Recurrence of postpartum hemorrhage in relatives: A population-based cohort study

Introduction Studies on the family aggregation of postpartum hemorrhage (PPH) are scarce and with inconsistent results, and to what extent current birthweight influences recurrence between relatives remains to be studied. Further, family aggregation of PPH has been studied from an individual, but not from a public heath perspective. We aimed to investigate family aggregation of PPH in Norway, how birthweight influences these effects, and to estimate the proportion of PPH cases attributable to a family history of PPH and current birthweight. Material and methods Using data from the Medical Birth Registry of Norway, Statistics Norway, and Central Population Registry of Norway we identified individuals as newborns, parents, grandparents, and full and half-siblings, and studied 1 002 687 mother–offspring, 841 164 father–offspring, and 761 011 both-parents–offspring pairs. We used multilevel logistic regression to calculate odds ratios (OR) with 95% CI. Results If the birth of the mother but not of the father involved PPH, then the OR of PPH (>500 mL) in the next generation was 1.44 (95% CI 1.39–1.49). If the birth of the father but not of the mother involved PPH, then OR was 1.12 (95% CI 1.08–1.16). These effects were stronger in severe PPH. Recurrence between siblings was highest between full sisters (OR 1.47, 95% CI 1.41–1.52), followed by maternal half-sisters, paternal half-sisters, and partners of full brothers. A family history of PPH or birthweight of 4000 g or more accounted for ≤5% and 15% of the total number of PPH cases, respectively. Conclusions A history of PPH in relatives influenced the recurrence risk of PPH in a dose–response pattern consistent with the anticipated proportion of shared genes. The recurrence was highest through the maternal line.publishedVersio

Recurrence of postpartum hemorrhage, maternal and paternal contribution, and the effect of offspring birthweight and sex: a population-based cohort study

Purpose: This study examines individual aggregation of postpartum hemorrhage (PPH), paternal contribution and how offspring birthweight and sex influence recurrence of PPH. Further, we wanted to estimate the proportion of PPH cases attributable to a history of PPH or current birthweight. Methods: We studied all singleton births in Norway from 1967 to 2017 using data from Norwegian medical and administrational registries. Subsequent births in the parents were linked. Multilevel logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PPH defined as blood loss > 500 ml, blood loss > 1500 ml, or the need for blood transfusion in parous women. Main exposures were previous PPH, high birthweight, and fetal sex. We calculated adjusted population attributable fractions for previous PPH and current high birthweight. Results: Mothers with a history of PPH had three- and sixfold higher risks of PPH in their second and third deliveries, respectively (adjusted OR 2.9; 95% CI 2.9–3.0 and 6.0; 5.5–6.6). Severe PPH (> 1500 ml) had the highest risk of recurrence. The paternal contribution to recurrence of PPH in deliveries with two different mothers was weak, but significant. If the neonate was male, the risk of PPH was reduced. A history of PPH or birthweight ≥ 4000 g each accounted for 15% of the total number of PPH cases. Conclusion: A history of PPH and current birthweight exerted strong effects at both the individual and population levels. Recurrence risk was highest for severe PPH. Occurrence and recurrence were lower in male fetuses, and the paternal influence was weak.publishedVersio

Parental education and the risk of cerebral palsy for children:an evaluation of causality

Aim To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. Method We used data from Norwegian registries on approximately 1.5 million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family‐based matched case–control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. Results In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60–0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67–0.85 for paternal education). In the family‐based case–control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64–0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. Interpretation A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents’ educational level.publishedVersio

