Kari Klungsøyr Melve

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7–22.4) for trisomy 21, 5.0 (95% CI 4.8–5.1) for trisomy 18 and 2.0 (95% CI 1.9–2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9–11.5) for trisomy 21, 1.04 (95% CI 0.96–1.12) for trisomy 18 and 0.48 (95% CI 0.43–0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.

Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study

Objective The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia). Design Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6 years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared. Results Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40 weeks. Conclusion The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the decline.

In utero exposure to maternal tobacco smoke and subsequent obesity, hypertension, and gestational diabetes among women in the MoBa Cohort

Background: Environmental factors influencing the developmental origins of health and disease need to be identified and investigated. In utero exposure to tobacco smoke has been associated with obesity and a small increase in blood pressure in children; however, whether there is a corresponding increased risk of conditions such as diabetes and hypertension during adulthood remains unclear. Objective: Our goal was to assess the association of self-reported in utero exposure to tobacco smoke with the prevalence of obesity, hypertension, type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) in women 14–47 years of age. Methods: We conducted a cross-sectional analysis of the Norwegian Mother and Child Cohort Study, which enrolled pregnant women in Norway from 1999 thorough 2008. Exposure to tobacco smoke in utero (yes vs. no) was ascertained on the baseline questionnaire (obtained at ~ 17 weeks’ gestation); the outcomes were ascertained from the Medical Birth Registry of Norway and the questionnaire. Our analysis included 74,023 women. Results: Women exposed to tobacco smoke in utero had 1.53 times the odds of obesity [95% confidence interval (CI): 1.45, 1.61] relative to those unexposed, after adjusting for age, education, and personal smoking. After further adjustment for body mass index, the odds ratio for hypertension was 1.68 (95% CI: 1.19, 2.39); for T2DM 1.14 (95% CI: 0.79, 1.65); and for GDM 1.32 (95% CI: 1.10, 1.58) among exposed compared with unexposed. Conclusions: Exposure to tobacco smoke in utero was associated with obesity, hypertension, and GDM in adult women. The possibility that the associations were attributable to unmeasured confounding cannot be excluded.

Registration of Down syndrome in the Medical Birth Registry of Norway: Validity and time trends

Objective. To validate Down syndrome registration in the Medical Birth Registry of Norway (MBRN), 2001–2005, and study time trends and geographical differences in Down syndrome prevalence,1967–2005. Design/setting. Population‐based cohort study, Norway. Population. 2.3 million pregnancies and births registered in the MBRN, 1967–2005. Methods. We linked data from the MBRN during 2001–2005 with data from Norways four laboratories of medical genetics. We calculated sensitivity and positive predictive values (PPV) of the MBRN registration overall, and by background variables. Prevalence rates from 1967 to 2005, overall and regional, were presented graphically as smoothed lowess estimates, crude and standardized for maternal age. Time trends were evaluated, adjusting for maternal age by logistic regression. Main outcome measures. Sensitivity, PPV, and prevalence rates. Results. Five hundred and seventy‐six verified cases of Down syndrome gave a prevalence of 2.0 per 1,000 among 288,213 births and terminations in the MBRN during 2001–2005. Of verified cases, 470 (81.6%) were registered with Down syndrome in the MBRN, while 470 (90.2%) of 521 MBRN‐registered cases were verified. Sensitivity was higher in the Northern (93.1%; p = 0.005) and Middle (90.6%; p = 0.02) region relative the Southern (76.3%), higher for mothers ≥35 years (92.9%) than younger ones (86.1%; p = 0.01), and higher for live births (88.8%) relative stillbirths (55.6%; p<0.001). When adjusting for maternal age, there were no significant time trends in prevalence rates from 1967 to 2005. Regional differences over time were found, probably representing reporting differences. Conclusions. Validity of registration in the MBRN was satisfactory during 2001–2005. Increasing prevalence rates over time were explained by increasing maternal age.

Maternal and paternal contribution to intergenerational recurrence of breech delivery: population based cohort study

Objective To investigate intergenerational recurrence of breech delivery, with a hypothesis that both women and men delivered in breech presentation contribute to increased risk of breech delivery in their offspring. Design Population based cohort study for two generations. Setting Data from the medical birth registry of Norway, based on all births in Norway 1967-2004 (2.2 million births). Participants Generational data were provided through linkage by national identification numbers, forming 451 393 mother-offspring units and 295 253 father-offspring units. We included units where both parents and offspring were singletons and offspring were first born, forming 232 704 mother-offspring units and 154 851 father-offspring units for our analyses. Main outcome measure Breech delivery in the second generation. Results Men and women who themselves were delivered in breech presentation had more than twice the risk of breech delivery in their own first pregnancies compared with men and women who had been cephalic presentations (odds ratios 2.2, 95% confidence interval 1.8 to 2.7, and 2.2, 1.9 to 2.5, for men and women, respectively). The strongest risks of recurrence were found for vaginally delivered offspring and were equally strong for men and women. Increased risk of recurrence of breech delivery in offspring was present only for parents delivered at term. Conclusion Intergenerational recurrence risk of breech delivery in offspring was equally high when transmitted through fathers and mothers. It seems reasonable to attribute the observed pattern of familial predisposition to term breech delivery to genetic inheritance, predominantly through the fetus.

Recent Decrease in the Prevalence of Congenital Heart Defects in Europe

OBJECTIVES To examine trends in the prevalence of congenital heart defects (CHDs) in Europe and to compare these trends with the recent decrease in the prevalence of CHDs in Canada (Quebec) that was attributed to the policy of mandatory folic acid fortification. STUDY DESIGN We used data for the period 1990-2007 for 47 508 cases of CHD not associated with a chromosomal anomaly from 29 population-based European Surveillance of Congenital Anomalies registries in 16 countries covering 7.3 million births. We estimated trends for all CHDs combined and separately for 3 severity groups using random-effects Poisson regression models with splines. RESULTS We found that the total prevalence of CHDs increased during the 1990s and the early 2000s until 2004 and decreased thereafter. We found essentially no trend in total prevalence of the most severe group (group I), whereas the prevalence of severity group II increased until about 2000 and decreased thereafter. Trends for severity group III (the most prevalent group) paralleled those for all CHDs combined. CONCLUSIONS The prevalence of CHDs decreased in recent years in Europe in the absence of a policy for mandatory folic acid fortification. One possible explanation for this decrease may be an as-yet-undocumented increase in folic acid intake of women in Europe following recommendations for folic acid supplementation and/or voluntary fortification. However, alternative hypotheses, including reductions in risk factors of CHDs (eg, maternal smoking) and improved management of maternal chronic health conditions (eg, diabetes), must also be considered for explaining the observed decrease in the prevalence of CHDs in Europe or elsewhere.

Prior adverse pregnancy outcome and the risk of stillbirth.

OBJECTIVE: To estimate whether a history of fetal growth restriction, abruptio placentae, preeclampsia, or live preterm birth is associated with excess risk of stillbirth in a subsequent pregnancy. We also estimated the maternal and paternal contributions to such effects. METHODS: This was a population-based cohort study from 1967 to 2005. Pairs of first and second, second and third, third and fourth, and fourth and fifth births were identified among all births from the Medical Birth Registry of Norway; 747,221 pairs with the same parents, 51,708 with the same mother and different father, and 65,602 with the same father and different mother. The associations of gestational age categories (22–27, 28–32, 33–36, and at or above 37 weeks), small for gestational age (SGA), preeclampsia, and abruptio placenta in the first pregnancy with stillbirth and late abortion in the second were assessed by odds ratios (ORs) obtained by logistic regression. RESULTS: The baseline rate of stillbirth during the study period was 1.0% of all births from 16 weeks of gestation. After births with gestational age 22–27, 28–32, and 33–36 weeks of gestation, stillbirth was six, three and two times more likely to occur than after a term birth (OR 5.7, 95% confidence interval [CI] 4.2–7.6; OR 2.6, 95% CI 2.1–3.3; and OR 1.7, 95% CI 1.5–1.9, respectively). Odds ratios of stillbirth subsequent to pregnancies with SGA, preeclampsia, and abruptio placentae were 1.7 (95% CI 1.6–1.9), 1.6 (95% CI 1.5–1.9), and 2.8 (95% CI 2.2–3.5), respectively, and increased with severity of the conditions. Gestational age below 33 weeks with preeclampsia or SGA carried 6–9 and 6–13-fold effects on later stillbirth, respectively. Men who fathered a pregnancy with preterm preeclampsia were significantly more likely to father a stillbirth in another woman (OR 2.4, 95% CI 1.1–5.5). CONCLUSION: Live preterm birth, fetal growth restriction, preeclampsia, and abruptio placenta are strongly associated with later stillbirth. LEVEL OF EVIDENCE: II

Recurrence of prolonged and post-term gestational age across generations: maternal and paternal contribution

Please cite this paper as: Morken N‐H, Melve K, Skjaerven R. Recurrence of prolonged and post‐term gestational age across generations: maternal and paternal contribution. BJOG 2011;118:1630–1635.

Infants' length at birth: an independent effect on perinatal mortality.

Aim. To investigate whether variations in birth length (crown‐heel‐length) were associated with perinatal mortality rate independent of birth weight.

Intergenerational birth weight associations by mother's birth order — The mechanisms behind the paradox: A population-based cohort study

BACKGROUND Mothers birth order is inversely associated with offspring birth weight despite positively associated with the mothers own birth weight. The causes behind this relation have not been elucidated. AIMS To investigate the relation between mothers birth order and birth weight of her offspring, with emphasis on possible mechanisms behind the findings. STUDY DESIGN Population based cohort study over two generations. SUBJECTS Data were from the Medical Birth Registry of Norway, based on all births in Norway, 1967-2006 (2.3 million births). Units where both mothers and offspring were singletons and offspring were first born were included, forming 272,674 mother-offspring units for the analyses. OUTCOME MEASURE Birth weight in the second generation. RESULTS Mothers birth weight increased steadily with increasing birth order from 3369 g for first born to 3538 g for fourth or later born mothers. In contrast, there was a monotonic decrease in offspring mean birth weight with increasing mothers birth order (9.1 g per birth order (95% C.I.; 6.8, 11.4)). First born mothers tended to be older, to have higher education, to more often be married or cohabiting, and to smoke less than later born mothers at the time of their first pregnancy. CONCLUSION The general reduction in mean birth weight among first born mothers was not observed in the next generation. We suggest that first born mothers have the same biologically potential for achieving similar sized offspring as later born mothers, and that social factors account for the inverse relation.