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.

Spectrum of congenital anomalies in pregnancies with pregestational diabetes.

BACKGROUND: Maternal pregestational diabetes is a well-known risk factor for congenital anomalies. This study analyses the spectrum of congenital anomalies associated with maternal diabetes using data from a large European database for the population-based surveillance of congenital anomalies. METHODS: Data from 18 population-based EUROCAT registries of congenital anomalies in 1990-2005. All malformed cases occurring to mothers with pregestational diabetes (diabetes cases) were compared to all malformed cases in the same registry areas to mothers without diabetes (non-diabetes cases). RESULTS: There were 669 diabetes cases and 92,976 non diabetes cases. Odds ratios in diabetes pregnancies relative to non-diabetes pregnancies comparing each EUROCAT subgroup to all other non-chromosomal anomalies combined showed significantly increased odds ratios for neural tube defects (anencephaly and encephalocele, but not spina bifida) and several subgroups of congenital heart defects. Other subgroups with significantly increased odds ratios were anotia, omphalocele and bilateral renal agenesis. Frequency of hip dislocation was significantly lower among diabetes (odds ratio 0.15, 95% CI 0.05-0.39) than non-diabetes cases. Multiple congenital anomalies were present in 13.6 % of diabetes cases and 6.1 % of non-diabetes cases. The odds ratio for caudal regression sequence was very high (26.40,95% CI 8.98-77.64), but only 17% of all caudal regression cases resulted from a pregnancy with pregestational diabetes. CONCLUSIONS: The increased risk of congenital anomalies in pregnancies with pregestational diabetes is related to specific non-chromosomal congenital anomalies and multiple congenital anomalies and not a general increased risk.

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.

International trends of Down syndrome 1993-2004: Births in relation to maternal age and terminations of pregnancies.

BACKGROUND: The aim of this study was to examine trends of Down syndrome (DS) in relation to maternal age and termination of pregnancies (ToP) in 20 registries of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). METHODS: Trends of births with DS (live-born and stillborn), ToP with DS, and maternal age (percentage of mothers older than 35 years) were examined by year over a 12-year period (1993-2004). The total mean number of births covered was 1550,000 annually. RESULTS: The mean percentage of mothers older than 35 years of age increased from 10.9% in 1993 to 18.8% in 2004. However, a variation among the different registers from 4-8% to 20-25% of mothers >35 years of age was found. The total mean prevalence of DS (still births, live births, and ToP) increased from 13.1 to 18.2/10,000 births between 1993 and 2004. The total mean prevalence of DS births remained stable at 8.3/10,000 births, balanced by a great increase of ToP. In the registers from France, Italy, and the Czech Republic, a decrease of DS births and a great increase of ToP was observed. The number of DS births remained high or even increased in Canada Alberta, and Norway during the study period. CONCLUSIONS: Although an increase in older mothers was observed in most registers, the prevalence of DS births remained stable in most registers as a result of increasing use of prenatal diagnostic procedures and ToP with DS.

Mothers' and fathers' birth characteristics and perinatal mortality in their offspring: a population-based cohort study.

There is increasing interest in the associations between parental birthweight and gestational age with their perinatal outcomes. We investigated perinatal mortality risk in offspring in relation to maternal and paternal gestational age and birthweight. We used population-based generational data from the Medical Birth Registry of Norway, 1967-2006. Singletons in both generations were included, forming 520,794 mother-offspring and 376,924 father-offspring units. Perinatal mortality in offspring was not significantly associated with paternal gestational age or birthweight, whereas it was inversely associated with maternal gestational age. A threefold increased risk in perinatal mortality was found among offspring of mothers born at 28-30 weeks of gestation relative to offspring of mothers born at term (37-43 weeks) (relative risk: 2.9, 95% CI 1.9, 4.6). There was also an overall association between maternal birthweight and offspring perinatal mortality. Relative risk for mothers whose birthweight was <2000 g was 1.5 (95% CI 1.1, 1.9), relative to mothers whose birthweight was 3500-3999 g. However, confined to mothers born at >or=34 weeks of gestation, the birthweight association was not significant. Weight-specific perinatal mortality in offspring was dependent on the birthweight of the mother and the father, that is, offspring who were small relative to their mother's or father's birthweight had increased perinatal mortality. In conclusion, a mother's gestational age, and not her birthweight, was significantly associated with perinatal mortality in the offspring, while there was no such association for the father.

