Sensorineural hearing impairment among preterm children: a Norwegian population-based study.

OBJECTIVE: To investigate the risk for sensorineural hearing impairment (SNHI) in preterm infants, and to what extent the risk is attributed to perinatal morbidities and therapies. DESIGN: Population-based cohort study using data from several nationwide registries. SETTING: Norwegian birth cohort 1999-2014, with data on SNHI until 2019. PARTICIPANTS: 60 023 live-born preterm infants, divided in moderate-late preterm (MLP) infants (32-36 weeks), very preterm (VP) infants (28-31 weeks) and extremely preterm (EP) infants (22-27 weeks), and a reference group with all 869 797 term-born infants from the study period. MAIN OUTCOME MEASURES: SNHI defined by selected ICD-10 codes, recorded during minimum 5-year observation period after birth. RESULTS: The overall SNHI prevalence in the preterm cohort was 1.4% compared with 0.7% in the reference group. The adjusted risk ratios (95% CIs) for SNHI were 1.7 (1.5-1.8) in MLP infants, 3.3 (2.8-3.9) in VP infants and 7.6 (6.3-9.1) in EP infants. Among EP infants, decreasing gestational age was associated with a steep increase in the risk ratio of SNHI reaching 14.8 (7.7-28.7) if born at 22-23 weeks gestation. Among the VP and MLP infants, mechanical ventilation and antibiotic therapy had strongest association with increased risk of SNHI, but infants not receiving these therapies remained at increased risk. Among EP infants intracranial haemorrhage increased the already high risk for SNHI. We found no signs of delayed or late-onset SNHI in preterm infants. CONCLUSION: Preterm birth is an independent risk factor for SNHI. Invasive therapies and comorbidities increase the risk, predominantly in infants born after 28 weeks gestation.

Hearing impairment after asphyxia and neonatal encephalopathy: a Norwegian population-based study.

The purpose of this study is to evaluate the association between perinatal asphyxia, neonatal encephalopathy, and childhood hearing impairment. This is a population-based study including all Norwegian infants born ≥ 36 weeks gestation between 1999 and 2014 and alive at 2 years (n = 866,232). Data was linked from five national health registries with follow-up through 2019. Perinatal asphyxia was defined as need for neonatal intensive care unit (NICU) admission and an Apgar 5-min score of 4-6 (moderate) or 0-3 (severe). We coined infants with seizures and an Apgar 5-min score < 7 as neonatal encephalopathy with seizures. Infants who received therapeutic hypothermia were considered to have moderate-severe hypoxic-ischemic encephalopathy (HIE). The reference group for comparisons were non-admitted infants with Apgar 5-min score ≥ 7. We used logistic regression models and present data as adjusted odds ratios (aORs) with 95% confidence intervals (CI). The aOR for hearing impairment was increased in all infants admitted to NICU: moderate asphyxia aOR 2.2 (95% CI 1.7-2.9), severe asphyxia aOR 5.2 (95% CI 3.6-7.5), neonatal encephalopathy with seizures aOR 7.0 (95% CI 2.6-19.0), and moderate-severe HIE aOR 10.7 (95% CI 5.3-22.0). However, non-admitted infants with Apgar 5-min scores < 7 did not have increased OR of hearing impairment. The aOR for hearing impairment for individual Apgar 5-min scores in NICU infants increased with decreasing Apgar scores and was 13.6 (95% CI 5.9-31.3) when the score was 0.          Conclusions: An Apgar 5-min score < 7 in combination with NICU admission is an independent risk factor for hearing impairment. Children with moderate-severe HIE had the highest risk for hearing impairment. What is Known: • Perinatal asphyxia and neonatal encephalopathy are associated with an increased risk of hearing impairment. • The strength of the association, and how other co-morbidities affect the risk of hearing impairment, is poorly defined. What is New: • Among neonates admitted to a neonatal intensive care unit (NICU), decreased Apgar 5-min scores, and increased severity of neonatal encephalopathy, were associated with a gradual rise in risk of hearing impairment. • Neonates with an Apgar 5-min score 7, but without NICU admission, did not have an increased risk of hearing impairment.

