Unveiling sex bias and adverse neonatal outcomes in ultrasound estimation of gestational age: A population-based cohort study.

BACKGROUND: Gestational age estimation by second-trimester ultrasound biometry introduces systematic errors due to sex differences in early foetal growth, consequently increasing the risk of adverse neonatal outcomes. Ultrasound estimation earlier in pregnancy may reduce this bias. OBJECTIVES: To investigate the distribution of sex ratio by gestational age and estimate the risk of adverse outcomes in male foetuses born early-term and female foetuses born post-term by first- and second-trimester ultrasound estimations. METHODS: This population-based study compared two cohorts of births with gestational age based on first- and second-trimester ultrasound in the Medical Birth Registry of Norway between 2016 and 2020. We used a log-binomial regression model to estimate adjusted relative risk (RR) with 95% confidence interval (CI) for Apgar score <7 at 5 min, umbilical artery pH <7.05, neonatal intensive care unit (NICU) admission and respiratory morbidity in relation to foetal sex. RESULTS: The sex ratio at birth in gestational weeks 36-43 showed less male predominance in pregnancies estimated in first compared to second trimester. Any adverse outcome was registered in 627 of 4470 male infants born in gestational weeks 37-38 and 618 of 6406 females born ≥41 weeks. Male infants born in weeks 37-38 had lower risk of NICU admission (RR 0.76, 95% CI 0.58, 0.99), Apgar score <7 at 5 min (RR 0.63, 95% CI 0.28, 1.41) and respiratory morbidity (RR 0.68, 95% CI 0.37, 1.25) in first- compared to second-trimester estimations. Female infants estimated in first trimester born ≥41 weeks had lower risk of umbilical artery pH <7.05, NICU admissions and respiratory morbidity; however, CIs were wide. CONCLUSIONS: Early ultrasound estimation of gestational age may reduce the excess risk of adverse neonatal outcomes and highlight the role of foetal sex and the timing of ultrasound assessment in the clinical evaluation of preterm and post-term pregnancies.

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.

Pregnancy-Associated Maternal Mortality Within One Year After Childbirth: Population-Based Cohort Study.

OBJECTIVE: The objective of this study is to assess associations between pregnancy complications and pregnancy-associated maternal mortality (PAM) within 1 year after childbirth. DESIGN: Population-based cohort study. SETTING: Norway, 1967-2020. POPULATION: 1 237 254 mothers with one or more singleton pregnancies registered in the Medical Birth Registry, 1967-2019 and followed in the Cause of Death Registry to 2020. METHODS: Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for maternal education, age, year of first childbirth and chronic medical conditions. MAIN OUTCOME MEASURES: PAM by lifetime history of pregnancy complications: placental abruption, preeclampsia, preterm birth, perinatal death, small for gestational age (< 2.5 percentile), gestational diabetes and gestational hypertension. RESULTS: Crude OR for PAM was 4.24 (95% CI 3.53-5.10), if complications occurred in the last pregnancy, whereas 2.52 (2.08-3.06) if complications occurred in the first pregnancy, compared to mothers without complications in any pregnancy. Adjusted ORs for PAM when complications occurred in the last pregnancy were, for placental abruption 3.75 (1.20-11.72), preeclampsia: 4.42 (3.17-6.15), preterm birth: 4.32 (3.25-5.75), perinatal death: 24.18 (16.66-35.08), small for gestational age: 2.90 (1.85-4.54), gestational diabetes: 1.43 (0.63-3.25) and pregnancy hypertension: 2.05 (1.12-3.74) compared to mothers without complications. The OR for PAM increased slightly by increasing the number of complicated pregnancies but the trend was stronger for increasing number of complications in the last pregnancy (e.g., during 1999-2019: one complication; 4.14 [2.79-6.13], two complications; 11.50 [6.81-19.43]). CONCLUSION: Complications in the last pregnancy were more strongly associated with PAM than those in the first pregnancy.

Risk of adverse pregnancy outcomes in twin- and singleton-born women: An inter-generational cohort study.

