Perinatal mortality by gestational week and size at birth in singleton pregnancies at and beyond term: a nationwide population-based cohort study

Background: Whether gestational age per se increases perinatal mortality in post-term pregnancy is unclear. We aimed at assessing gestational week specific perinatal mortality in small-for-gestational-age (SGA) and non-SGA term and post-term gestations, and specifically to evaluate whether the relation between post-term gestation and perinatal mortality differed before and after ultrasound was introduced as the standard method of gestational age estimation. Methods: A population-based cohort study, using data from the Medical Birth Registry of Norway (MBRN), 1967–2006, was designed. Singleton births at 37 through 44 gestational weeks (n = 1 855 682), excluding preeclampsia, diabetes and fetal anomalies, were included. Odds ratios (OR) with 95% confidence intervals (CI) for perinatal mortality and stillbirth in SGA and non-SGA births by gestational week were calculated. Results: SGA infants judged post-term by LMP had significantly higher perinatal mortality than post-term non-SGA infants at 40 weeks, independent of time period (highest during 1999–2006 [OR 9.8, 95% CI: 5.7-17.0]). When comparing years before (1967–1986) versus after (1987–2006) ultrasound was introduced, there was no decrease in the excess mortality for post-term SGA versus non-SGA births (ORs from 6.1 [95% CI: 5.2-7.1] to 6.7 [5.2-8.5]), while mortality at 40 weeks decreased significantly (ORs from 4.6, [4.0-5.3] to 3.2 [2.5-3.9]). When assessing stillbirth risk (1999–2006), more than 40% of SGA stillbirths (11/26) judged to be ≥41 weeks by LMP were shifted to lower gestational ages using ultrasound estimation. Conclusions: Mortality risk in post-term infants was strongly associated with growth restriction. Such infants may erroneously be judged younger than they are when using ultrasound estimation, so that the routine assessment for fetal wellbeing in the prolonged gestation may be given too late

Perinatal mortality by gestational week and size at birth in singleton pregnancies at and beyond term: a nationwide population-based cohort study

BACKGROUND: Whether gestational age per se increases perinatal mortality in post-term pregnancy is unclear. We aimed at assessing gestational week specific perinatal mortality in small-for-gestational-age (SGA) and non-SGA term and post-term gestations, and specifically to evaluate whether the relation between post-term gestation and perinatal mortality differed before and after ultrasound was introduced as the standard method of gestational age estimation. METHODS: A population-based cohort study, using data from the Medical Birth Registry of Norway (MBRN), 1967–2006, was designed. Singleton births at 37 through 44 gestational weeks (n = 1 855 682), excluding preeclampsia, diabetes and fetal anomalies, were included. Odds ratios (OR) with 95% confidence intervals (CI) for perinatal mortality and stillbirth in SGA and non-SGA births by gestational week were calculated. RESULTS: SGA infants judged post-term by LMP had significantly higher perinatal mortality than post-term non-SGA infants at 40 weeks, independent of time period (highest during 1999–2006 [OR 9.8, 95% CI: 5.7-17.0]). When comparing years before (1967–1986) versus after (1987–2006) ultrasound was introduced, there was no decrease in the excess mortality for post-term SGA versus non-SGA births (ORs from 6.1 [95% CI: 5.2-7.1] to 6.7 [5.2-8.5]), while mortality at 40 weeks decreased significantly (ORs from 4.6, [4.0-5.3] to 3.2 [2.5-3.9]). When assessing stillbirth risk (1999–2006), more than 40% of SGA stillbirths (11/26) judged to be ≥41 weeks by LMP were shifted to lower gestational ages using ultrasound estimation. CONCLUSIONS: Mortality risk in post-term infants was strongly associated with growth restriction. Such infants may erroneously be judged younger than they are when using ultrasound estimation, so that the routine assessment for fetal wellbeing in the prolonged gestation may be given too late

Lipid levels after childbirth and association with number of children: A population-based cohort study