Variation in antibiotic consumption in very preterm infants-a 10 year population-based study.

OBJECTIVES: Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. PATIENTS AND METHODS: All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009-18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. RESULTS: We included 5296 infants: 3646 (69%) were born at 28-31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum ß-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum ß-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum ß-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. CONCLUSIONS: The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum ß-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development.

Risk factors and recurrence of cause-specific postpartum hemorrhage: A population-based study.

OBJECTIVE: To explore risk profiles of the different types of postpartum hemorrhage (PPH >500ml or severe PPH >1500ml) and their recurrence risks in a subsequent delivery. METHODS: With data from The Medical Birth Registry of Norway and Statistics Norway we performed a population-based cohort study including all singleton deliveries in Norway from 1967-2017. Multilevel logistic regression was used to calculate odds ratio (OR), with 95% confidence interval (CI), with different PPH types (PPH >500ml or PPH >1500ml (severe PPH) combined with retained placenta, uterine atony, obstetric trauma, dystocia, or undefined cause) as outcomes. RESULT: We identified 277 746 PPH cases of a total of 3 003 025 births (9.3%) from 1967 to 2017. Retained placenta (and/or membranes) was most often registered as severe PPH (29.3%). Maternal, fetal, and obstetric characteristics showed different associations with the PPH types. Male sex of the neonate was associated with reduced risk of PPH. This effect was strongest on PPH due to retained placenta (adjusted OR, (aOR): 0.80, 95% CI 0.78-0.82), atony (aOR 0.92, 95% CI: 0.90-0.93) and PPH with undefined cause (aOR 0.96, 95% CI: 0.95-0.97). Previous cesarean section showed a strong association with PPH due to dystocia (aOR of 13.2, 95% CI: 12.5-13.9). Recurrence risks were highest for the same type: PPH associated with dystocia (aOR: 6.8, 95% CI: 6.3-7.4), retained placenta and/or membranes (aOR: 5.9, 95% CI: 5.5-6.4), atony (aOR: 4.0, 95% CI: 3.8-4.2), obstetric trauma (aOR: 3.9, 95% CI: 3.5-4.3) and PPH of undefined cause (aOR: 2.2, 95% CI: 2.1-2.3). CONCLUSION: Maternal, fetal and obstetric characteristics had differential effects on types of PPH. Recurrence differed considerably between PPH types. Retained placenta was most frequently registered with severe PPH, and showed strongest effect of sex; delivery of a boy was associated with lower risk of PPH. Previous cesarean increased the risk of PPH due to dystocia.

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.

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.

The limits of small-for-gestational-age as a high-risk category.

SGA (small for gestational age) is widely used to identify high-risk infants, although with inconsistent definitions. Cut points range from 2.5th to 10th percentile of birthweight-for-gestational age. We used receiver operator characteristic curves (ROC) to identify the cut point with maximum sensitivity and specificity (Youden Index), and the area under the curve (AUC), which assesses overall discriminating power. Analysis was conducted on 3,836,034 US births (2015) and 292,279 Norwegian births (2010-14). Birthweight percentiles were calculated using exact birthweights at each week of gestational age, and then summarized across gestational ages. We also conducted a companion analysis of gestational age itself to consider the predictive power of gestational week of birth. Outcomes were neonatal mortality and cerebral palsy, both strongly associated with birthweight. Birthweight percentiles performed poorly in all analyses. The AUC for birthweight percentiles as a discriminator of neonatal mortality was 60% (where 50% is no better than a coin-toss). At such low discrimination, the Youden Index provides no useful SGA cut point. Results in Norway were virtually identical, with an AUC of 58%. The AUC with cerebral palsy as the outcome was even lower, at 54%. In contrast, gestational age had an AUC of 85% as a predictor of neonatal mortality, with < 37 weeks as the optimum cut point. SGA provides surprisingly poor identification of at-risk infants, while gestational age performs well. Similar results in two countries that differ in mean birthweight, percent preterm, and neonatal mortality suggest robustness across populations.