OBJECTIVE: To compare the risk of adverse pregnancy outcomes between twin-born and singleton-born women. We also evaluated whether in utero exposure to pre-eclampsia or preterm delivery affected adverse pregnancy outcomes in women's own pregnancies. DESIGN: Population-based cohort study. SETTING: Medical Birth Registry of Norway 1967-2020. POPULATION: 9184 twin-born and 492 894 singleton-born women during 1967-2005, with their later pregnancies registered during 1981-2020. METHODS: Data from an individual's birth were linked to their later pregnancies. We used generalised linear models with log link binomial distribution to obtain exponentiated regression coefficients that estimated relative risks (RRs) with 95% confidence intervals (CIs) for associations between twin- or singleton-born women and later adverse pregnancy outcomes. MAIN OUTCOME MEASURES: Pre-eclampsia, preterm delivery or perinatal loss in twin-born compared with singleton-born women. RESULTS: There was no increased risk for adverse outcomes in twin-born compared with singleton-born women: adjusted RRs for pre-eclampsia were 1.00 (95% CI 0.93-1.09), for preterm delivery 0.96 (95% CI 0.90-1.02) and for perinatal loss 1.00 (95% CI 0.84-1.18). Compared with singleton-born women exposed to pre-eclampsia in utero, twin-born women exposed to pre-eclampsia had lower risk of adverse outcomes in their own pregnancies; the aRR for pre-eclampsia was 0.73 (95% CI 0.58-0.91) and for preterm delivery was 0.71 (95% CI 0.56-0.90). Compared with preterm singleton-born women, preterm twin-born women did not differ in terms of risk of pre-eclampsia (aRR 1.05, 95% CI 0.92-1.21) or perinatal loss (aRR 0.99, 95% CI 0.71-1.37) and had reduced risk of preterm delivery (RR 0.83, 95% CI 0.74-0.94). CONCLUSIONS: Twin-born women did not differ from singleton-born women in terms of risk of adverse pregnancy outcomes. Twin-born women exposed to pre-eclampsia in utero, had a lower risk of pre-eclampsia and preterm delivery compared with singleton-born women exposed to pre-eclampsia.

Associations between term cesarean delivery in the first pregnancy and second-pregnancy preterm delivery.

INTRODUCTION: Cesarean delivery has been shown to increase the risk of preterm delivery in future pregnancies. The association could be a direct result of the procedure, or because the indications that led to the cesarean delivery also increase the risk of preterm delivery in later pregnancies. MATERIAL AND METHODS: 298 901 mothers with first and second singleton deliveries from 1999 to 2020 were investigated using data from the Medical Birth Registry of Norway linked with Statistics Norway. The mothers were categorized by mode of cesarean delivery (total, emergency and planned) and vaginal delivery at term in the first pregnancy. We used log-binomial regression models to estimate relative risks with 95% confidence intervals (CI) of iatrogenic and spontaneous preterm delivery <37 gestational weeks in the second pregnancy. Second, we explored the role of recurrent placental disease in preterm delivery by comparing estimates in mothers with placental disease in neither or both pregnancies. RESULTS: 8243 mothers (2.8%) had a preterm delivery in the second pregnancy. The adjusted relative risk (aRR) of preterm delivery was 1.24 (95% CI 1.17-1.32) after cesarean compared with vaginal delivery in the first pregnancy. The association was stronger in previous planned compared with emergency cesarean delivery (aRR 1.52, 95% CI 1.30-1.77 and aRR 1.21, 95% CI 1.14-1.29, respectively). Spontaneous preterm delivery was not associated with the previous mode of delivery; the risk was confined to iatrogenic preterm delivery after both emergency and planned cesarean delivery (aRR 1.69, 95% CI 1.52-1.87 and aRR 2.65, 95% CI 2.12-3.30, respectively). Mothers with placental disease in both pregnancies had a sixfold increased risk of preterm delivery in the second pregnancy compared with mothers with no placental disease, however, the association between mode of delivery and subsequent preterm delivery was similar in mothers with and without placental disease in the pregnancies. CONCLUSIONS: Compared with vaginal term delivery in the first pregnancy, cesarean delivery increases the risk of iatrogenic, but not spontaneous preterm delivery in the next pregnancy. Although strongly associated with preterm delivery, placental disease had limited influence on the estimates.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

INTRODUCTION: The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. MATERIAL AND METHODS: Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. RESULTS: A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). CONCLUSIONS: The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

Pre-pregnancy obesity among immigrant and non-immigrant women in Norway: Prevalence, trends, and subgroup variations.

