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Objectives (i) Estimate the proportion of non-registered prenatal ultrasound examinations; (ii) Examine associations between non-registered ultrasound examinations and adverse perinatal outcomes, by migrant-related factors, in women giving birth in Norway. Design A national population-based study. Setting and sample 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). Methods Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated using logistic regression with robust standard error estimations, adjusted for year of childbirth, maternal age, parity, maternal smoking during pregnancy, educational level, and Norwegian health region at birth. Main outcome measures Prenatal ultrasound examinations; perinatal mortality; placental abruption; preeclampsia. Results Compared to non-immigrants, immigrant women had a higher proportion of non-registered ultrasound examinations (2.3% vs. 4.3% respectively). Compared to 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 not for immigrant women. Non-registered ultrasound examination was not associated with preeclampsia in either immigrant or non-immigrant women. Conclusion Compared to 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, but no association was found for preeclampsia. Non-immigrant women had an increased aOR for placental abruption.

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. publishedVersion

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. publishedVersion

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. publishedVersion

ObjectiveWe have previously found that allergy is a risk factor for early-onset pre-eclampsia. The aim of this study was to assess the association between pregestational maternal use of antihistamines and early-onset pre-eclampsia.DesignA population-based cohort study.Setting and participantsAll women giving birth in Norway 2004–2016, including 692 487 pregnancies. Data from the Medical Birth Registry of Norway were linked with data from the Norwegian Prescription Database. Prescriptions of antihistamines were divided into three groups: before pregnancy (InterventionsUse of antihistamines in relation to pregnancy in allergic women.Main outcome measuresDevelopment of early-onset pre-eclampsia.Results2997 (0.43%) and 5769 (0.83%) women had pre-eclampsia ConclusionsAntihistamine use before or during placentation was associated with reduced risk of developing early-onset pre-eclampsia in allergic women compared with women using antihistamines after placentation.

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, In this registry data study, Maria Magnus and colleagues study associations between miscarriage risk and chronic conditions., Author summary Why was this study done? Scattered findings indicate that women with different chronic disease have an increased risk of miscarriage. To our knowledge, none of the existing studies have evaluated a broader range of chronic diseases to further evaluate the role of common as opposed to independent biological mechanisms. What did the researchers do and find? With linked data from Norwegian national registries (including 593,009 pregnancies), we examined the risk of miscarriage according to 25 different chronic diseases diagnosed prior to pregnancy. Although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. Other conditions associated with risk of miscarriage included hypoparathyroidism, Cushing syndrome, Crohn’s disease, and endometriosis. What do these findings mean? This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications. Further investigation is necessary to better understand the underlying mechanisms resulting in an increased risk of miscarriage across a range of chronic diseases.

Introduction With increasing cesarean section rates, adverse pregnancy outcomes such as preterm delivery and small-for-gestational-age continue to be public health challenges. Besides having high co-occurrence and interrelation, it is suggested that these outcomes, along with preeclampsia, are associated with reduced subsequent fertility. On the other hand, the loss of a child during the perinatal period is associated with increased reproduction. Failure to consider this factor when estimating the effects of pregnancy outcomes on future reproduction may lead to erroneous conclusions. However, few studies have explored to what degree a perinatal loss contributes to having a next pregnancy in various adverse pregnancy outcomes. Material and methods This was a population-based study of mothers giving birth to their first singleton infant (≥22 gestational weeks) during 1967-2007 who were followed for the occurrence of a second birth in the Medical Birth Registry of Norway until 2014. Relative risks with 95% confidence intervals for having one lifetime pregnancy by preterm delivery, small-for-gestational-age, preeclampsia and cesarean section were obtained by generalized linear models for the binary family and adjusted for maternal age at first birth, education and year of first childbirth. Main outcome measure was having one lifetime pregnancy. Results Nearly 900 000 women gave birth to their first singleton infant in 1967-2007, of which 16% had only one lifetime pregnancy. These women were older at first delivery, had less education and there was a higher proportion of unmarried women than women with two or more births. In women with pregnancy complications where the infant survived the perinatal period, there were the following relative risks for one lifetime pregnancy: increased preterm delivery: 1.21 (1.19-1.22)], small-for-gestational-age: 1.13 (1.12-1.15), preeclampsia: 1.09 (1.07-1.11), cesarean section: 1.24 (1.23-1.25). The risk was significantly reduced if the child was lost (preterm delivery: 0.63 [0.59-0.68], small-for-gestational-age: 0.57 [0.51-0.63], preeclampsia: 0.69 [0.59-0.80], cesarean section: 0.67 [0.56-0.79]), compared with women with no perinatal loss and no adverse outcome. Conclusions The associations between adverse outcomes of pregnancy and the risk of having one lifetime pregnancy were strongly modified by child survival in the perinatal period.