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.

Term Birth Weight and Neurodevelopmental Outcomes.

BACKGROUND: Preterm birth is an important risk factor for neurodevelopmental disabilities. The vast majority of these disabilities occur, however, among term births. The role of fetal growth restriction specifically among term babies has been incompletely described. METHODS: We conducted a population-based study of term birth weight and its link to a range of neurodevelopmental outcomes using Norwegian health registries. To remove the influence of preterm birth, we restricted our analyses to 1.8 million singleton babies born during a narrow range of term gestational age (39-41 weeks). Babies with malformations were excluded. We adjusted analyses simply for year of birth, as further adjustments for sex, parity, maternal age, smoking, marital status, immigrant status, and parental education had trivial influence. An additional sibling analysis controlled for unmeasured family-based confounding. RESULTS: The risk of neurodevelopmental disabilities at term steadily increased at birth weights lower than 3.5 kg. Using the category of 3.5-3.9 kg as the reference, the odds reached 25-fold for cerebral palsy at the smallest weights (95% confidence interval 8.0, 79), 16-fold for vision/hearing disability (4.0, 65), 11-fold for intellectual impairment (6.9, 17), 7-fold for schizophrenia (1.0, 50), 5.4-fold for epilepsy (2.6, 12), and 3.5-fold for autism spectrum (1.3, 9.4) and behavioral disorders including attention-deficit hyperactivity disorder (2.1, 5.4). Associations remained robust with sibling controls. CONCLUSIONS: Reduced fetal growth is a powerful predictor of a wide variety of neurodevelopmental disabilities independent of preterm delivery.

Maternal Chronic Conditions and Risk of Cerebral Palsy in Offspring: A National Cohort Study.

BACKGROUND AND OBJECTIVES: Previous studies suggest that children of mothers with certain chronic conditions may be at increased risk of cerebral palsy (CP). We explored possible associations between 17 maternal chronic conditions and CP in offspring. METHODS: We conducted a prospective cohort study of Norwegian children born in 1990-2012 and surviving to 2 years of age. Information on maternal chronic conditions during pregnancy were extracted from the Medical Birth Registry of Norway (1990-2012). Information on chronic conditions in mothers and fathers recorded in the Norwegian Patient Registry (2008-2014) was available for a subset of children. CP diagnoses were extracted from the National Insurance Scheme (1990-2014) and the Norwegian Patient Registry (2008-2014). We estimated relative risks (RRs) and 95% confidence intervals (CIs) of CP in offspring of parents with chronic conditions compared with the general population using log binominal regression models. RESULTS: A total of 1 360 149 Norwegian children, including 3575 children with CP (2.6 per 1000 live births), fulfilled the inclusion criteria. The highest risk of CP was among offspring of mothers with type 2 diabetes (RR 3.2; 95% CI 1.8-5.4), lupus erythematosus (RR 2.7; 95% CI 0.9-8.3), type 1 diabetes (RR 2.2; 95% CI 1.4-3.4), and Crohn disease (RR 2.1; 95% CI 1.0-4.1) during pregnancy. No increased risks were seen for offspring of fathers with chronic conditions. CONCLUSIONS: Several maternal chronic conditions were associated with increased risk of CP in offspring. Maternal autoimmune disorders carried a particular risk.

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.

Country of first birth and neonatal outcomes in migrant and Norwegian-born parous women in Norway: a population-based study.

