Association of placental and umbilical cord characteristics with cerebral palsy: national cohort study.

OBJECTIVES: Cerebral palsy (CP) is a group of movement disorders usually diagnosed in childhood. A substantial proportion are thought to be caused by antenatal events. Abnormalities of the umbilical cord and placenta are associated with an increased risk of adverse neonatal outcomes, but it is unclear whether these conditions also carry an increased risk of CP. We aimed to determine whether abnormalities of the umbilical cord or placenta are associated with CP and assess if these associations differ by sex of the child or gestational age at birth. METHODS: We performed a national cohort study by linking data from The Medical Birth Registry of Norway with other national registries. All liveborn singletons born between 1999 and 2017 (n = 1 087 486) were included and followed up until the end of 2019. Diagnoses of CP were provided by the Norwegian National Insurance Scheme and the Norwegian Patient Register. We used generalized estimating equations and multilevel log binomial regression to calculate relative risks (RR), adjusted for year of birth, and stratified analyses were carried out based on sex and gestational age at birth. Exposures were abnormal umbilical cord (velamentous or marginal insertion, single umbilical artery (SUA), knots and entanglement), and placental abnormalities (retained placenta, placental abruption and previa). RESULTS: A total of 2443 cases with CP (59.8% males) were identified. Velamentous cord insertion (adjusted RR (aRR), 2.11 (95% CI, 1.65-2.60)), cord knots (aRR, 1.53 (95% CI, 1.15-2.04)) and placental abnormalities (placenta previa (aRR, 3.03 (95% CI, 2.00-4.61)), placental abruption (aRR, 10.63 (95% CI, 8.57-13.18)) and retained placenta (aRR, 1.71 (95% CI, 1.32-2.22))) carried an increased risk of CP. Velamentous cord insertion was associated with CP regardless of gestational age or sex. A retained placenta was associated with a 2-fold increased risk for CP in males, while the associations of SUA and cord knot with CP were significant only among females. CONCLUSIONS: The detection of placental and umbilical cord abnormalities may help identify children at increased risk of CP. The associations between placental or umbilical cord abnormalities and the risk of CP do not vary substantially with gestational age at birth or sex of the child. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Single umbilical artery and risk of congenital malformation: 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. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Reproduction and marriage among male survivors of cancer in childhood, adolescence and young adulthood: a national cohort study.

BACKGROUND: Increased survival after cancer in young age has made long-term follow-up studies of high external validity important. In this national cohort study, we explored the impact of cancer in young age on reproduction and marital status in male survivors. METHODS: Hazard ratios (HRs) and relative risks (RRs) of reproductive and marital outcomes were studied for male survivors of cancer in young age (<25 years) and cancer-free male comparisons, born during 1965-1985, by linking compulsory national registries in Norway. RESULTS: Male cancer survivors (n=2687) had reduced paternity (HR: 0.72, 95% confidence interval (CI): 0.68-0.76). This was most apparent in survivors of testicular cancer, brain tumours, lymphoma, leukemia and bone tumours, and when diagnosed with cancer before 15 years of age. Male cancer survivors were more likely to avail of assisted reproduction (RR: 3.32, 95% CI: 2.68-4.11). There was no increased risk of perinatal death, congenital malformations, being small for gestational age, of low birth weight or preterm birth in their first offspring. Male cancer survivors were less likely to marry (HR: 0.93, 95% CI: 0.86-1.00), in particular brain tumour survivors. CONCLUSIONS: In this national cohort study, we demonstrated reduced paternity and increased use of assisted reproduction among male cancer survivors, but no adverse outcome for their first offspring at birth.

Intrapartum monitoring with cardiotocography and ST-waveform analysis in breech presentation: an observational study.