BACKGROUND The rising prevalence of gestational diabetes mellitus (GDM) calls for the use of innovative methods to inform and empower these pregnant women. An information chatbot, Dina, was developed for women with GDM and is Norway’s first health chatbot, integrated into the national digital health platform. OBJECTIVE The aim of this study is to investigate what kind of information users seek in a health chatbot providing support on GDM. Furthermore, we sought to explore when and how the chatbot is used by time of day and the number of questions in each dialogue and to categorize the questions the chatbot was unable to answer (fallback). The overall goal is to explore quantitative user data in the chatbot’s log, thereby contributing to further development of the chatbot. METHODS An observational study was designed. We used quantitative anonymous data (dialogues) from the chatbot’s log and platform during an 8-week period in 2018 and a 12-week period in 2019 and 2020. Dialogues between the user and the chatbot were the unit of analysis. Questions from the users were categorized by theme. The time of day the dialogue occurred and the number of questions in each dialogue were registered, and questions resulting in a fallback message were identified. Results are presented using descriptive statistics. RESULTS We identified 610 dialogues with a total of 2838 questions during the 20 weeks of data collection. Questions regarding blood glucose, GDM, diet, and physical activity represented 58.81% (1669/2838) of all questions. In total, 58.0% (354/610) of dialogues occurred during daytime (8 AM to 3:59 PM), Monday through Friday. Most dialogues were short, containing 1-3 questions (340/610, 55.7%), and there was a decrease in dialogues containing 4-6 questions in the second period (P=.013). The chatbot was able to answer 88.51% (2512/2838) of all posed questions. The mean number of dialogues per week was 36 in the first period and 26.83 in the second period. CONCLUSIONS Frequently asked questions seem to mirror the cornerstones of GDM treatment and may indicate that the chatbot is used to quickly access information already provided for them by the health care service but providing a low-threshold way to access that information. Our results underline the need to actively promote and integrate the chatbot into antenatal care as well as the importance of continuous content improvement in order to provide relevant information.

BackgroundSome 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.AimsTo examine the risk of miscarriage among women diagnosed with psychiatric conditions.MethodWe 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).ConclusionsA 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.

Objective 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. Design Nationwide population-based study. Setting Data from the Medical Birth Registry of Norway and Statistics Norway (1990-2016). Sample 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. Methods Crude and adjusted odds ratios with 95% confidence intervals (CI) for placental abruption in immigrant women compared to 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. Main outcome measures Placental abruption 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 the sub-Saharan African region had an adjusted odds ratio of 1.35 (95% CI: 1.15-1.58) compared to 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. Conclusion 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.