BACKGROUND: This study compares subsequent birth outcomes in migrant women who had already had a child before arriving in Norway with those in migrant women whose first birth occurred in Norway. The aim of this study was to investigate the associations between country of first birth and adverse neonatal outcomes (very preterm birth, moderately preterm birth, post-term birth, small for gestational age, large for gestational age, low Apgar score, stillbirth and neonatal death) in parous migrant and Norwegian-born women. METHODS: National population-based study including second and subsequent singleton births in Norway from 1990 to 2016. Data were retrieved from the Medical Birth Registry of Norway and Statistics Norway. Neonatal outcomes were compared between births to: 1) migrant women with a first birth before immigration to Norway (n = 30,062) versus those with a first birth after immigration (n = 66,006), and 2) Norwegian-born women with a first birth outside Norway (n = 6205) versus those with a first birth in Norway (n = 514,799). Associations were estimated as crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using multiple logistic regression. RESULTS: Migrant women with a first birth before immigrating to Norway had increased odds of adverse outcomes in subsequent births relative to those with a first birth after immigration: very preterm birth (22-31 gestational weeks; aOR = 1.27; CI 1.09-1.48), moderately preterm birth (32-36 gestational weeks; aOR = 1.10; CI 1.02-1.18), post-term birth (≥42 gestational weeks; aOR = 1.19; CI 1.11-1.27), low Apgar score (< 7 at 5 min; aOR = 1.27; CI 1.16-1.39) and stillbirth (aOR = 1.29; CI 1.05-1.58). Similar results were found in the sample of births to Norwegian-born women. CONCLUSIONS: The increased odds of adverse neonatal outcomes for migrant and Norwegian-born women who had their first births outside Norway should serve as a reminder of the importance of taking a careful obstetric history in these parous women to ensure appropriate care for their subsequent pregnancies and births in Norway.

Association of Preeclampsia in Term Births With Neurodevelopmental Disorders in Offspring.

Importance: Preeclampsia during pregnancy has been linked to an increased risk of cerebral palsy in offspring. Less is known about the role of preeclampsia in other neurodevelopmental disorders. Objective: To determine the association between preeclampsia and a range of adverse neurodevelopmental outcomes in offspring after excluding preterm births. Design, Setting, and Participants: This prospective, population-based cohort study included singleton children born at term from January 1, 1991, through December 31, 2009, and followed up through December 31, 2014 (to 5 years of age), using Norway's Medical Birth Registry and linked to other demographic, social, and health information by Statistics Norway. Data were analyzed from May 30, 2018, to November 17, 2019. Exposures: Maternal preeclampsia. Main Outcomes and Measures: Associations between preeclampsia in term pregnancies and cerebral palsy, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, intellectual disability, and vision or hearing loss using multivariable logistic regression. Results: The cohort consisted of 980 560 children born at term (48.8% female and 51.2% male; mean [SD] gestational age, 39.8 [1.4] weeks) with a mean (SD) follow-up of 14.0 (5.6) years. Among these children, 28 068 (2.9%) were exposed to preeclampsia. Exposed children were at increased risk of ADHD (adjusted odds ratio [OR], 1.18; 95% CI, 1.05-1.33), ASD (adjusted OR, 1.29; 95% CI, 1.08-1.54), epilepsy (adjusted OR, 1.50; 95% CI, 1.16-1.93), and intellectual disability (adjusted OR, 1.50; 95% CI, 1.13-1.97); there was also an apparent association between preeclampsia exposure and cerebral palsy (adjusted OR, 1.30; 95% CI, 0.94-1.80). Conclusions and Relevance: Preeclampsia is a well-established threat to the mother. Other than the hazards associated with preterm delivery, the risks to offspring from preeclampsia are usually regarded as less important. This study's findings suggest that preeclampsia at term may have lasting effects on neurodevelopment of the child.

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. WHAT THIS PAPER ADDS: Children of higher-educated parents had significantly lower odds of cerebral palsy (CP). There was no evidence of difference in risk of CP within first cousins whose mothers or fathers had different educational levels. Association between parental education and odds of CP did not reflect a causal effect.

Isolated single umbilical artery and the risk of adverse perinatal outcome and third stage of labor complications: A population-based study.