OBJECTIVE: To determine the electrocardiographic performance and neonatal outcome of pregnancies with breech presentation and planned vaginal delivery monitored with ST-waveform analysis (STAN). DESIGN: Prospective observational study. SETTING: University hospital, Norway; 2004-2008. POPULATION: Singleton pregnancies with a gestational age above 35 + 6 weeks, breech presentation, selected for vaginal delivery and monitored with STAN. METHODS: Common clinical guidelines for STAN monitoring were used. An experienced neonatologist graded the symptoms of neonatal encephalopathy. The outcome was compared with STAN-monitored high-risk deliveries in a vertex presentation (n = 5569) using logistic regression analysis. MAIN OUTCOME MEASURE: Frequency of ST events, indications of intervention for fetal distress, and neonatal morbidity and mortality. RESULTS: Breech presentation occurred in 750 of 23,219 (3.2%) deliveries, 625 (83%) of which were selected for vaginal delivery. Intrapartum monitoring by STAN was performed in 433 (69%). Compared with vertex presentations, fetuses in breech presentation had a lower risk of baseline T/QRS rise during labour [odds ratio (OR) = 0.7, 95% confidence interval (95% CI) = 0.7-0.9, P = 0.003] and a higher risk for intervention as a result of preterminal cardiotocogram (OR = 2.9, 95% CI = 1.6-5.9, P = 0.001). The risks of perinatal mortality (OR = 1.8, 95% CI = 0.2-15, P = 0.6), cord metabolic acidosis (OR = 0.8, 95% CI = 0.2-3.2, P = 0.7) and moderate or severe neonatal encephalopathy (OR = 1.8, 95% CI = 0.5-6.2, P = 0.3) did not differ significantly between breech and vertex deliveries. CONCLUSION: STAN can be used for the surveillance of breech presentations selected for vaginal delivery with an acceptable neonatal outcome. The electrocardiogram (ECG) pattern during labour varies with the fetal presentation.

Maternal hormonal contraceptive use and offspring overweight or obesity.

BACKGROUND/OBJECTIVES: Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. SUBJECTS/METHODS: Using data from a large, prospective pregnancy cohort study (n=19 652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 to >4 months before (n=3392), 4 to >1 months before (n=2541), 1 to >0 months before (n=2997) and 0-12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. RESULTS: We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted odds ratio (OR): 0.75, 95% confidence interval (CI): 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between the use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. CONCLUSIONS: Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects.

Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study.

BACKGROUND: As the number of cancer survivors increases, their health and welfare have come into focus. Thus, long-term medical consequences of cancer at a young age (<25 years), obtained from social security benefit records, were studied. METHODS: Standardised incidence ratios (SIRs) of long-term medical consequences for 5-year cancer survivors, born during 1965-1985, were explored by linking population-based registries in Norway. RESULTS: Among the 5-year cancer survivors (4031 individuals), 29.7% received social security benefits. The survivors had an overall 4.4 times (95% confidence interval (95% CI): 4.1-4.6) higher risk of social security benefit uptake than the cancer-free population. Survivors of malignancies of bone and connective tissues (SIR: 10.8; 95% CI: 9.1-12.9), CNS tumours (SIR: 7.7; 95% CI: 6.9-8.6) and malignancies of the haematopoietic system (SIR: 6.1; 95% CI: 5.3-7.0) had the highest risks of social security benefits uptake. The most notified causes of social security benefit uptake were diseases of the nervous system, and injury and poisoning. CONCLUSION: The uptake of social security benefits among 5-year cancer survivors increased substantially and it may represent a solid outcome measure for the burden of the most severe late effects, especially in countries with comparable social welfare systems.

Degree of fetal growth restriction associated with schizophrenia risk in a national cohort.

BACKGROUND: Accumulating evidence suggests that fetal growth restriction may increase risk of later schizophrenia but this issue has not been addressed directly in previous studies. We examined whether the degree of fetal growth restriction was linearly related to risk of schizophrenia, and also whether maternal pre-eclampsia, associated with both placental dysfunction and poor fetal growth, was related to risk of schizophrenia. METHOD: A population-based cohort of single live births in the Medical Birth Registry of Norway (MBRN) between 1967 and 1982 was followed to adulthood (n=873 612). The outcome was schizophrenia (n=2207) registered in the National Insurance Scheme (NIS). The degree of growth restriction was assessed by computing sex-specific z scores (standard deviation units) of ' birth weight for gestational age' and ' birth length for gestational age'. Analyses were adjusted for potential confounders. Maternal pre-eclampsia was recorded in the Medical Birth Registry by midwives or obstetricians using strictly defined criteria. RESULTS: The odds ratio (OR) for schizophrenia increased linearly with decreasing birth weight for gestational age z scores (p value for trend=0.005). Compared with the reference group (z scores 0.01­1.00), the adjusted OR [95% confidence interval (CI)] for the lowest z-score category (

Early severe weight loss in newborns after discharge from regular nurseries.