INTRODUCTION: This study assessed prevalence and time trends of pre-pregnancy obesity in immigrant and non-immigrant women in Norway and explored the impact of immigrants' length of residence on pre-pregnancy obesity prevalence. MATERIAL AND METHODS: Observational data from the Medical Birth Registry of Norway and Statistics Norway for the years 2016-2021 were analyzed. Immigrants were categorized by their country of birth and further grouped into seven super regions defined by the Global Burden of Disease study. Pre-pregnancy obesity was defined as a body mass index ≥30.0 kg/m2, with exceptions for certain Asian subgroups (≥27.5 kg/m2). Statistical analysis involved linear regressions for trend analyses and log-binomial regressions for prevalence ratios (PRs). RESULTS: Among 275 609 pregnancies, 29.6% (N = 81 715) were to immigrant women. Overall, 13.6% were classified with pre-pregnancy obesity: 11.7% among immigrants and 14.4% among non-immigrants. Obesity prevalence increased in both immigrants and non-immigrants during the study period, with an average yearly increase of 0.62% (95% confidence interval [CI]: 0.55, 0.70). Obesity prevalence was especially high in women from Pakistan, Chile, Somalia, Congo, Nigeria, Ghana, Sri Lanka, and India (20.3%-26.9%). Immigrant women from "Sub-Saharan Africa" showed a strong association between longer residence length and higher obesity prevalence (≥11 years (23.1%) vs. <1 year (7.2%); adjusted PR = 2.40; 95% CI: 1.65-3.48), particularly in women from Kenya, Eritrea, and Congo. CONCLUSIONS: Prevalence of maternal pre-pregnancy obesity increased in both immigrant and non-immigrant women from 2016 to 2021. Several immigrant subgroups displayed a considerably elevated obesity prevalence, placing them at high risk for adverse obesity-related pregnancy outcomes. Particular attention should be directed towards women from "Sub-Saharan Africa", as their obesity prevalence more than doubled with longer residence.

Associations between non-registered ultrasound examination in pregnancy and adverse perinatal outcomes in immigrant and non-immigrant women: a Norwegian population-based study 1999-2016.

BACKGROUND: Prenatal ultrasound examinations are important to detect placental dysfunction. Several ultrasound-detected abnormalities can be managed during pregnancy or childbirth, thus improve health outcomes. Maternal birth country is known to influence the risk of placental dysfunction, but little is known about the possible mechanisms of this relation. AIMS: (a) To estimate the proportion of non-registered prenatal ultrasound examinations; (b) to examine associations between non-registered ultrasound examinations and adverse perinatal outcomes, by migrant-related factors, in women giving birth in Norway. METHODS: Individually linked data from the Medical Birth Registry of Norway and Statistics Norway, 1999-2016, comprising 999,760 singleton pregnancies to immigrants (n=196,220) and non-immigrants (n=803,540). Crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated using logistic regression with robust standard error estimations, adjusted for year of childbirth, maternal age, parity, maternal smoking, educational level and Norwegian health region at birth. RESULTS: Compared with non-immigrants, immigrant women had a higher proportion of non-registered ultrasound examinations (2.3% vs. 4.3%; aOR 2.0 (95% CI 1.9, 2.0)). Compared with women with ultrasound examination, the aOR for perinatal mortality for women with non-registered ultrasound was 2.27 (95% CI 1.85, 2.79) for immigrants and 3.61 (3.21, 4.07) for non-immigrants. Non-registered ultrasound examination was also associated with placental abruption (aOR 1.32 (1.08, 1.63)) for non-immigrant women, but it was not associated with preeclampsia. Compared with non-immigrants, immigrant women have a higher proportion of non-registered data on prenatal ultrasound examinations. Both immigrants and non-immigrants with non-registered ultrasound examinations have an increased aOR of perinatal mortality. Non-immigrant women also had an increased aOR for placental abruption.