Familial risk of cerebral palsy: Population based cohort study

Objective To investigate risks of recurrence of cerebral palsy in family members with various degrees of relatedness to elucidate patterns of hereditability. Design Population based cohort study. Setting Data from the Medical Birth Registry of Norway, linked to the Norwegian social insurance scheme to identify cases of cerebral palsy and to databases of Statistics Norway to identify relatives. Participants 2 036 741 Norwegians born during 1967-2002, 3649 of whom had a diagnosis of cerebral palsy; 22 558 pairs of twins, 1 851 144 pairs of first degree relatives, 1 699 856 pairs of second degree relatives, and 5 165 968 pairs of third degree relatives were identified. Main outcome measure Cerebral palsy. Results If one twin had cerebral palsy, the relative risk of recurrence of cerebral palsy was 15.6 (95% confidence interval 9.8 to 25) in the other twin. In families with an affected singleton child, risk was increased 9.2 (6.4 to 13)-fold in a subsequent full sibling and 3.0 (1.1 to 8.6)-fold in a half sibling. Affected parents were also at increased risk of having an affected child (6.5 (1.6 to 26)-fold). No evidence was found of differential transmission through mothers or fathers, although the study had limited power to detect such differences. For people with an affected first cousin, only weak evidence existed for an increased risk (1.5 (0.9 to 2.7)-fold). Risks in siblings or cousins were independent of sex of the index case. After exclusion of preterm births (an important risk factor for cerebral palsy), familial risks remained and were often stronger. Conclusions People born into families in which someone already has cerebral palsy are themselves at elevated risk, depending on their degree of relatedness. Elevated risk may extend even to third degree relatives (first cousins). The patterns of risk suggest multifactorial inheritance, in which multiple genes interact with each other and with environmental factors. These data offer additional evidence that the underlying causes of cerebral palsy extend beyond the clinical management of delivery

Single umbilical artery and risk of congenital malformations: a population-based study in Norway.

Objectives: Single umbilical artery (SUA) is associated with congenital malformations in most organ systems, but reported findings have not been consistent. While it has been suggested that genetic and persisting environmental factors influence the development of SUA, it is not known whether there is an increased risk of recurrence in a subsequent pregnancy of the same woman. The aims of this study were to investigate the occurrence of, and risk factors for, SUA in Norway, to assess its association with congenital malformations and trisomies 13, 18 and 21 and to study the risk of recurrence of SUA in subsequent pregnancies. Methods: This was a population‐based study of all (n  = 918 933) singleton pregnancies of > 16 weeks' gestation recorded in the Medical Birth Registry of Norway from 1999 to 2014. To identify risk factors and congenital malformations associated with SUA, generalized estimating equations and logistic regression were used to calculate odds ratios (OR) with 95% CIs. ORs were also calculated for the recurrence of SUA in subsequent pregnancy. Results: The occurrence of SUA in our population was 0.46% (4241/918 933). Parity ≥ 4, smoking, maternal pregestational diabetes, epilepsy, chronic hypertension, previous Cesarean delivery and conception by assisted reproductive technology increased the odds of having SUA. There was a particularly strong association between SUA and gastrointestinal atresia or stenosis in the neonate, with ORs of 25.8 (95% CI, 17.0–39.1) and 20.3 (95% CI, 13.4–30.9) for esophageal and anorectal atresia or stenosis, respectively, followed by an OR of 5.9 (95% CI, 1.9–18.5) for renal agenesis. SUA was associated with an up to 7–8 times increased risk of congenital heart defects. There was an association with microcephaly, congenital hydrocephalus and other congenital malformations of the brain and spinal cord. Diaphragmatic hernia, limb reductions and cleft lip or palate had a weaker association with SUA, with ORs ranging from 4.8 to 2.8. The associations with trisomy 18 and 13 were equally strong (OR 14.4 (95% CI, 9.3–22.4) and OR 13.6 (95% CI, 6.7–27.8), respectively), and the risk of trisomy 21 was doubled (OR 2.1 (95% CI, 1.2–3.6)). Pregnancies with SUA, with or without an associated malformation, had a 2‐fold increased risk for SUA in a subsequent pregnancy. Conclusions: SUA is associated strongly with gastrointestinal atresia or stenosis, suggesting common developmental mechanisms. The increased risk of recurrence of SUA suggests that genetic and/or persisting environmental factors influence the risk. We found that SUA had equally strong associations with trisomies 13 and 18

Single umbilical artery and risk of congenital malformations: a population-based study in Norway.

