Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Interpregnancy weight change and recurrence of gestational diabetes mellitus: a population-based cohort study.

OBJECTIVE: To estimate recurrence risk of gestational diabetes mellitus (GDM) by interpregnancy weight change. DESIGN: Population-based cohort study. SETTING AND POPULATION: Data from the Swedish (1992-2010) and the Norwegian (2006-2014) Medical Birth Registries on 2763 women with GDM in first pregnancy, registered with their first two singleton births and available information on height and weight. METHODS: Interpregnancy weight change (BMI in second pregnancy minus BMI in first pregnancy) was categorised in six groups by BMI units. Relative risks (RRs) of GDM recurrence were obtained by general linear models for the binary family and adjusted for confounders. Analyses were stratified by BMI in first pregnancy (<25 and ≥25 kg/m2 ). MAIN OUTCOME MEASURE: GDM in second pregnancy. RESULTS: Among overweight/obese women (BMI ≥25), recurrence risk of GDM decreased in women who reduced their BMI by 1-2 units (relative risk [RR] 0.80, 95% CI 0.65-0.99) and >2 units (RR 0.72, 95% CI 0.59-0.89) and increased if BMI increased by ≥4 units (RR 1.26, 95% CI 1.05-1.51) compared wth women with stable BMI (-1 to 1 units). In normal weight women (BMI <25), risk of GDM recurrence increased if BMI increased by 2-4 units (RR 1.32, 95% CI 1.08-1.60) and ≥4 units (RR 1.61, 95% CI 1.28-2.02) compared with women with stable BMI. CONCLUSION: Interpregnancy weight loss reduced risk of GDM recurrence in overweight/obese women. Weight gain between pregnancies increased recurrence risk for GDM in both normal and overweight/obese women. Our findings highlight the importance of weight management in the interconception window in women with a history of GDM. TWEETABLE ABSTRACT: Interpregnancy weight loss reduces recurrence of gestational diabetes mellitus in overweight/obese women.

Gender differences in psychiatric comorbidity: a population-based study of 40 000 adults with attention deficit hyperactivity disorder.

OBJECTIVE: We aimed at determining whether gender modified associations between ADHD and psychiatric comorbidities in adults. METHOD: We identified adults with ADHD by linking Norwegian national registries and compared them with the remaining adult population (born 1967-1997, ADHD and bipolar during 2004-2015, other psychiatric disorders 2008-2015). Prevalence differences (PDs) and prevalence ratios (PRs) of psychiatric disorders were determined by Poisson regression. Interaction by gender was evaluated on additive (PDs) and multiplicative (PRs) scales. Proportions of psychiatric disorders attributable to ADHD were calculated. RESULTS: We identified 40 103 adults with ADHD (44% women) and 1 661 103 adults (49% women) in the remaining population. PDs associated with ADHD were significantly larger in women than in men for anxiety, depression, bipolar and personality disorders, for example depression in women: 24.4 (95% CI, 23.8-24.9) vs. in men: 13.1 (12.8-13.4). PDs were significantly larger in men for schizophrenia and substance use disorder (SUD), for example SUD in men: 23.0 (22.5-23.5) vs. in women: 13.7 (13.3-14.0). Between 5.6 and 16.5% of psychiatric disorders in the population were attributable to ADHD. CONCLUSION: The association between ADHD and psychiatric comorbidities differed significantly among men and women. Clinicians treating adults with ADHD should be aware of these frequent and gender-specific comorbidities, such that early treatment can be offered.

The limitations of some European healthcare databases for monitoring the effectiveness of pregnancy prevention programmes as risk minimisation measures.

PURPOSE: Pregnancy prevention programmes (PPPs) exist for some medicines known to be highly teratogenic. It is increasingly recognised that the impact of these risk minimisation measures requires periodic evaluation. This study aimed to assess the extent to which some of the data needed to monitor the effectiveness of PPPs may be present in European healthcare databases. METHODS: An inventory was completed for databases contributing to EUROmediCAT capturing pregnancy and prescription data in Denmark, Norway, the Netherlands, Italy (Tuscany/Emilia Romagna), Wales and the rest of the UK, to determine the extent of data collected that could be used to evaluate the impact of PPPs. RESULTS: Data availability varied between databases. All databases could be used to identify the frequency and duration of prescriptions to women of childbearing age from primary care, but there were specific issues with availability of data from secondary care and private care. To estimate the frequency of exposed pregnancies, all databases could be linked to pregnancy data, but the accuracy of timing of the start of pregnancy was variable, and data on pregnancies ending in induced abortions were often not available. Data availability on contraception to estimate compliance with contraception requirements was variable and no data were available on pregnancy tests. CONCLUSION: Current electronic healthcare databases do not contain all the data necessary to fully monitor the effectiveness of PPP implementation, and thus, special data collection measures need to be instituted.

Gestational diabetes mellitus and interpregnancy weight change: A population-based cohort study.

BACKGROUND: Being overweight is an important risk factor for Gestational Diabetes Mellitus (GDM), but the underlying mechanisms are not understood. Weight change between pregnancies has been suggested to be an independent mechanism behind GDM. We assessed the risk for GDM in second pregnancy by change in Body Mass Index (BMI) from first to second pregnancy and whether BMI and gestational weight gain modified the risk. METHODS AND FINDINGS: In this observational cohort, we included 24,198 mothers and their 2 first pregnancies in data from the Medical Birth Registry of Norway (2006-2014). Weight change, defined as prepregnant BMI in second pregnancy minus prepregnant BMI in first pregnancy, was divided into 6 categories by units BMI (kilo/square meter). Relative risk (RR) estimates were obtained by general linear models for the binary family and adjusted for maternal age at second delivery, country of birth, education, smoking in pregnancy, interpregnancy interval, and year of second birth. Analyses were stratified by BMI (first pregnancy) and gestational weight gain (second pregnancy). Compared to women with stable BMI (-1 to 1), women who gained weight between pregnancies had higher risk of GDM-gaining 1 to 2 units: adjusted RR 2.0 (95% CI 1.5 to 2.7), 2 to 4 units: RR 2.6 (2.0 to 3.5), and ≥4 units: RR 5.4 (4.0 to 7.4). Risk increased significantly both for women with BMI below and above 25 at first pregnancy, although it increased more for the former group. A limitation in our study was the limited data on BMI in 2 pregnancies. CONCLUSIONS: The risk of GDM increased with increasing weight gain from first to second pregnancy, and more strongly among women with BMI < 25 in first pregnancy. Our results suggest weight change as a metabolic mechanism behind the increased risk of GDM, thus weight change should be acknowledged as an independent factor for screening GDM in clinical guidelines. Promoting healthy weight from preconception through the postpartum period should be a target.

Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study.

OBJECTIVE: To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies. DESIGN: Meta-analysis of aggregated data from three cohort studies. SETTING: Linkage between healthcare databases and EUROCAT congenital anomaly registries. POPULATION: 519 242 pregnancies in Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010). METHODS: Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses. MAIN OUTCOME MEASURES: ORs for all congenital anomalies and specific congenital anomalies. RESULTS: Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09-1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposed to inhaled corticosteroids (3.40; 99% CI 1.15-10.04). For severe congenital heart defects, an increased OR (1.97; 1.12-3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20-4.67). CONCLUSION: The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations with combination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken. TWEETABLE ABSTRACT: This cohort study found a small increased risk of congenital anomalies for women taking asthma medication.

Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries.

OBJECTIVE: The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic countries. DESIGN: Population-based cohort study. SETTING AND POPULATION: A 3-year Nordic collaboration among obstetricians to identify and report on uterine rupture, peripartum hysterectomy, excessive blood loss, and AIP from 2009 to 2012 The Nordic Obstetric Surveillance Study (NOSS). METHODS: In the NOSS study, clinicians reported AIP cases from maternity wards and the data were validated against National health registries. MAIN OUTCOME MEASURES: Prevalence, risk factors, antenatal suspicion, birth complications, and risk estimations using aggregated national data. RESULTS: A total of 205 cases of AIP in association with laparotomy were identified, representing 3.4 per 10 000 deliveries. The single most important risk factor, which was reported in 49% of all cases of AIP, was placenta praevia. The risk of AIP increased seven-fold after one prior caesarean section (CS) to 56-fold after three or more CS. Prior postpartum haemorrhage was associated with six-fold increased risk of AIP (95% confidence interval 3.7-10.9). Approximately 70% of all cases were not diagnosed antepartum. Of these, 39% had prior CS and 33% had placenta praevia. CONCLUSION: Our findings indicate that a lower CS rate in the population may be the most effective way to lower the incidence of AIP. Focused ultrasound assessment of women at high risk will likely strengthen antenatal suspicion. Prior PPH is a novel risk factor associated with an increased prevalence of AIP. TWEETABLE ABSTRACT: An ultrasound assessment in women with placenta praevia or prior CS may double the awareness for AIP.

Pre-pregnant body mass index and recreational physical activity: effects on perinatal mortality in a prospective pregnancy cohort.

OBJECTIVE: To examine the effect of maternal pre-pregnant body mass index (BMI) and recreational physical activity on perinatal mortality. DESIGN: A prospective cohort study. SETTING: The Norwegian Mother and Child Cohort (MoBa), 1999-2008. POPULATION: Singleton pregnancies without congenital anomalies (n = 77 246). METHODS: Pre-pregnant BMI was classified as underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), obese (30-34.9) or morbidly obese (BMI ≥ 35). Risk estimates were obtained by logistic regression and adjusted for confounders. MAIN OUTCOME MEASURES: Perinatal death (stillbirth ≥ 22 weeks plus early neonatal death 0-7 days after birth). RESULTS: An increased risk of perinatal death was seen in obese [odds ratio (OR) 2.4, 95% CI (confidence interval) 1.7-3.4] and morbidly obese women (OR 3.3, 95% CI 2.1-5.1) as compared with normal weight women. In the group participating in recreational physical activity during pregnancy, obese women had an OR of 3.2 (95% CI 2.2-4.7) for perinatal death relative to non-obese women. In the non-active group the corresponding OR was 1.8 (95% CI 1.1-2.8) for obese women compared with non-obese women. The difference in perinatal mortality risk related to obesity between the active and non-active groups was statistically significant (P-value for interaction = 0.046, multiplicative model). CONCLUSIONS: Maternal obesity was associated with a two- to three-fold increased risk of perinatal death when compared with normal weight. For women with a BMI <30 the lowest perinatal mortality was seen in those performing recreational physical activity at least once a week.

Pre-eclampsia and assisted reproductive technologies: consequences of advanced maternal age, interbirth intervals, new partner and smoking habits.

OBJECTIVE: To examine the risk of pre-eclampsia (PE) in women conceiving after assisted reproductive technologies (ART). Potential confounding from maternal age, long intervals between births, new partner and smoking were evaluated. DESIGN AND SETTING: Population-based cohort study with data from the Medical Birth Registry of Norway. POPULATION: A total of 501,766 mothers with offspring from 1988 to 2009. METHODS: Births to the same mother were linked in sibship data files with information of ART. MAIN OUTCOME MEASURES: Odds ratio (OR) (95% confidence intervals) of PE in pregnancies conceived by ART compared with spontaneous conception, stratified by parity. RESULTS: The prevalence of PE was 5.1% in first, 2.2% in second and 2.1% in third pregnancies. Corresponding figures in ART pregnancies were 6.0%, 3.3% and 4.4%. Hence, the odds ratios of PE in ART pregnancies relative to spontaneous pregnancies increased from 1.2 (1.1-1.3) in first, 1.5 (1.3-1.8) in second to 2.1 (1.4-3.3) in third pregnancies. Adjusting by maternal age lowered the odds ratio to 1.3 (1.1-1.6) and 1.8 (1.2-2.8) in second and third pregnancies, respectively. Multi-adjusted, birth interval had more impact than change of partner. Smoking was associated with a strongly reduced PE risk (odds ratio 0.65; 0.62-0.69), but there was no confounding by smoking on the ART associated risk. CONCLUSIONS: Assisted reproductive technologies increases the risk of PE, and the risk may increase by parity. The association between ART pregnancies and PE is to some extent explained by interbirth intervals and advanced maternal age, but not to change of partner or smoking.

Maternal age and emergency operative deliveries at term: a population-based registry study among low-risk primiparous women.

OBJECTIVE: To study the association between maternal age and emergency operative delivery. The roles of in-labour indications, and birthweight ≥ 4000 g, gestational age ≥ 42 weeks, induction of labour, and epidural use, according to maternal age were explored. DESIGN: Population-based study. SETTING: Medical Birth Registry of Norway and Statistics Norway. POPULATION: We studied 169 583 low-risk primiparous mothers with singleton, cephalic labours, at ≥37 weeks of gestation, from 1999 to 2009. METHODS: The associations between maternal age and mode of delivery were analysed using multinomial regression analyses, adjusting for sociodemographic factors. MAIN OUTCOME MEASURES: Emergency caesarean section and operative vaginal delivery. RESULTS: Of women aged ≥40 years, 22% had emergency caesarean sections and 24% had operative vaginal deliveries, giving adjusted relative risk ratios (RRRs) of 6.60 (95% confidence interval, 95% CI 5.53-7.87) and 3.30 (95% CI 2.79-3.90), respectively, when compared with women aged 20-24 years. Adjustments for sociodemographic factors only slightly changed the estimates. Dystocia was the main indication, followed by fetal distress. All of the listed factors increased the level of emergency operative deliveries, mainly because of an increase in dystocia. The increase in risk for emergency caesarean section by all factors, and for operative vaginal deliveries by epidural, were greater in older than in younger women, but were significant for epidural only. CONCLUSIONS: We found a close association between maternal age and emergency operative delivery in low-risk primiparas. Contributory factors increased the risk for both emergency operative delivery and epidural more in older than in younger women.

Availability and access in modern obstetric care: a retrospective population-based study.

OBJECTIVE: To assess the availability of obstetric institutions, the risk of unplanned delivery outside an institution and maternal morbidity in a national setting in which the number of institutions declined from 95 to 51 during 30 years. DESIGN: Retrospective population-based, three cohorts and two cross-sectional analyses. SETTING: Census data, Statistics Norway. The Medical Birth Registry of Norway from 1979 to 2009. POPULATION: Women (15-49 years), 2000 (n = 1,050,269) and 2010 (n = 1,127,665). Women who delivered during the period 1979-2009 (n = 1,807,714). METHODS: Geographic Information Systems software for travel zone calculations. Cross-table and multiple logistic regression analysis of change over time and regional differences. World Health Organization Emergency Obstetric and Newborn Care (EmOC) indicators. MAIN OUTCOME MEASURES: Proportion of women living outside the 1-hour travel zone to obstetric institutions. Risk of unplanned delivery outside obstetric institutions. Maternal morbidity. RESULTS: The proportion of women living outside the 1-hour zone for all obstetric institutions increased from 7.9% to 8.8% from 2000 to 2010 (relative risk, 1.1; 95% confidence interval, 1.11-1.12), and for emergency obstetric care from 11.0% to 12.1% (relative risk, 1.1; 95% confidence interval, 1.09-1.11). The risk of unplanned delivery outside institutions increased from 0.4% in 1979-83 to 0.7% in 2004-09 (adjusted odds ratio, 2.0; 95% confidence interval, 1.9-2.2). Maternal morbidity increased from 1.7% in 2000 to 2.2% in 2009 (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.5) and the regional differences increased. CONCLUSIONS: The availability of and access to obstetric institutions was reduced and we did not observe the expected decrease in maternal morbidity following the centralisation.

Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007.

OBJECTIVE: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. DESIGN: Descriptive epidemiological analysis of data from population-based congenital anomaly registries. SETTING: Fourteen European countries. POPULATION: A total of 5.4 million births 1984-2007, of which 3% were multiple births. METHODS: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. MAIN OUTCOME MEASURES: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. RESULTS: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. CONCLUSIONS: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.