Birth Weight in Consecutive Pregnancies and Maternal Cardiovascular Disease Mortality Among Spontaneous and Iatrogenic Term Births: A Population-Based Cohort Study.

Knowledge on the association between offspring birth weight and long-term risk of maternal cardiovascular disease (CVD) mortality is often based on firstborn infants without consideration of women's consecutive births. We studied long-term CVD mortality according to offspring birth weight patterns among women with spontaneous and iatrogenic term deliveries in Norway (1967-2020). We constructed birth weight quartiles (Qs) by combining standardized birth weight with gestational age in quartiles (Q1, Q2/Q3, and Q4) for the women's first 2 births. Mortality was estimated using Cox regression and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Changes in offspring birth weight quartiles were associated with long-term maternal CVD mortality. Compared with women who had 2 term infants in Q2/Q3, women with a first offspring in Q2/Q3 and a second in Q1 had higher mortality risk (HR = 1.33, 95% CI: 1.18, 1.50), while risk was lower if the second offspring was in Q4 (HR = 0.78, 95% CI: 0.67, 0.91). The risk increase associated with having a first infant in Q1 was eliminated if the second offspring was in Q4 (HR = 0.99, 95% CI: 0.75, 1.31). These patterns were similar for women with iatrogenic and spontaneous deliveries. Inclusion of information from subsequent births revealed heterogeneity in maternal CVD mortality which was not captured when using only information based on the first offspring.

The relationship between cesarean delivery and fecundability: a population-based cohort study.

BACKGROUND: Previous studies have found that women who undergo cesarean delivery have fewer pregnancies. Cesarean delivery is also more common among women with lower fecundability. The potential role of cesarean delivery in reduced fecundability is not known. OBJECTIVE: This study aimed to assess the bidirectional relationship between cesarean delivery and fecundability. STUDY DESIGN: This was a prospective cohort study based on data from the Norwegian Mother, Father, and Child Cohort study linked with the Medical Birth Registry of Norway. We estimated the fecundability ratio (per cycle probability of pregnancy) and relative risk of infertility (time to pregnancy ≥12 months) by mode of delivery in the previous delivery among 42,379 women. For the reverse association, we estimated the relative risk of having a cesarean delivery by fecundability (the number of cycles women needed to conceive) among 74,024 women. RESULTS: The proportion of women with infertility was 7.3% (2707/37,226) among women with a previous vaginal delivery and 9.9% (508/5153) among women with a previous cesarean delivery, yielding an adjusted relative risk of 1.21 (95% confidence interval, 1.10-1.33). Women with a previous cesarean delivery also had a lower fecundability ratio (0.90; 95% confidence interval, 0.88-0.93) than women with a previous vaginal delivery. When assessing the reverse association between fecundability and cesarean delivery, we found that women who did not conceive within 12 or more cycles had a higher risk for cesarean delivery (adjusted relative risk, 1.57; 95% confidence interval, 1.48-1.66) than women who conceived within the first 2 cycles. The associations remained after controlling for sociodemographic and clinical risk factors and were observed across parity groups. CONCLUSION: Among women with more than 1 child, those who had a previous cesarean delivery subsequently had a lower fecundability ratio and an increased infertility risk than those who had a vaginal delivery. However, women who needed a longer time to conceive were also more prone to be delivered by cesarean delivery, indicating a bidirectional relationship between cesarean delivery and fecundability. This could suggest a common underlying explanatory mechanism and that the surgical procedure itself may not or only partly directly influence fecundability.

Long-term cardiovascular mortality in women with twin pregnancies by lifetime reproductive history.