Objective: To estimate recurrence risk of gestational diabetes mellitus (GDM) by interpregnancy weight change. Design: Population-based cohort study. Setting and population: Data from the Swedish (1992–2010) and the Norwegian (2006–2014) Medical Birth Registries on 2763 women with GDM in first pregnancy, registered with their first two singleton births and available information on height and weight. Methods: Interpregnancy weight change (BMI in second pregnancy minus BMI in first pregnancy) was categorised in six groups by BMI units. Relative risks (RRs) of GDM recurrence were obtained by general linear models for the binary family and adjusted for confounders. Analyses were stratified by BMI in first pregnancy (2 units (RR 0.72, 95% CI 0.59–0.89) and increased if BMI increased by ≥4 units (RR 1.26, 95% CI 1.05–1.51) compared wth women with stable BMI (−1 to 1 units). In normal weight women (BMI

This is the pre-peer reviewed version of the following article: Mæland, K. S., Morken, N. H., Schytt, E., Aasheim, V., & Nilsen, R. M. (2021). Placental abruption in immigrant women in Norway: A population‐based study. Acta Obstetricia et Gynecologica Scandinavica., which has been published in final form at https://doi.org/10.1111/aogs.14067. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Introduction Placental abruption is a serious complication in pregnancy. While its incidence varies across countries, the information of how abruption varies in immigrant populations is limited. The aims of this study were to estimate the incidence of placental abruption in immigrant women compared to 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% confidence intervals (CI) for placental abruption in immigrant women compared to 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 the sub‐Saharan African region had an adjusted odds ratio of 1.35 (95% CI: 1.15‐1.58) compared to 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.

Objective To examine the association between availability of obstetric institutions and risk of eclampsia, HELLP-syndrome, or delivery before 35 gestational weeks in preeclamptic pregnancies. Study design National population-based retrospective cohort study of deliveries in Norway, 1999–2009 (n = 636738) using data from The Medical Birth Registry of Norway and Statistics Norway. Main exposures were institution availability, measured by travel time to the nearest obstetric institution, and place of delivery. We computed relative risks (RR) with 95% confidence intervals (CI) using travel time ≤1 h as reference. We stratified analyses by parity and preeclampsia, and adjusted for socio-demographic and medical risk factors. Successive deliveries were linked using the national identification number. Results We identified 1387 eclampsia/HELLP cases (0.2%) and 3004 (0.5%) deliveries before 35 weeks in preeclamptic pregnancies. Nulliparous women living >1 h from any obstetric institution had 50% increased risk of eclampsia/HELLP (0.50 versus 0.35%, adjusted RR 1.5; 95 %CI 1.1–1.9). Parous women living >1 h from emergency institutions had a doubled risk of eclampsia (0.6‰ versus 0.3‰, adjusted RR 2.0; 1.2–3.3). Women without preeclampsia in the present pregnancy or history of preeclampsia constituted all eclampsia/HELLP cases in midwife-led institutions, 39–50% of cases in emergency institutions, and 78% of cases (135/173) in subsequent deliveries. Women with risk factors delivered in the emergency institutions, indicating well-implemented selective referral. Conclusion The study shows the importance of available obstetric institutions. Policymakers and clinicians should consider the distribution of potential benefits and burdens when planning and evaluating the obstetric health service structure.

Introduction Some studies have suggested that women may avoid further pregnancies after experiencing a pregnancy affected by a hypertensive disorder. Large population-based studies are needed to better understand the outcomes of later pregnancies among women who have a history of hypertensive disorders of pregnancy. The aims of the study were to assess outcomes of the second pregnancy and second delivery rate among women experiencing Hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome in their first pregnancy. Material and methods This population-based registry study included all women with a first delivery registered in the Medical Birth Registry of Norway from 1999 to 2014 (n = 418 897). Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for adverse outcomes of the second delivery and the probability of no second delivery among women with HELLP syndrome in first pregnancy compared with women without HELLP syndrome. We also compared outcomes in the first and second pregnancies among women with HELLP syndrome in first. Results HELLP syndrome occurred in 0.24% of first pregnancies (n = 1006). Among women with HELLP syndrome in their first pregnancy, adverse outcomes were substantially less frequent in the second pregnancy: preterm deliveries declined from 56.0% to 14.2%, and small for gestational age from 6.6% to 2.8%. More than 75% had no hypertensive disorder in their second pregnancy. Still, compared with women without a history of HELLP syndrome, ORs for adverse outcomes in second pregnancies were increased: preterm birth (OR 3.7, 95% CI 2.8-4.8), small for gestational age (OR 2.7, 95% CI 1.6-4.8), perinatal death (OR 3.1, 95% CI 1.4-7.0), placental abruption (OR 4.2, 95% CI 1.8-9.4) and hypertensive complication (OR 8.3, 95% CI 6.7-10.3). HELLP syndrome did not influence the probability of a second delivery. Conclusions Among women with HELLP syndrome in their first pregnancy, the occurrence of adverse pregnancy outcomes was substantially reduced in the second pregnancy. However, compared with unaffected women, they were still at greater risk of pregnancy complications.