Objectives: Single umbilical artery (SUA) is associated with congenital malformations in most organ systems, but reported findings have not been consistent. While it has been suggested that genetic and persisting environmental factors influence the development of SUA, it is not known whether there is an increased risk of recurrence in a subsequent pregnancy of the same woman. The aims of this study were to investigate the occurrence of, and risk factors for, SUA in Norway, to assess its association with congenital malformations and trisomies 13, 18 and 21 and to study the risk of recurrence of SUA in subsequent pregnancies. Methods: This was a population‐based study of all (n  = 918 933) singleton pregnancies of > 16 weeks' gestation recorded in the Medical Birth Registry of Norway from 1999 to 2014. To identify risk factors and congenital malformations associated with SUA, generalized estimating equations and logistic regression were used to calculate odds ratios (OR) with 95% CIs. ORs were also calculated for the recurrence of SUA in subsequent pregnancy. Results: The occurrence of SUA in our population was 0.46% (4241/918 933). Parity ≥ 4, smoking, maternal pregestational diabetes, epilepsy, chronic hypertension, previous Cesarean delivery and conception by assisted reproductive technology increased the odds of having SUA. There was a particularly strong association between SUA and gastrointestinal atresia or stenosis in the neonate, with ORs of 25.8 (95% CI, 17.0–39.1) and 20.3 (95% CI, 13.4–30.9) for esophageal and anorectal atresia or stenosis, respectively, followed by an OR of 5.9 (95% CI, 1.9–18.5) for renal agenesis. SUA was associated with an up to 7–8 times increased risk of congenital heart defects. There was an association with microcephaly, congenital hydrocephalus and other congenital malformations of the brain and spinal cord. Diaphragmatic hernia, limb reductions and cleft lip or palate had a weaker association with SUA, with ORs ranging from 4.8 to 2.8. The associations with trisomy 18 and 13 were equally strong (OR 14.4 (95% CI, 9.3–22.4) and OR 13.6 (95% CI, 6.7–27.8), respectively), and the risk of trisomy 21 was doubled (OR 2.1 (95% CI, 1.2–3.6)). Pregnancies with SUA, with or without an associated malformation, had a 2‐fold increased risk for SUA in a subsequent pregnancy. Conclusions: SUA is associated strongly with gastrointestinal atresia or stenosis, suggesting common developmental mechanisms. The increased risk of recurrence of SUA suggests that genetic and/or persisting environmental factors influence the risk. We found that SUA had equally strong associations with trisomies 13 and 18

Variation in use of Caesarean section in Norway: An application of spatio-temporal Gaussian random fields

Aims: Caesarean section (CS) is a medical intervention performed in Norway when a surgical delivery is considered more beneficial than a vaginal. Because deliveries with higher risk are centralized to larger hospitals, use of CS varies considerably between hospitals. We describe how the use of CS varies geographically by municipality. Since indications for CS should have little variation across the relatively homogenous population of Norway, we expect fair use of CS to be evenly distributed across the municipalities. Methods: Data from the Medical Birth Registry of Norway were used in our analyses (810,914 total deliveries, 133,746 CSs, 440 municipalities). We propose a spatial correlation model that takes the location into account to describe the variation in use of CS across the municipalities. The R packages R-INLA and TMB are used to estimate the yearly municipal CS rate and the spatial correlation between the municipalities. We also apply stratified models for different categories of delivering women (Robson groups). Estimated rates are displayed in maps and model parameters are shown in tables. Results: The CS rate varies substantially between the different municipalities. As expected, there was strong correlation between neighbouring municipalities. Similar results were found for different Robson groups. Conclusions: The substantial difference in CS use across municipalities in Norway is not likely to be due to specific medical reasons, but rather to hospitals’ different policies towards the use of CS. The policy to be either more or less restrictive to CS was not specific to any category of deliveries