INTRODUCTION: Isolated single umbilical artery (iSUA) refers to single umbilical artery cords with no other fetal malformations. The association of iSUA to adverse outcome of pregnancy has not been consistently reported, and whether iSUA carries increased risk of third stage of labor complications has not been studied. We aimed to investigate the risk of adverse perinatal outcome, third stage of labor complications, and associated placental and cord characteristics in pregnancies with iSUA. A further aim was to assess the risk of recurrence of iSUA and anomalous cord or placenta characteristics in Norway. MATERIAL AND METHODS: This was a population-based study of all singleton pregnancies with gestational age >16 weeks at birth using data from the Medical Birth Registry of Norway from 1999 to 2014 (n = 918 933). Odds ratios (OR) with 95% confidence intervals were calculated for adverse perinatal outcome (preterm birth, perinatal and intrauterine death, low Apgar score, transferral to neonatal intensive care ward, placental and cord characteristics [placental weight, cord length and knots, anomalous cord insertion, placental abruption and previa]), and third stage of labor complications (postpartum hemorrhage and the need for manual placental removal or curettage) in pregnancies with iSUA, and recurrence of iSUA using generalized estimating equations and logistic regression. RESULTS: Pregnancies with iSUA carried increased risk of adverse perinatal outcome (OR 5.06, 95% confidence interval [CI] 4.26-6.02) and perinatal and intrauterine death (OR 5.62, 95% CI 4.69-6.73), and a 73% and 55% increased risk of preterm birth and small-for-gestational-age neonate, respectively. The presence of iSUA also carried increased risk of a small placenta, placenta previa and abruption, anomalous cord insertion, long cord, cord knot and third stage of labor complications. Women with iSUA, long cord or anomalous cord insertion in one pregnancy carried increased risk of iSUA in the subsequent pregnancy. CONCLUSIONS: The presence of ISUA was associated with a more than five times increased risk of intrauterine and perinatal death and with placental and cord complications. The high associated risk of adverse outcome justifies follow up with assessment of fetal wellbeing in the third trimester, intrapartum surveillance and preparedness for third stage of labor complications.

Stillbirth in relation to maternal country of birth and other migration related factors: a population-based study in Norway.

BACKGROUND: Migrant women's overall increased risk of adverse pregnancy outcomes is well known. The aim of this study was to investigate possible associations between stillbirth and maternal country of birth and other migration related factors (paternal origin, reason for immigration, length of residence and birthplace of firstborn child) in migrant women in Norway. METHODS: Nationwide population-based study including births to primiparous and multiparous migrant women (n = 198,520) and non-migrant women (n = 1,156,444) in Norway between 1990 and 2013. Data from the Medical Birth Registry of Norway and Statistics Norway. Associations were investigated by multiple logistic regression and reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Primiparous women from Sri-Lanka and Pakistan, and multiparous women from Pakistan, Somalia, the Philippines and Former Yugoslavia had higher odds of stillbirth when compared to non-migrant women (adjusted OR ranged from 1.58 to 1.79 in primiparous and 1.50 to 1.71 in multiparous women). Primiparous migrant women whose babies were registered with Norwegian-born fathers had decreased odds of stillbirth compared to migrant women whose babies were registered with foreign-born fathers (aOR = 0.73; CI 0.58-0.93). Primiparous women migrating for work or education had decreased odds of stillbirth compared to Nordic migrants (aOR = 0.58; CI 0.39-0.88). Multiparous migrant women who had given birth to their first child before arriving in Norway had higher odds of stillbirth in later births in Norway compared with multiparous migrant women who had their first child after arrival (aOR = 1.28; CI 1.06-1.55). Stillbirth was not associated with length of residence in Norway. CONCLUSIONS: This study identifies sub-groups of migrant women who are at an increased risk of stillbirth, and highlights the need to improve care for them. More attention should be paid to women from certain countries, multiparous women who had their first baby before arrival and primiparous women whose babies have foreign-born fathers.

Preeclampsia by maternal reasons for immigration: a population-based study.