Objective Low parity women are at increased risk of cardiovascular mortality. Unfavourable lipid profiles have been found in one-child mothers years before they conceive. However, it remains unclear whether unfavourable lipid profiles are evident in these women also after their first birth. The aim was to estimate post-pregnancy lipid levels in one-child mothers compared to mothers with two or more children and to assess these lipid’s associations with number of children. Methods We used data on 32 618 parous women (4 490 one-child mothers and 28 128 women with ≥2 children) examined after first childbirth as part of Cohort of Norway (1994–2003) with linked data on reproduction and number of children from the Medical Birth Registry of Norway (1967–2008). Odds ratios (ORs) with 95% confidence intervals (CIs) for one lifetime pregnancy (vs. ≥2 pregnancies) by lipid quintiles were obtained by logistic regression and adjusted for age at examination, year of first birth, body mass index, oral contraceptive use, smoking and educational level. Results Compared to women with the lowest quintiles, ORs for one lifetime pregnancy for the highest quintiles of LDL and total cholesterol were 1.30 (95%CI: 1.14–1.45) and 1.43 (95%CI: 1.27–1.61), respectively. Sensitivity analysis (women <40 years) showed no appreciable change in our results. In stratified analyses, estimates were slightly stronger in overweight/obese, physically inactive and women with self-perceived bad health. Conclusions Mean lipid levels measured after childbirth in women with one child were significantly higher compared to mothers with two or more children and were associated with higher probability of having only one child. These findings corroborate an association between serum lipid levels and one lifetime pregnancy (as a feature of subfecundity), emphasizing that these particular women may be a specific predetermined risk group for cardiovascular related disease and death.publishedVersio

Women's prepregnancy lipid levels and number of children: a Norwegian prospective population-based cohort study

Objective. To study prepregnancy serum lipid levels and the association with the number of children. Design. Prospective, population-based cohort. Setting. Linked data from the Cohort of Norway and the Medical Birth Registry of Norway. Participants. 2645 women giving birth to their first child during 1994–2003 (488 one-child mothers and 2157 women with ≥2 births) and 1677 nulliparous women. Main outcome measures. ORs for no and one lifetime pregnancy (relative to ≥2 pregnancies) obtained by multinomial logistic regression, adjusted for age at examination, education, body mass index (BMI), smoking, time since last meal and oral contraceptive use. Results. Assessed in quintiles, higher prepregnant triglyceride (TG) and TG to high-density lipoprotein (TG:HDL-c) ratio levels were associated with increased risk of one lifetime pregnancy compared with having ≥2 children. Compared with the highest quintile, women in the lowest quintile of HDL cholesterol levels had an increased risk of one lifetime pregnancy (OR 1.7, 95% CI 1.2 to 2.4), as were women with the highest low-density lipoprotein (LDL) cholesterol, TG and TG:HDL-c ratio quintiles (compared with the lowest) (OR 1.2, 95% CI 0.8 to 1.7; OR 2.2, 95% CI 1.5 to 3.2; and OR 2.2, 95% CI 1.5 to 3.2, respectively). Similar effects were found in women with BMI≥25 and the highest LDL and total cholesterol levels in risk of lifetime nulliparity. Conclusion. Women with unfavourable prepregnant lipid profile had higher risk of having no or only one child. These findings substantiate an association between prepregnant serum lipid levels and number of children. Previously observed associations between low parity and increased cardiovascular mortality may in part be due to pre-existing cardiovascular disease lipid risk factors.publishedVersio

Maternal complications in pregnancy and childbirth for women with epilepsy: time trends in a nationwide cohort

Objective: Obstetric trends show changes in complication rates and maternal characteristics such as caesarean section, induced labour, and maternal age. To what degree such general time trends and changing patterns of antiepileptic drug use influence pregnancies of women with epilepsy (WWE) is unknown. Our aim was to describe changes in maternal characteristics and obstetric complications in WWE over time, and to assess changes in complication risks in WWE relative to women without epilepsy. Methods: This was a nationwide cohort study of all first births in the Medical Birth Registry of Norway, 1999–2016. We estimated maternal characteristics, complication rates, and risks for WWE compared to women without epilepsy. Main maternal outcome measures were hypertensive disorders, bleeding in pregnancy, induction of labour, caesarean section, postpartum hemorrhage, preterm birth, small for gestational age, and epidural analgesia. Time trends were analyzed by logistic regression and comparisons made with interaction analyses. Results: 426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (p<0.005) and use of epidural analgesia (p<0.005), and a reduction in mild preeclampsia (p = 0.006). However, the risk of these outcomes did not change over time. Only the risk of severe preeclampsia increased significantly over time relative to women without epilepsy (p = 0.006). In WWE, folic acid supplementation increased significantly over time (p<0.005), and there was a decrease in smoking during pregnancy (p<0.005), but these changes were less pronounced than for women without epilepsy (p<0.005). Conclusions: During 1999–2016 there were important changes in maternal characteristics and complication rates among WWE. However, outcome risks for WWE relative to women without epilepsy did not change despite changes in antiepileptic drug use patterns. The relative risk of severe preeclampsia increased in women with epilepsy.publishedVersio

Risk of Subsequent Preeclampsia by Maternal Country of Birth: A Norwegian Population-Based Study