Paternal country of origin and adverse neonatal outcomes in births to foreign-born women in Norway: A population-based cohort study

Background Migration is a risk factor for adverse neonatal outcomes. The various impacts of maternal origin have been reported previously. The aim of this study was to investigate associations between paternal origin and adverse neonatal outcomes in births to migrant and Norwegian-born women in Norway. Methods and findings This nationwide population-based study included births to migrant (n = 240,759, mean age 29.6 years [±5.3 SD]) and Norwegian-born women (n = 1,232,327, mean age 29.0 years [±5.1 SD]) giving birth in Norway in 1990–2016. The main exposure was paternal origin (Norwegian-born, foreign-born, or unregistered). Neonatal outcomes were very preterm birth (22+0–31+6 gestational weeks), moderately preterm birth (32+0–36+6 gestational weeks), small for gestational age (SGA), low Apgar score (<7 at 5 minutes), and stillbirth. Associations were investigated in migrant and Norwegian-born women separately using multiple logistic regression and reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs), adjusted for year of birth, parity, maternal and paternal age, marital status, maternal education, and mother’s gross income. In births to migrant women, a foreign-born father was associated with increased odds of very preterm birth (1.1% versus 0.9%, aOR 1.20; CI 1.08–1.33, p = 0.001), SGA (13.4% versus 9.5%, aOR 1.48; CI 1.43–1.53, p < 0.001), low Apgar score (1.7% versus 1.5%, aOR 1.14; CI 1.05–1.23, p = 0.001), and stillbirth (0.5% versus 0.3%, aOR 1.26; CI 1.08–1.48, p = 0.004) compared with a Norwegian-born father. In Norwegian-born women, a foreign-born father was associated with increased odds of SGA (9.3% versus 8.1%, aOR 1.13; CI 1.09–1.16, p < 0.001) and decreased odds of moderately preterm birth (4.3% versus 4.4%, aOR 0.95; CI 0.91–0.99, p = 0.015) when compared with a Norwegian-born father. In migrant women, unregistered paternal origin was associated with increased odds of very preterm birth (2.2% versus 0.9%, aOR 2.29; CI 1.97–2.66, p < 0.001), moderately preterm birth (5.6% versus 4.7%, aOR 1.15; CI 1.06–1.25, p = 0.001), SGA (13.0% versus 9.5%, aOR 1.50; CI 1.42–1.58, p < 0.001), low Apgar score (3.4% versus 1.5%, aOR 2.23; CI 1.99–2.50, p < 0.001), and stillbirth (1.5% versus 0.3%, aOR 4.87; CI 3.98–5.96, p < 0.001) compared with a Norwegian-born father. In Norwegian-born women, unregistered paternal origin was associated with increased odds of very preterm birth (4.6% versus 1.0%, aOR 4.39; CI 4.05–4.76, p < 0.001), moderately preterm birth (7.8% versus 4.4%, aOR 1.62; CI 1.53–1.71, p < 0.001), SGA (11.4% versus 8.1%, aOR 1.30; CI 1.24–1.36, p < 0.001), low Apgar score (4.6% versus 1.3%, aOR 3.51; CI 3.26–3.78, p < 0.001), and stillbirth (3.2% versus 0.4%, aOR 9.00; CI 8.15–9.93, p < 0.001) compared with births with a Norwegian-born father. The main limitations of this study were the restricted access to paternal demographics and inability to account for all lifestyle factors. Conclusion We found that a foreign-born father was associated with adverse neonatal outcomes among births to migrant women, but to a lesser degree among births to nonmigrant women, when compared with a Norwegian-born father. Unregistered paternal origin was associated with higher odds of adverse neonatal outcomes in births to both migrant and nonmigrant women when compared with Norwegian-born fathers. Increased attention to paternal origin may help identify women in maternity care at risk for adverse neonatal outcomes