BACKGROUND: To investigate whether the occurrence of preeclampsia varied by maternal reasons for immigration. METHODS: We included 1,287,270 singleton pregnancies (163,508 to immigrant women) in Norway during 1990-2013. Individual data were obtained through record linkage between the Medical Birth Registry of Norway and Statistics Norway. Analyses were performed for preeclampsia overall and in combination with preterm birth < 37 and < 34 weeks of gestation, referred to as preterm and very preterm preeclampsia. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression with robust standard errors, adjusted for relevant covariates, including maternal income and education. RESULTS: Preeclampsia was reported in 3.5% of Norwegian women and 2.5% of immigrants. Compared with Norwegian women, the adjusted OR for preeclampsia was lowest in labour immigrants (adjusted OR 0.55 [95% CI 0.49-0.62]), followed by family immigrants (0.62 [0.59-0.65]), immigrant students (0.75 [0.65-0.86]), refugees (0.81 [0.75-0.88]), and immigrants from other Nordic countries (0.87 [0.80-0.94]). Compared with Norwegian women, labour immigrants also had lower adjusted odds of preterm and very preterm preeclampsia, whereas refugees had increased adjusted odds of preterm and very preterm preeclampsia (< 37 weeks: 1.18 [1.02-1.36], and < 34 weeks: 1.41 [1.15-1.72]). CONCLUSIONS: The occurrence of preeclampsia was lower overall in immigrants than in non-immigrants, but associations varied by maternal reasons for immigration. Maternity caregivers should pay increased attention to pregnant women with refugee backgrounds due to their excess odds of preterm preeclampsia.

Parental socioeconomic status and risk of cerebral palsy in the child: evidence from two Nordic population-based cohorts.

Background: We investigated whether the risk of cerebral palsy (CP) in the child varies by parents' socioeconomic status, in Denmark and Norway. Methods: We included almost 1.3 million children born in Demark during 1981-2007 and 2.4 million children born in Norway during 1967-2007, registered in the Medical Birth registries. Data on births were linked to Statistics Denmark and Norway to retrieve information on parents' education and relationship status and, in Denmark, also income. CP diagnoses were obtained from linkage with national registries. We used multivariate log-binominal regression models to estimate relative risk (RR) of CP according to parental socioeconomic status. Results: There was a strong trend of decreasing risk of CP with additional education of both the mother and the father. These trends were nearly identical for the two parents, with a one-third reduction in risk for those with the highest education compared with parents with the lowest education. When both parents had high education, risk of CP was further reduced (RR 0.58, 0.53-0.63). Women with partners had a reduction in risk (RR 0.79, 0.74-0.85) compared with single mothers overall. Risk patterns were stable over time, across countries and within spastic bilateral and unilateral CP. Household income was not associated with risk of CP. Conclusions: Risk of CP in two Scandinavian countries was lower among educated parents and mothers with a partner, but unrelated to income. Factors underlying this stable association with education are unknown, but could include differences in potentially modifiable lifestyle factors and health behaviours.

Preterm Children Have Higher Risk Than Full-term Children of Invasive Pneumococcal Disease During the First 2 Years of Life.

BACKGROUND: A few previous studies have reported an increased risk of invasive pneumococcal disease (IPD) in children born preterm, but this has not been investigated in a cohort study. The impact of 7-valent pneumococcal conjugate vaccine (PCV7) on IPD incidence rates in preterm children is unknown. METHODS: Data from the Medical Birth Registry of Norway (2002-2010) were linked to other national registries. In total, 628,138 children were included in our study and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated with Poisson regression. RESULTS: We identified 411 cases of IPD. We observed higher rates of IPD in preterm than in full-term children for the intervals 0-23, 0-5 and 6-23 months of age, IRRs = 1.83 (95 % CI: 1.36-2.47), 2.95 (95% CI: 1.44-6.06) and 1.69 (95% CI: 1.22-2.34), respectively. The risk for IPD was reduced in the PCV7-period (2007-2010) compared with that of the pre PCV7-period (2002-2005) for children 6-23 months of age, IRRs = 0.20 (95% CI: 0.08-0.53) for preterm children and 0.28 (95% CI: 0.21-0.38) for full-term children, but not for those 0-5 months of age, IRRs = 1.94 (95% CI: 0.48-7.80) and 0.71 (95% CI: 0.38-1.33). CONCLUSIONS: Preterm children had an increased risk of IPD. After introduction of PCV7, the rate of IPD was reduced among preterm and full-term children from 6 months of age.