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.

Recurrence of stillbirth in sibships: Population-based cohort study.

Knowledge of stillbirth recurrence risk is of clinical interest and may give etiological insight. The authors studied "gestational age-" and "weight-by-gestation-specific" stillbirth recurrence, and evaluated time trends in a population-based cohort study from the Medical Birth Registry of Norway, from 1967 to 2004. Singleton births, including stillbirths from 20 weeks' gestation, were linked to their mothers by national identification numbers. Stillbirth rates in second pregnancies among mothers with (N = 5,091) and without (N = 562,057; the reference group) a stillbirth in first pregnancies were compared across 4 gestational age and 3 weight-by-gestation groups. A remarkable symmetric pattern of gestational age-specific recurrence of stillbirth was found, with highest odds of stillbirth in the same age group. The adjusted odds ratio values associated with preterm stillbirth recurrence were high, for example, 25.7 (95% confidence interval: 19.8, 33.3) for stillbirth at 20-27 weeks' gestation (73/1,511 vs. 1,021/562,057), while lower for term stillbirth: adjusted odds ratio = 2.3 (95% confidence interval: 1.2, 4.7) (9/1,844 vs. 1,021/538,499). The proportion of second early stillbirths in the population attributable to previous early stillbirth was 6.4%, compared with 0.5% for second term stillbirth. Over time, recurrence of early stillbirth decreased, whereas that of mid/late stillbirth did not change significantly. A symmetric pattern of recurring stillbirth in similar weight-by-gestation groups was not found.

Outcomes of pregnancies following a birth with major birth defects: a population based study.

BACKGROUND/AIM: Parents whose first infant had birth defects may worry about a new pregnancy. Our aim was to study pregnancy outcomes among non-malformed second siblings in families where the first birth had a major birth defect. METHODS: Data were from the Medical Birth Registry of Norway from 1967 to 2004. Births were linked to their mothers through the unique national identification numbers, providing sibship files with the mother as the observation unit. The study was based on 538,669 singleton first and second full siblings. Families were classified as affected families if the first infant had a major birth defect. Pregnancy outcomes for non-malformed second siblings following affected first births were compared with second siblings in families without malformed infants. Subgroup analyses were done for families where first infants had neural tube defects, cleft lip with or without cleft palate, abdominal wall defects, limb reduction defects, pes equinovarus and congenital dysplasia of the hip. RESULTS: Second siblings in affected families did not differ from those in unaffected families in risk of perinatal death, small for gestational age, preterm birth, placental abruption or preeclampsia. Second siblings following an infant with limb reduction defects had a higher risk of breech presentation than second siblings in unaffected families, also when stratifying on previous siblings in vertex presentation (stratified OR 2.20 [95% C.I. 1.17-4.15]). CONCLUSION: Parents who proceed to a new pregnancy after a first birth with birth defects may be reassured that, given no recurring defects, there is in general no increased risk of adverse pregnancy outcomes.

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 Norway's 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 > or =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.

Birthweight and perinatal mortality: paradoxes, social class, and sibling dependencies.

BACKGROUND: Birthweight distributions among second-born infants depend on the birthweights of older siblings, with implications for weight-specific perinatal mortality. We wanted to study whether these relations were explained by socioeconomic levels, and to study time trends in a situation with decreasing perinatal mortality rates. METHODS: Births in the Norwegian Medical Birth Registry from 1967 to 1998 were linked to their mothers through their national identification numbers. The study population was 546 688 mothers with at least two singletons weighing >/==" BORDER="0">500 g at birth. Weight-specific perinatal mortality for second-born siblings in families with first-born siblings in either the highest or the lowest birthweight quartile was analysed. Maternal education and cohabitation status were used as measures of socioeconomic level. RESULTS: For all 500-g categories below 3500 g, mortality rates were significantly higher among second-born infants with an older sibling in the highest rather than the lowest weight quartile. This pattern was the same across three educational levels. The exclusion of preterm births did not change the effect pattern. A comparison of perinatal mortality among second siblings in terms of relative birthweight (z-scores) showed a reversal of the relative risks, although these were only significantly different from unity for the smallest infants. Conclusion The crossover in weight-specific perinatal mortality for second siblings by weight of first sibling is largely independent of socioeconomic level, and is not weakened by the decreasing perinatal mortality rates in the population over time. Family data should be taken into consideration when evaluating the risk of adverse pregnancy outcome relating to weight.

Intergenerational birth weight associations by mother's birth order - the mechanisms behind the paradox: a population-based cohort study.

BACKGROUND: Mother's birth order is inversely associated with offspring birth weight despite positively associated with the mother's own birth weight. The causes behind this relation have not been elucidated. AIMS: To investigate the relation between mother's 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: Mother's 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 mother's 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.

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.

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.

Genetic and environmental influences on birth weight, birth length, head circumference, and gestational age by use of population-based parent-offspring data.

Familial correlations in birth weight and gestational age have been explained by fetal and maternal genetic factors, mainly in studies on offspring of twins. The aim of the present intergenerational study was to estimate and compare fetal and maternal genetic effects and shared sibling environmental effects on birth weight and gestational age and also on crown-heel length and head circumference. The authors used path analysis and maximum likelihood principles to estimate these effects and, at the same time, to adjust for covariates. Parent-offspring data were obtained from the Medical Birth Registry of Norway from 1967 to 2004. For the analysis of birth weight and crown-heel length, 101,748 families were included; for gestational age, 91,617 families; and for head circumference, 77,044 families. Assuming no cultural transmission and random mating, the authors found that fetal genetic factors explained 31% of the normal variation in birth weight and birth length, 27% of the variation in head circumference, and 11% of the variation in gestational age. Maternal genetic factors explained 22% of the variation in birth weight, 19% of the variation in birth length and head circumference, and 14% of the variation in gestational age. Relative to the proportion of explained variation, fetal genes were most important for birth length and head circumference.

Families with birth defects: is birth weight of nonmalformed siblings affected?

Infants with congenital malformations have on average lower birth weight than do infants without malformations. Preterm delivery and low birth weight are known to recur in sibships. The aim of the study was to compare the birth weight of siblings to malformed infants with the birth weight of infants in families without malformed infants. Data were from the Medical Birth Registry in Norway from 1967 to 1998. Births were linked to their mothers through the unique personal identification number, providing sibship files with the mother as the observation unit. The study was based on 551,478 mothers with at least two singleton infants and 209,423 mothers with at least three singletons. The authors grouped the families according to whether and in which birth order an infant had a registered congenital malformation and compared birth weight and gestational age between infants of the same birth order in families with malformations and without. Overall, in families where one or two infants had a congenital malformation, the crude and adjusted mean birth weight of nonmalformed siblings did not differ from that of infants in unaffected families, whereas it was significantly reduced for the malformed infant itself. We conclude that reduced birth weight associated with congenital anomalies is specific to the affected pregnancy.

Families with a perinatal death: is there an association between the loss and the birthweight of surviving siblings?

Our objective was to study birthweight among surviving siblings in families with and without a perinatal loss, and to evaluate whether different causes of death were associated with the results. Data were for 1967-98 from the Norwegian Medical Birth Registry. Births were organised with the mother as the observation unit through the personal identification number, providing sibship files. We analysed 550 930 sibships with at least two singletons, 208 586 sibships with at least three singletons and 45 675 sibships with at least four singleton births. We compared mean birthweight and gestational age between infants in sibships with and without a perinatal loss, total losses and the different causes of death. Surviving siblings in families with a perinatal loss had significantly lower mean birthweights than their counterparts in unaffected families, after adjusting for gestational age, interpregnancy interval, time period and marital status. An exception was found when cause of death was a birth defect, when growth retardation among surviving siblings was not found on average. We conclude that families who have lost an infant because of a birth defect do not appear to have an increased risk of adverse birth outcome associated with growth restriction.