AIMS: To study incidence and risk factors of early neonatal dehydration in a Norwegian population based cohort. METHODS: Term neonates admitted to a paediatric department during 2002-2008 with a weight loss > or = 12% within three weeks of age were identified retrospectively through review of medical records. For each patient a sex-matched control group of two full-term infants was selected to assess risk factors for dehydration. RESULTS: A total of 38 of 37 321 infants (1.0 per thousand) were admitted at a median age of 6 (interquartile range 5-12) days, and the admission rate increased during the study period (p for trend = 0.008). Simultaneously, mean nursery stay decreased from 3.5 to 2.7 days (p = 0.022). Mean weight loss was 15.0% of birth weight and 17 of 29 (58.6%) had serum sodium above 145 mmol/L. The only significant difference between patients and controls was that mothers of patients were older (32.3 +/- 5.0 vs. 29.4 +/- 5.4 years, p = 0.005). CONCLUSION: Short nursery stay may be a risk factor for dehydration in newborn infants.

Joint association of Apgar scores and early neonatal symptoms with minor disabilities at school age.

OBJECTIVE: To examine whether the combination of a low five minute Apgar score and symptoms of neonatal encephalopathy is associated with minor impairments at school age. DESIGN: Population based cohort study. SETTING: Norway. PARTICIPANTS: All 727 children of the cohort were born between 1983 and 1987, had normal birth weights, no congenital malformations, and no major neurological abnormalities. The cohort comprised three groups with five minute Apgar scores of 0-3, 4-6, and 7-10, and were followed from birth to 8-13 years of age by combining data from The Medical Birth Registry, questionnaires, hospital discharge summaries, and the National Insurance Scheme. MAIN OUTCOME MEASURE: Neurodevelopmental impairments such as learning, behavioural, and minor motor difficulties. RESULTS: Children with a five minute Apgar score of 3 or less and signs consistent with neonatal encephalopathy had a significantly increased risk of developing minor motor impairments (odds ratio (OR) 12.8, 95% confidence interval (CI) 2.6 to 63.2), epilepsy (OR 7.0, 95% CI 1.3 to 39.2), need of extra resources in kindergarten (OR 7.0, 95% CI 1.3 to 39.2) or at school (OR 3.4, 95% CI 1.8 to 6.3), and had reduced performance in reading (OR 4.6, 95% CI 2.3 to 9.5) and mathematics (OR 3.3, 95% CI 1.5 to 7.3), compared with children with normal Apgar scores and no neonatal symptoms. They also more often had problems related to tractability, aggressivity, passivity, anxiety, academic performance, and fine motor development. CONCLUSION: Children with low Apgar scores and subsequent signs of cerebral depression who do not develop cerebral palsy may still have an increased risk of developing a variety of neurodevelopmental impairments and learning difficulties.

Neonatal mortality rates in communities with small maternity units compared with those having larger maternity units.

OBJECTIVE: To compare neonatal mortality in geographical areas where most deliveries occur in large hospitals with areas where a larger proportion of deliveries occur in small maternity units. DESIGN: Population-based study using data from The Norwegian Medical Birth Registry. SETTING: Records on all deliveries in Norway from 1967 to 1996, a total of 1.7 million births, were equipped with data on the size of the maternity units used by delivering women in that particular area. MAIN OUTCOME MEASURE: Risk of neonatal death. RESULTS: Women living in areas where the most frequently used delivery unit had less than 2000 annual deliveries had 1.2 fold the risk of experiencing neonatal death of their newborn (95% CI 1.1-1.3). The relative risk of neonatal death in geographical areas where more than 75% of deliveries occurred in units with more than 3000 annual births was 0.8 (95% CI 0.7-0.9) compared with areas where none delivered in such large units. The relative risk of neonatal death in areas where the most frequently used delivery units had less than 100 annual births was 1.4 (95% CI 1.1-1.7) compared with areas where units of more than 3000 annual births were the most frequently used. Differences in outcome could not be explained by differences in travelling distance to an urban centre where most referral delivery units are located, differences between rural and urban municipalities, or by differences in biological or socio-economic risk factors between municipalities. CONCLUSIONS: We observed a small but significantly decreased neonatal mortality in areas where the great majority of births occurred in large hospitals.

The association of Apgar score with subsequent death and cerebral palsy: A population-based study in term infants.

OBJECTIVE: To estimate the risk of adverse outcomes for newborns with a low Apgar score. STUDY DESIGN: Population-based cohort study. All 235,165 children born between 1983 and 1987 in Norway with a birth weight of at least 2500 g and no registered birth defects were followed up from birth to age 8 to 12 years by linkage of 3 national registries. Outcomes were death and cerebral palsy (CP). RESULTS: Five-minute Apgar scores of 0 to 3 were recorded for 0.1%, and scores of 4 to 6 were recorded for 0.6% of the children. Compared with children who had 5-minute Apgar scores of 7 to 10, children who had scores of 0 to 3 had a 386-fold increased risk for neonatal death (95% CI: 270-552) and an 81-fold (48-138) increased risk for CP. If Apgar scores at both 1 and 5 minutes were 0 to 3, the risks for neonatal death and CP were increased 642-fold (442-934) and 145-fold (85-248), respectively, compared with scores of 7 to 10. CONCLUSION: The strong association of low Apgar scores with death and CP in this population with a low occurrence of low scores shows that the Apgar score remains important for the early identification of infants at increased risk for serious and fatal conditions.