Self-selection and bias in a large prospective pregnancy cohort in Norway.

Self-selection in epidemiological studies may introduce selection bias and influence the validity of study results. To evaluate potential bias due to self-selection in a large prospective pregnancy cohort in Norway, the authors studied differences in prevalence estimates and association measures between study participants and all women giving birth in Norway. Women who agreed to participate in the Norwegian Mother and Child Cohort Study (43.5% of invited; n = 73 579) were compared with all women giving birth in Norway (n = 398 849) using data from the population-based Medical Birth Registry of Norway in 2000-2006. Bias in the prevalence of 23 exposure and outcome variables was measured as the ratio of relative frequencies, whereas bias in exposure-outcome associations of eight relationships was measured as the ratio of odds ratios. Statistically significant relative differences in prevalence estimates between the cohort participants and the total population were found for all variables, except for maternal epilepsy, chronic hypertension and pre-eclampsia. There was a strong under-representation of the youngest women (<25 years), those living alone, mothers with more than two previous births and with previous stillbirths (relative deviation 30-45%). In addition, smokers, women with stillbirths and neonatal death were markedly under-represented in the cohort (relative deviation 22-43%), while multivitamin and folic acid supplement users were over-represented (relative deviation 31-43%). Despite this, no statistically relative differences in association measures were found between participants and the total population regarding the eight exposure-outcome associations. Using data from the Medical Birth Registry of Norway, this study suggests that prevalence estimates of exposures and outcomes, but not estimates of exposure-outcome associations are biased due to self-selection in the Norwegian Mother and Child Cohort Study.

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.

Reduced fertility after cesarean delivery: a maternal choice.

OBJECTIVE: To explore the association between mode of delivery and subsequent fertility. METHODS: Deliveries registered in the Medical Birth Registry of Norway were linked to mothers through national identification numbers. The study population was 596,341 women who had their first delivery during 1967-1996, and who were followed up through 2003. We compared rates of continuation to a subsequent birth according to mode of previous delivery (cesarean compared with vaginal). RESULTS: If the first child survived the first year of life, cesarean delivery was associated with a significantly reduced probability of a second birth (relative risk [RR] 0.82, 95% confidence interval [CI] 0.81-0.83 during 1967-1981, and RR 0.88, 95% CI 0.88-0.89 during 1982-1996). Following a stillbirth or an infant loss, the association was less strong during 1967-1981 (RR 0.93, 95% CI 0.89-0.97) and no longer significant during 1982-1996 (RR 1.00, 95% CI 0.97-1.03). A similar pattern was observed from the second to the third birth and in subgroup analyses of women with preeclampsia or breech presentation and in an obstetric low-risk group. CONCLUSION: Cesarean delivery was more strongly associated with reduced fertility if the infant survived than if it was stillborn or died. This suggests that the reduced fertility was to a large degree voluntary and not related to the indication, nor to any physical consequence, of the cesarean delivery. LEVEL OF EVIDENCE: II.

Parenthood in survivors after adulthood cancer and perinatal health in their offspring: a preliminary report.

Cancer survivors may fear infertility, obstetric problems, and genetic alterations in their offspring. After linkage of three registries the probability of post-treatment parenthood and the risk of obstetric and perinatal problems were estimated in cancer survivors compared to individuals without a cancer diagnosis. A total of 1531 of 13,817 patients had 2307 children after one parent's cancer diagnosis: 972 males had 1479 children and 559 females had 828. A total of 1217 patients (784 males and 433 females) became parents > or =9 months after the diagnosis (1899 births: 1221 to male cancer patients and 678 to female patients). The post-diagnosis parenthood probability was 8% at 5 years, and 14% at 10 years without further increase. Female cancer survivors gave birth to post-diagnosis infants with on average 130 grams lower birth weight and 6 days shorter gestations compared with infants in the non-cancer population. Infants fathered by male cancer survivors did not differ from control infants with respect to birth weight or gestational age. There was no increase in the prevalence of major congenital malformations in the offspring of cancer survivors as compared with the offspring of the non-cancer population. Multiple births and deliveries by cesarean sections were increased. Parenthood after cancer is possible in a significant number of patients, more so for males than females. The risk of major congenital malformations was not increased relative to the non-cancer population, nor was perinatal mortality increased. However, female cancer survivors delivered more preterm births and low-birth-weight infants than what was found in the non-cancer population.

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.

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 10000 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.

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.

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.

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.