BACKGROUND: Women with one lifetime singleton pregnancy have increased risk of cardiovascular disease (CVD) mortality compared with women who continue reproduction particularly if the pregnancy had complications. Women with twins have higher risk of pregnancy complications, but CVD mortality risk in women with twin pregnancies has not been fully described. OBJECTIVES: We estimated risk of long-term CVD mortality in women with naturally conceived twins compared to women with singleton pregnancies, accounting for lifetime number of pregnancies and pregnancy complications. METHODS: Using linked data from the Medical Birth Registry of Norway and the Norwegian Cause of Death Registry, we identified 974,892 women with first pregnancy registered between 1967 and 2013, followed to 2020. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for maternal CVD mortality were estimated by Cox regression for various reproductive history (exposure categories): (1) Only one twin pregnancy, (2) Only one singleton pregnancy, (3) Only two singleton pregnancies, (4) A first twin pregnancy and continued reproduction, (5) A first singleton pregnancy and twins in later reproduction and (6) Three singleton pregnancies (the referent group). Exposure categories were also stratified by pregnancy complications (pre-eclampsia, preterm delivery or perinatal loss). RESULTS: Women with one lifetime pregnancy, twin or singleton, had increased risk of CVD mortality (adjusted hazard [HR] 1.72, 95% confidence interval [CI] 1.21, 2.43 and aHR 1.92, 95% CI 1.78, 2.07, respectively), compared with the referent of three singleton pregnancies. The hazard ratios for CVD mortality among women with one lifetime pregnancy with any complication were 2.36 (95% CI 1.49, 3.71) and 3.56 (95% CI 3.12, 4.06) for twins and singletons, respectively. CONCLUSIONS: Women with only one pregnancy, twin or singleton, had increased long-term CVD mortality, however highest in women with singletons. In addition, twin mothers who continued reproduction had similar CVD mortality compared to women with three singleton pregnancies.

Is the increasing prevalence of labor induction accompanied by changes in pregnancy outcomes? An observational study of all singleton births at gestational weeks 37-42 in Norway during 1999-2019.

INTRODUCTION: Induction of labor is often performed to prevent adverse perinatal and maternal outcomes, and has become increasingly common. We studied whether changes in prevalence of labor induction in gestational weeks 37-42 weeks were accompanied by changes in adverse pregnancy outcomes or mode of delivery. MATERIAL AND METHODS: We used data from the Medical Birth Registry of Norway, and included all singleton births in gestational weeks 37-42 in Norway, 1999-2019 (n = 1 127 945). We calculated the prevalence of labor induction and outcome measures according to year of birth. We repeated these calculations for each gestational week at birth. RESULTS: The prevalence of labor induction increased from 9.7% to 25.9%, and the increase was particularly high in gestational week 41. A modest decline in fetal deaths was observed in all gestational weeks, except gestational week 41. The overall decline was from 0.18% in 1999-2004 to 0.13% during 2015-2019. There were no overall changes in other perinatal outcomes. The prevalence of postpartum hemorrhage ≥500 ml increased from 11.4% in 1999 to 30.1% in 2019, and operative deliveries increased slightly. The prevalence of acute cesarean section increased from 6.5% to 9.3%, whereas vacuum and/or forceps assisted deliveries increased from 7.8% to 10.4%. CONCLUSIONS: A high increase in labor inductions was accompanied by a modest decline in fetal deaths, but no decline in other adverse perinatal outcomes. In settings where the prevalence of adverse perinatal outcomes is low, the beneficial effect of increased use of labor induction may not outweigh the side effects or the costs.

Pregestational maternal risk factors for preterm and term preeclampsia: A population-based cohort study.

