significantly affect the women's attendance status in the fully adjusted models.</p> <p>Conclusions</p> <p>The likelihood of attendance in an organized screening program was higher among women who were aware of cervical screening, which suggests a potential for a higher attendance rate through improving the public knowledge of screening. Further, the lower awareness among opportunistic than reminded attendees suggests that physicians may inform their patients better when smears are taken at the physician's initiative.</p

Modifiable risk factors predicting major depressive disorder at four year follow-up: a decision tree approach

<p>Abstract</p> <p>Background</p> <p>Relative to physical health conditions such as cardiovascular disease, little is known about risk factors that predict the prevalence of depression. The present study investigates the expected effects of a reduction of these risks over time, using the decision tree method favoured in assessing cardiovascular disease risk.</p> <p>Methods</p> <p>The PATH through Life cohort was used for the study, comprising 2,105 20-24 year olds, 2,323 40-44 year olds and 2,177 60-64 year olds sampled from the community in the Canberra region, Australia. A decision tree methodology was used to predict the presence of major depressive disorder after four years of follow-up. The decision tree was compared with a logistic regression analysis using ROC curves.</p> <p>Results</p> <p>The decision tree was found to distinguish and delineate a wide range of risk profiles. Previous depressive symptoms were most highly predictive of depression after four years, however, modifiable risk factors such as substance use and employment status played significant roles in assessing the risk of depression. The decision tree was found to have better sensitivity and specificity than a logistic regression using identical predictors.</p> <p>Conclusion</p> <p>The decision tree method was useful in assessing the risk of major depressive disorder over four years. Application of the model to the development of a predictive tool for tailored interventions is discussed.</p

Maternal risk factors for the VACTERL association: a EUROCAT case-control study

International audienc

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors