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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Suicide and violent deaths in survivors of cancer in childhood, adolescence and young adulthood-A national cohort study.

Suicide risk in adult cancer patients is found to be elevated, but limited information exists regarding risks of suicide and non-suicidal violent deaths when diagnosed with cancer in young age. We investigate suicide and violent deaths in a national cohort including individuals diagnosed with cancer before age 25. Through the linkage of different national registries (Cancer Registry of Norway, Norwegian Causes of Death Registry and the National Registry) a cohort of all live births in Norway during 1965-1985 was defined and followed up through 2008. Individuals diagnosed with cancer before age 25 and the cancer-free references were compared using an extended Cox proportional hazard regression model. The cohort comprised 1,218,013 individuals, including 5,440 diagnosed with cancer before age 25. We identified 24 suicides and 14 non-suicidal violent deaths in the cancer group. The hazard ratio (HR) of suicide in the cancer group was 2.5 (95% confidence interval (CI) 1.7-3.8), and was increased both when diagnosed with cancer in childhood (0-14 years of age); HR = 2.3 (95% CI: 1.2-4.6), and during adolescence/young adulthood (15-24 years); HR = 2.6 (95% CI: 1.5-4.2). Survivors of bone/soft tissue sarcomas, CNS tumors and testicular cancer were at particular risk. The risk of non-suicidal violent death was not increased in the cancer survivors (HR = 1.0; 95% CI: 0.6-1.7). Although based on small numbers and the absolute risk of suicide being low, these are novel findings with important implications for establishing adequate follow-up including suicide prevention strategies for young cancer survivors.

Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up.

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

Economic independence in survivors of cancer diagnosed at a young age: A Norwegian national cohort study.

BACKGROUND: The impact of cancer on socioeconomic outcomes is attracting attention as the number of survivors of cancer in young age continues to rise. This study examines economic independence in a national cohort of survivors of cancer at a young age in Norway. METHODS: Through the linkage of several national registries, the study cohort comprised 1,212,013 individuals born in Norway during 1965 through 1985, of which 5440 had received a cancer diagnosis before age 25 years. Follow-up was through 2007, and the main outcomes were receipt of governmental financial assistance, employment, income, and occupation. Analytic methods included Cox proportional hazard regression, log-binomial regression, and quantile regression models. RESULTS: Individuals in the cancer survivor group had an increased probability of receiving governmental financial assistance (men: hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.3-1.5; women: HR, 1.5; 95% CI, 1.3-1.6) and of not being employed (men: HR, 1.4; 95% CI, 1.2-1.7; women: HR, 1.4; 95% CI, 1.2-1.6) compared with those in the noncancer group. Income discrepancies were particularly pronounced for survivors of central nervous system tumors. There was no difference in representation in higher skilled occupations. CONCLUSIONS: Survivors of cancer at a young age in Norway had an increased risk of being economically dependent and unemployed. This was evident in several tumor groups and was most pronounced in female survivors. There were only small differences in income or representation in higher skilled occupations for most employed survivors compared with the noncancer group. The current results are important for understanding the impact of a cancer diagnosis at a young age on subsequent job market outcomes. Cancer 2016;122:3873-3882. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study.

BACKGROUND: Postnatal administration of caffeine may reduce the risk of cerebral palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal caffeine exposure remains unknown. OBJECTIVE: We investigated the association of intake of caffeine by pregnant women and risk of CP in their children. METHODS: The study was based on The Norwegian Mother and Child Cohort Study, comprising >100,000 live-born children, of whom 222 were subsequently diagnosed with CP. Mothers reported their caffeine consumption in questionnaires completed around pregnancy week 17 (102,986 mother-child pairs), week 22 (87,987 mother-child pairs), and week 30 (94,372 mother-child pairs). At week 17, participants were asked about present and prepregnancy consumption. We used Cox regression models to estimate associations between exposure [daily servings (1 serving = 125 mL) of caffeinated coffee, tea, and soft drinks and total caffeine consumption] and CP in children, with nonconsumers as the reference group. Models included adjustment for maternal age and education, medically assisted reproduction, and smoking, and for each source of caffeine, adjustments were made for the other sources. RESULTS: Total daily caffeine intake before and during pregnancy was not associated with CP risk. High consumption (≥6 servings/d) of caffeinated soft drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95% CI: 1.2, 3.1), and children of women consuming 3-5 daily servings of caffeinated soft drinks during pregnancy weeks 13-30 also had an increased CP risk (HR: 1.7; 95% CI: 1.1, 2.8). A mean daily consumption of 51-100 mg caffeine from soft drinks during the first half of pregnancy was associated with a 1.9-fold increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6). CONCLUSIONS: Maternal total daily caffeine consumption before and during pregnancy was not associated with CP risk in children. The observed increased risk with caffeinated soft drinks warrants further investigation.