INTRODUCTION: Most studies on factors affecting the risk of preeclampsia have not separated preterm from term preeclampsia, and we still know little about whether the predisposing conditions have a differentiated effect on the risk of preterm and term preeclampsia. Our aim was to assess whether diabetes type 1 and 2, chronic kidney disease, asthma, epilepsy, rheumatoid arthritis and chronic hypertension were differentially associated with preterm and term preeclampsia. MATERIAL AND METHODS: This is a nationwide, population-based cohort study containing all births registered in the Medical Birth Registry of Norway from 1999 to 2016. Multinomial logistic regression analysis was used to estimate relative risk ratios (RRRs) with 95% confidence intervals (95% CIs), adjusting for maternal age, parity, multiple gestation and all other studied maternal risk factors. RESULTS: We registered 1 044 860 deliveries, of which 9533 (0.9%) women had preterm preeclampsia (<37 weeks) and 26 504 (2.5%) women had term preeclampsia (>37 weeks). Most of the assessed maternal risk factors were associated with increased risk for both preterm and term preeclampsia, with adjusted RRRs ranging from 1.2 to 10.5 (preterm vs no preeclampsia) and 0.9-5.7 (term vs no preeclampsia). Diabetes type 1 and 2 (RRR preterm vs term preeclampsia 2.89, 95% CI 2.46-3.39 and RRR 1.68, 95% CI 1.25-2.25, respectively), chronic kidney disease (RRR 1.55, 95% CI 1.11-2.17) and chronic hypertension (RRR 1.85, 95% CI 1.63-2.10) were more strongly associated with preterm than term preeclampsia in adjusted analyses. For asthma, epilepsy and rheumatoid arthritis, RRRs were closer to one and not significant when comparing risk of preterm and term preeclampsia. Main results were similar when using a diagnosis at <34 weeks to define preterm preeclampsia. CONCLUSIONS: Diabetes type 1 and 2, chronic kidney disease and chronic hypertension were more strongly associated with preterm than term preeclampsia.

Birthweight of the subsequent singleton pregnancy following a first twin or singleton pregnancy.

INTRODUCTION: Birthweight is an important pregnancy indicator strongly associated with infant, child, and later adult life health. Previous studies have found that second-born babies are, on average, heavier than first-born babies, indicating an independent effect of parity on birthweight. Existing data are mostly based on singleton pregnancies and do not consider higher order pregnancies. We aimed to compare birthweight in singleton pregnancies following a first twin pregnancy relative to a first singleton pregnancy. MATERIAL AND METHODS: This was a prospective registry-based cohort study using maternally linked offspring with first and subsequent pregnancies registered in the Medical Birth Registry of Norway between 1967 and 2020. We studied offspring birthweights of 778 975 women, of which 4849 had twins and 774 126 had singletons in their first pregnancy. Associations between twin or singleton status of the first pregnancy and birthweight (grams) in subsequent singleton pregnancies were evaluated by linear regression adjusted for maternal age at first delivery, year of first pregnancy, maternal education, and country of birth. We used plots to visualize the distribution of birthweight in the first and subsequent pregnancies. RESULTS: Mean combined birthweight of first-born twins was more than 1000 g larger than mean birthweight of first-born singletons. When comparing mean birthweight of a subsequent singleton baby following first-born twins with those following first-born singletons, the adjusted difference was just 21 g (95% confidence interval 5-37 g). CONCLUSIONS: Birthweights of the subsequent singleton baby were similar for women with a first twin or a first singleton pregnancy. Although first twin pregnancies contribute a greater combined total offspring birthweight including more extensive uterine expansion, this does not explain the general parity effect seen in birthweight. The physiological reasons for increased birthweight with parity remain to be established.

Pregnancy complications in last pregnancy and mothers' long-term cardiovascular mortality: does the relation differ from that of complications in first pregnancy? A population-based study.

BACKGROUND: Women who experience complications in first pregnancy are at increased risk of cardiovascular disease (CVD) later in life. Little corresponding knowledge is available for complications in later pregnancies. Therefore, we assessed complications (preeclampsia, preterm birth, and offspring small for gestational age) in first and last pregnancies and the risk of long-term maternal CVD death, taking women´s complete reproduction into account. DATA AND METHODS: We linked data from the Medical Birth Registry of Norway to the national Cause of Death Registry. We followed women whose first birth took place during 1967-2013, from the date of their last birth until death, or December 31st 2020, whichever occurred first. We analysed risk of CVD death until 69 years of age according to any complications in last pregnancy. Using Cox regression analysis, we adjusted for maternal age at first birth and level of education. RESULTS: Women with any complications in their last or first pregnancy were at higher risk of CVD death than mothers with two-lifetime births and no pregnancy complications (reference). For example, the adjusted hazard ratio (aHR) for women with four births and any complications only in the last pregnancy was 2.85 (95% CI, 1.93-4.20). If a complication occurred in the first pregnancy only, the aHR was 1.74 (1.24-2.45). Corresponding hazard ratios for women with two births were 1.82 (CI, 1.59-2.08) and 1.41 (1.26-1.58), respectively. CONCLUSIONS: The risk for CVD death was higher among mothers with complications only in their last pregnancy compared to women with no complications, and also higher compared to mothers with a complication only in their first pregnancy.