Assessing quality of obstetric care for low-risk deliveries; methodological problems in the use of population based mortality data.

BACKGROUND: Studies evaluating safety of different birth settings for low-risk deliveries are often difficult to interpret because of great methodological problems. OBJECTIVE: To assess potential bias in comparisons of mortality between maternity institutions with different size and level of care, particularly when using various definitions of low-risk delivery and when studying stillbirth rates. DESIGN: Population-based study. POPULATION: The population of 1.74 million births in Norway from 1967 to 1996 recorded in The Medical Birth Registry of Norway. METHODS: First we explored the problems of properly identifying low-risk deliveries from population-based data and calculated adjusted perinatal mortality rates in sub-populations by excluding different risk factors. Then we measured the difference in apparent low-risk deliveries between institutions of different size and level of care. Finally we explored bias by using stillbirths and discuss the loss of statistical power by studying only livebirths. RESULTS: The occurrence of a whole spectrum of risk factors differed between small and large institutions, even after adjustment for birthweight. Although the majority of births were from low-risk deliveries, only 1/10th of all perinatal deaths occurred in this group after admission to a maternity unit. There was a systematic difference in the reporting of time of death for stillbirths between types of institutions; the rate of stillbirths occurring during delivery was higher among small institutions, while large institutions were more often uncertain in classifying time of death for stillbirths. CONCLUSIONS: Adjustments for a large number of different risk factors, large sample-sizes and caution in including stillbirth as outcome measure are needed when comparisons of safety between different sizes of delivery units are made for low-risk pregnancies.

Relation between size of delivery unit and neonatal death in low risk deliveries: population based study.

AIM: To examine risk of neonatal death after low risk pregnancies in relation to size of delivery units. METHODS: A population based study of live born singleton infants in Norway with birthweights of at least 2500 g was carried out. Antenatal risk factors were adjusted for. RESULTS: From 1972 to 1995, 1.25 million births fulfilled the criteria. The neonatal death rate was lowest for maternity units with 2001-3000 annual births and steadily increased with decreasing size of the maternity unit to around twice that for units with less than 100 births a year (odds ratio 2.1; 95 % confidence interval 1.6 to 2.8). Institutions with more than 3000 deliveries a year also had a higher rate (odds ratio 1.7; 95% CI 1.4 to 2.0), but analyses suggest that this rate is overestimated. CONCLUSION: Around 2000 to 3000 annual births are needed to reduce the risk of neonatal deaths after low risk deliveries.

[High-frequency oscillation in newborn infants. A promising therapeutic principle when respirator therapy is hazardous]. / Høgfrekvent oscillering av nyfødde. Eit lovande behandlingsprinsipp ved vanskeleg respiratorbehandling.

14 newborn infants were ventilated with oscillation because of severe respiratory distress syndrome (n = 3), pulmonary air leaks (n = 4), pulmonary hypoplasia (n = 4) or sepsis and pneumonia (n = 3). All but four of the infants were more easily stabilized by oscillation than by conventional ventilation. Four infants survived after 1-5 (mean three) days of oscillation, and none developed severe chronic lung disease. New commercial ventilators make this mode of ventilation of newborn infants relatively simple. Small premature babies who require high pressures with conventional ventilation, babies with pulmonary air leaks and babies with hypoplastic lungs may benefit from oscillation.

[Epidermolysis bullosa gravis Herlitz. A challenge for a pediatric department]. / Epidermolysis bullosa gravis Herlitz. En utfordring for en barneavdeling.

Epidermolysis bullosa is the collective name for a heterogeneous group of inherited disorders characterized by marked fragility of the skin and formation of blisters following minor trauma to the skin. The pediatric departments at Telemark County Hospital, in Porsgrunn, and at the University Clinic, Haukeland Hospital, have cared for two babies subclassified as having the Herlitz type of the disease. This type has a very poor prognosis. The article includes a brief description of the disease, discusses practical and ethical problems and challenges, and describes the departments' attempts to tackle them.