Associations of maternal atopic diseases with adverse pregnancy outcomes: a national cohort study.

BACKGROUND: Maternal asthma has been associated with adverse pregnancy outcomes. Little is known about the influence of other atopic diseases on pregnancy outcomes. We assessed how various maternal atopic diseases might affect preterm birth, stillbirth, and neonatal death. METHODS: By linking Norwegian national registries, we acquired information on maternal health, socio-demographic factors, pregnancy, birth, and neonatal outcome on all births in Norway from 1967 to 2003. RESULTS: A total of 1 974 226 births were included. Of these, 1.8% had a record of maternal asthma, 3.4% of maternal atopic dermatitis, and 0.4% of maternal allergic rhinoconjunctivitis. Overall rates of preterm birth, stillbirth, and neonatal death were 6.0%, 0.6%, and 0.5%, respectively. After adjustments for possible confounders, maternal asthma was associated with increased risk of preterm birth (relative risk (RR), 1.15, [95% confidence interval (CI) 1.10, 1.21]). In contrast, maternal atopic dermatitis was associated with decreased risk of preterm birth (RR 0.90, [95% CI 0.86, 0.93]), stillbirth (RR 0.70, [95% CI 0.62, 0.79]), and neonatal death (RR 0.76, [95% CI 0.65, 0.90]). Similarly, maternal allergic rhinoconjunctivitis was associated with decreased risk of preterm birth (RR 0.84, [95% CI 0.76, 0.94]) and stillbirth (RR 0.40, [95% CI 0.25, 0.66]). CONCLUSIONS: We confirmed the previously reported association of maternal asthma with increased risk for preterm birth. Unexpectedly, maternal atopic dermatitis and allergic rhinoconjunctivitis were associated with decreased risk of preterm birth and stillbirth. Mechanisms for these protective associations are unclear, and our findings require confirmation in further studies.

Risk of cerebral palsy in relation to pregnancy disorders and preterm birth: a national cohort study.

AIM: To assess the risk of developing cerebral palsy in relation to pregnancy disorders and preterm birth. METHOD: By linking the Medical Birth Registry of Norway to other national registries, we identified all live births in Norway from 1967 through to 2001. Risks of cerebral palsy (CP) after preterm delivery and pregnancy disorders were estimated in different gestational age groups. RESULT: In total, 1 764 509 children delivered at 23 to 43 weeks' gestation were included. The prevalence of CP was 1.8 per 1000 births. Absolute risk of CP was 8.5% among children born at 23 to 27 weeks' gestation, 5.6% at 28 to 30 weeks, 2.0% at 31 to 33 weeks, 0.4% at 34 to 36 weeks, and 0.1% thereafter. Placental abruption, chorioamnionitis, prolonged rupture of membranes, intrauterine growth restriction, pre-eclampsia, multiple births, placenta previa, bleeding, cervical conization, and congenital malformation were all associated with CP. Before 32 weeks' gestation, absolute risk of CP was highest with chorioamnionitis (9.1%) and lowest with pre-eclampsia (3.1%). Among those born after 31 weeks, the absolute risk of CP was more consistently (but also more slightly) increased with a recorded pregnancy disorder. INTERPRETATION: Early delivery and pregnancy disorders were both strong risk factors for CP. The added risks with recorded pregnancy disorders varied within categories of gestational age.