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 while it was stable or decreased in 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.

Preconception leisure-time physical activity and family history of stroke and myocardial infarction associate with preterm delivery: findings from a Norwegian cohort.

BACKGROUND: Preterm birth poses short and long-term health consequences for mothers and offspring including cardiovascular disease sequelae. However, studies evaluating preexisting family history of cardiovascular disease and risk factors, such as physical activity, as they relate prospectively to risk of delivering preterm are lacking. OBJECTIVES: To evaluate whether preconception past-year weekly leisure-time physical activity or a family history of stroke or of myocardical infarction prior to age 60 years in first degree relatives associated, prospectively, with preterm delivery. DESIGN: Cohort study. Baseline data from Cohort Norway (1994-2003) health surveys were linked to the Medical Birth Registry of Norway for identification of all subsequent births (1994-2012). Logistic regression models provided odds ratios (OR) and 95% confidence intervals (CI) for preterm delivery (< 37 weeks gestation); multinomial logistic regression provided OR for early preterm (< 34 weeks) and late preterm (34 through to end of 36 weeks gestation) relative to term deliveries. RESULTS: Mean (SD) length of time from baseline health survey participation to delivery was 5.6 (3.5) years. A family history of stroke associated with a 62% greater risk for late preterm deliveries (OR 1.62; CI 1.07-2.47), while a family history of myocardial infarction associated with a 66% greater risk of early preterm deliveries (OR 1.66; CI 1.11-2.49). Sensitivity analyses, removing pregnancies complicated by hypertensive disorders of pregnancy, diabetes mellitus, and stillbirth deliveries, gave similar results. Preconception vigorous physical activity of three or more hours relative to less than 1 h per week associated with increased risk of early preterm delivery (OR 1.52; 95% CI 1.01-2.30), but not late or total preterm deliveries. Light physical activity of three or more hours per week relative to less activity prior to pregnancy was not associated with early, late, or total preterm deliveries. CONCLUSIONS: Results suggest that family history of cardiovascular disease may help identify women at risk for preterm delivery. Further, research is needed regarding preconception and very early pregnancy vigorous physical activity and associated risks.

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.

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. 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.

Placental abruption in immigrant women in Norway: A population-based study.

INTRODUCTION: Placental abruption is a serious complication in pregnancy. Its incidence varies across countries, but the information of how placental abruption varies in immigrant populations is limited. The aims of this study were to estimate the incidence of placental abruption in immigrant women compared with non-immigrants by maternal country and region of birth, reason for immigration, and length of residence. MATERIAL AND METHODS: We conducted a nationwide population-based study using data from the Medical Birth Registry of Norway and Statistics Norway (1990-2016). The study sample included 1 558 174 pregnancies, in which immigrant women accounted for 245 887 pregnancies and 1 312 287 pregnancies were to non-immigrants. Crude and adjusted odds ratios with 95% CI for placental abruption in immigrant women compared with non-immigrants were estimated by logistic regression with robust standard error estimations (accounting for within-mother clustering). Adjustment variables included year of birth, maternal age, parity, multiple pregnancies, chronic hypertension, and level of education. RESULTS: The incidence of placental abruption decreased during the study period for both immigrants (from 0.68% to 0.44%) and non-immigrants (from 0.80% to 0.34%). Immigrant women from sub-Saharan Africa had an adjusted odds ratio of 1.35 (95% CI 1.15-1.58) compared with non-immigrants for placental abruption, whereas immigrant women from Ethiopia had an adjusted odds ratio of 2.39 (95% CI 1.67-3.41). We found a small variation in placental abruption incidence by other countries or regions of birth, length of residence, and reason for immigration. CONCLUSIONS: Immigrant women from sub-Saharan Africa, especially Ethiopia, have increased odds for placental abruption when giving birth in Norway. Reason for immigration and length of residence had little impact on the incidence of placental abruption.