ObjectiveObstetric 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.MethodsThis 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.Results426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (pConclusionsDuring 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.

Objectives Childbearing at extremely advanced maternal age is a globally increasing trend, but only a few studies have described the outcomes of these pregnancies. The aim of this study was to describe the occurrence of childbearing at age 50 and up in the Nordic countries, as well as to examine the frequency of adverse obstetric and neonatal outcomes. Study design A descriptive population-based study was designed. Data from 1991 to 2013 were collected from the Medical Birth Registries in Denmark, Finland, Norway and Sweden. We investigated the occurrence of antepartum, delivery and neonatal outcomes. Results A total of 170 deliveries, in 141 singleton and 29 multiple pregnancies, were identified in mothers aged 50 and up. The highest frequency during this period was 6 per 100,000 deliveries. The prevalence for selected adverse outcomes in singleton pregnancies were: intrauterine fetal death (IUFD) 6%, preeclampsia 4%, preterm delivery 14%, gestational diabetes 8% and cesarean delivery 50%. In multiple pregnancies, the respective prevalence were: IUFD 2%, preeclampsia 22%, preterm delivery 57%, gestational diabetes 10% and cesarean delivery 79%. Pregnancy after assisted reproductive technologies was frequent (29% of singleton and 50% of multiple pregnancies). Conclusions This study found high frequency of obstetric and neonatal complications at extremely advanced maternal age. Despite a high prevalence of stillbirth in singleton pregnancies in the studied Nordic countries, other complications were less frequent than those previously reported in different populations. Adequate preconception consultation concerning maternal and neonatal hazards is highly recommended in this group of women.