In this nationwide population-based study, we investigated the associations of preeclampsia in the first pregnancy with the risk of preeclampsia in the second pregnancy, by maternal country of birth using data from the Medical Birth Registry of Norway and Statistics Norway (1990–2016). The study population included 101,066 immigrant and 544,071 non-immigrant women. Maternal country of birth was categorized according to the seven super-regions of the Global Burden of Disease study (GBD). The associations between preeclampsia in the first pregnancy with preeclampsia in the second pregnancy were estimated using log-binomial regression models, using no preeclampsia in the first pregnancy as the reference. The associations were reported as adjusted risk ratios (RR) with 95% confidence intervals (CI), adjusted for chronic hypertension, year of first childbirth, and maternal age at first birth. Compared to those without preeclampsia in the first pregnancy, women with preeclampsia in the first pregnancy were associated with a considerably increased risk of preeclampsia in the second pregnancy in both immigrant (n = 250; 13.4% vs. 1.0%; adjusted RR 12.9 [95% CI: 11.2, 14.9]) and non-immigrant women (n = 2876; 14.6% vs. 1.5%; adjusted RR 9.5 [95% CI: 9.1, 10.0]). Immigrant women from Latin America and the Caribbean appeared to have the highest adjusted RR, followed by immigrant women from North Africa and the Middle East. A likelihood ratio test showed that the variation in adjusted RR across all immigrant and non-immigrant groups was statistically significant (p = 0.006). Our results suggest that the association between preeclampsia in the first pregnancy and preeclampsia in the second pregnancy might be increased in some groups of immigrant women compared with non-immigrant women in Norway.publishedVersio

Paternal and maternal birthweight and offspring risk of macrosomia at term gestations: A nationwide population study

Background There is a paucity of data on whether parents' macrosomia (birthweight ≥4500 g) status influences the risk of macrosomia in the offspring. The role of maternal overweight in the generational effect of macrosomia is not known. Objective To estimate the risk of macrosomia by parental birthweight at term and evaluate if this risk varied with maternal body mass index (BMI, kg/m2) early in pregnancy. Methods We used data from the Medical Birth Registry of Norway on all singleton term births (37–42 gestational weeks) during 1967–2017. The primary exposure was parental macrosomia, and the outcome was macrosomia in the second generation. The secondary exposure was maternal BMI. We used binomial regression to calculate relative risk (RR) with a 95% confidence interval. We assessed potential unmeasured confounding and selection bias using a probabilistic bias analysis and performed analyses with and without imputation for variables with missing values. Results The data included 647,957 singleton parent-offspring trios born at term. The prevalence of macrosomia was 3.2% (n = 41,396) in the parental generation and 4.0% (n = 25,673) in the offspring generation. Macrosomia in parents was associated with an increased risk of macrosomia in offspring, with the RR for both parents were born macrosomic being 6.53 (95% confidence interval [CI] 5.31, 8.05), only mother macrosomic 3.37 (95% CI 3.17, 3.57) and only father macrosomic RR 2.22 (95% CI 2.12, 2.33). These risks increased by maternal BMI in early pregnancy: if both parents were born macrosomic, 17% of infants were macrosomic among mothers with normal BMI. If both parents were macrosomic and the mothers were obese, 31% of offspring were macrosomic. Macrosomia-related adverse outcomes did not differ with parental macrosomia status. Conclusions Parents' weight at birth and maternal BMI appear to be strongly associated with macrosomia in the offspring delivered at term gestations.publishedVersio

Risk of miscarriage in women with chronic diseases in Norway:A registry linkage study

BACKGROUND: Increased risk of miscarriage has been reported for women with specific chronic health conditions. A broader investigation of chronic diseases and miscarriage risk may uncover patterns across categories of illness. The objective of this study was to study the risk of miscarriage according to various preexisting chronic diseases. METHODS AND FINDINGS: We conducted a registry-based study. Registered pregnancies (n = 593,009) in Norway between 2010 and 2016 were identified through 3 national health registries (birth register, general practitioner data, and patient registries). Six broad categories of illness were identified, comprising 25 chronic diseases defined by diagnostic codes used in general practitioner and patient registries. We required that the diseases were diagnosed before the pregnancy of interest. Miscarriage risk according to underlying chronic diseases was estimated as odds ratios (ORs) using generalized estimating equations adjusting for woman’s age. The mean age of women at the start of pregnancy was 29.7 years (SD 5.6 years). We observed an increased risk of miscarriage among women with cardiometabolic diseases (OR 1.25, 95% CI 1.20 to 1.31; p-value <0.001). Within this category, risks were elevated for all conditions: atherosclerosis (2.22; 1.42 to 3.49; p-value <0.001), hypertensive disorders (1.19; 1.13 to 1.26; p-value <0.001), and type 2 diabetes (1.38; 1.26 to 1.51; p-value <0.001). Among other categories of disease, risks were elevated for hypoparathyroidism (2.58; 1.35 to 4.92; p-value 0.004), Cushing syndrome (1.97; 1.06 to 3.65; p-value 0.03), Crohn’s disease (OR 1.31; 95% CI: 1.18 to 1.45; p-value 0.001), and endometriosis (1.22; 1.15 to 1.29; p-value <0.001). Findings were largely unchanged after mutual adjustment. Limitations of this study include our inability to adjust for measures of socioeconomic position or lifestyle characteristics, in addition to the rareness of some of the conditions providing limited power. CONCLUSIONS: In this registry study, we found that, although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications

Cesarean delivery in Norwegian nulliparous women with singleton cephalic term births, 1967–2020: a population-based study

Background Nulliparous women contribute to increasing cesarean delivery in the Nordic countries and advanced maternal age has been suggested as responsible for rise in cesarean delivery rates in many developed countries. The aim was to describe changes in cesarean delivery rates among nulliparous women with singleton, cephalic, term births by change in sociodemographic factors across 50 years in Norway. Methods We used data from the Medical Birth Registry of Norway and included 1 067 356 women delivering their first, singleton, cephalic, term birth between 1967 and 2020. Cesarean delivery was described by maternal age (5-year groups), onset of labor (spontaneous, induced and pre-labor CD), and time periods: 1967–1982, 1983–1998 and 1999–2020. We combined women’s age, onset of labor and time period into a compound variable, using women of 20–24 years, with spontaneous labor onset during 1967–1982 as reference. Multivariable regression models were used to estimate adjusted relative risk (ARR) of cesarean delivery with 95% confidence interval (CI). Results Overall cesarean delivery increased both in women with and without spontaneous onset of labor, with a slight decline in recent years. The increase was mainly found among women   = 35 years. In women with spontaneous onset of labor, the ARR of CD in women >  = 40 years decreased from 14.2 (95% CI 12.4–16.3) in 1967–82 to 6.7 (95% CI 6.2–7.4) in 1999–2020 and from 7.0 (95% CI 6.4–7.8) to 5.0 (95% CI 4.7–5.2) in women aged 35–39 years, compared to the reference population. Despite the rise in induced onset of labor over time, the ARR of CD declined in induced women >  = 40 years from 17.6 (95% CI 14.4–21.4) to 13.4 (95% CI 12.5–14.3) while it was stable in women 35–39 years. Conclusion Despite growing number of Norwegian women having their first birth at a higher age, the increase in cesarean delivery was found among women < 35 years, while it was stable or decreased in older women. The increase in cesarean delivery cannot be solely explained by the shift to an older population of first-time mothers.publishedVersio

Risk of miscarriage in women with psychiatric disorders

Background Some psychiatric disorders have been associated with increased risk of miscarriage. However, there is a lack of studies considering a broader spectrum of psychiatric disorders to clarify the role of common as opposed to independent mechanisms. Aims To examine the risk of miscarriage among women diagnosed with psychiatric conditions. Method We studied registered pregnancies in Norway between 2010 and 2016 (n = 593 009). The birth registry captures pregnancies ending in gestational week 12 or later, and the patient and general practitioner databases were used to identify miscarriages and induced abortions before 12 gestational weeks. Odds ratios of miscarriage according to 12 psychiatric diagnoses were calculated by logistic regression. Miscarriage risk was increased among women with bipolar disorders (adjusted odds ratio 1.35, 95% CI 1.26–1.44), personality disorders (adjusted odds ratio 1.32, 95% CI 1.12–1.55), attention-deficit hyperactivity disorder (adjusted odds ratio 1.27, 95% CI 1.21–1.33), conduct disorders (1.21, 95% CI 1.01, 1.46), anxiety disorders (adjusted odds ratio 1.25, 95% CI 1.23–1.28), depressive disorders (adjusted odds ratio 1.25, 95% CI 1.23–1.27), somatoform disorders (adjusted odds ratio 1.18, 95% CI 1.07–1.31) and eating disorders (adjusted odds ratio 1.14, 95% CI 1.08–1.22). The miscarriage risk was further increased among women with more than one psychiatric diagnosis. Our findings were robust to adjustment for other psychiatric diagnoses, chronic somatic disorders and substance use disorders. After mutual adjustment for co-occurring psychiatric disorders, we also observed a modest increased risk among women with schizophrenia spectrum disorders (adjusted odds ratio 1.22, 95% CI 1.03–1.44). Conclusions A wide range of psychiatric disorders were associated with increased risk of miscarriage. The heightened risk of miscarriage among women diagnosed with psychiatric disorders highlights the need for awareness and surveillance of this risk group in antenatal care.acceptedVersio