Study question: Among babies born by ART, do singleton survivors of a vanishing twin have lower birth weight than other singletons? Summary answer: Vanishing-twin syndrome was associated with lower birth weight among ART singletons; a sibship analysis indicated that the association was not confounded by maternal characteristics that remain stable between deliveries. What is known already known: Previous studies indicate that ART singletons with vanishing-twin syndrome have increased risk of adverse pregnancy outcomes, compared with other ART singletons. The potential contribution of unmeasured maternal background characteristics has been unclear. Study design, size and duration: This was a Norwegian population-based registry study, including 17,368 mothers with 20,410 ART singleton deliveries between January 1984 and December 2013.Participants/materials, setting, methods: The study population included 17,291 ART singletons without vanishing-twin syndrome, 638 ART singletons with vanishing-twin syndrome, and 2,418 ART singletons with uncertain vanishing-twin status. We estimated differences in birth weight and gestational age comparing ART singletons with vanishing-twin syndrome first to all ART singletons without vanishing-twin syndrome, and subsequently to their ART siblings without vanishing-twin syndrome, using random- and fixed-effects linear regression, respectively. The corresponding comparisons for the associations with preterm birth and small-for-gestational age (SGA) were conducted using random-and fixed-effects logistic regression. The sibling analysis of preterm birth included 587 discordant siblings, while the sibling analysis of SGA included 674 discordant siblings.Main results and the role of chance: ART singletons with vanishing-twin syndrome had lower birth weight when compared to all ART singletons without vanishing-twin syndrome, with an adjusted mean difference (95% CI) of -116 grams (-165, -67). When we compared ART singletons with vanishing-twin syndrome to their ART singletons sibling without vanishing-twin syndrome, the adjusted mean difference was -112 grams (-209, -15). ART singletons with vanishing-twin syndrome also had increased risk of being born SGA, with an adjusted odds ratio (95% CI) of 1.48 (1.07, 2.03) compared to all ART singletons without vanishing twin-syndrome, and 2.79 (1.12, 6.91) in the sibship analyses. ART singletons with vanishing-twin syndrome were also more likely to be born preterm, although this difference did not reach statistical significance.Limitations, reasons for caution: We did not have information on maternal socio-economic status, but this factor is accounted for in the sibship analyses. We have no information on whether fresh or frozen embryos were replaced.Wider implications of the findings: The reduction in birth weight and increased SGA in ART singletons with vanishing-twin syndrome may suggest the presence of harmful intrauterine factors with long-term health impact. While vanishing twins are not routinely observed in naturally conceived pregnancies, loss of a twin is potentially a risk factor for the surviving fetus in any pregnancy. This could be further explored in large samples of naturally conceived pregnancies with the necessary information. Study funding/competing interest(s): The authors of this study are supported in part by the UK Medical Research Council, US National Institute of Environmental Health Sciences, and the Norwegian Research Council. The authors have no conflicts of interest.

Objectives To estimate the burden of miscarriage in the Norwegian population and to evaluate the associations with maternal age and pregnancy history. Design Prospective register based study. Setting Medical Birth Register of Norway, the Norwegian Patient Register, and the induced abortion register. Participants All Norwegian women that were pregnant between 2009-13. Main outcome measure Risk of miscarriage according to the woman’s age and pregnancy history estimated by logistic regression. Results There were 421 201 pregnancies during the study period. The risk of miscarriage was lowest in women aged 25-29 (10%), and rose rapidly after age 30, reaching 53% in women aged 45 and over. There was a strong recurrence risk of miscarriage, with age adjusted odds ratios of 1.54 (95% confidence interval 1.48 to 1.60) after one miscarriage, 2.21 (2.03 to 2.41) after two, and 3.97 (3.29 to 4.78) after three consecutive miscarriages. The risk of miscarriage was modestly increased if the previous birth ended in a preterm delivery (adjusted odds ratio 1.22, 95% confidence interval 1.12 to 1.29), stillbirth (1.30, 1.11 to 1.53), caesarean section (1.16, 1.12 to 1.21), or if the woman had gestational diabetes in the previous pregnancy (1.19, 1.05 to 1.36). The risk of miscarriage was slightly higher in women who themselves had been small for gestational age (1.08, 1.04 to 1.13). Conclusions The risk of miscarriage varies greatly with maternal age, shows a strong pattern of recurrence, and is also increased after some adverse pregnancy outcomes. Miscarriage and other pregnancy complications might share underlying causes, which could be biological conditions or unmeasured common risk factors.

Due to a low level of understanding of mechanisms involved in spontaneous preterm delivery there is a lack of reliable biomarkers. Existing biomarkers have a low positive predictive value but a high negative predictive value. Use of tests with high negative predictive value will reduce unnecessary interventions and hospitalization of women with threatening preterm delivery. When given to the right pregnant women, antenatal corticosteroid treatment are still the most important obstetrical intervention and reduces both neonatal mortality and short- and long-term morbidity.Several ongoing national Swedish multicenter studies may increase the understanding of the roles of cervical length, preeclampsia screening and magnesium sulfate dosage in the context of preterm delivery in a Nordic setting. Major development has been achieved in prediction and prevention of preterm preeclampsia at the cost of a 10% screen positive rate.

Background Pregnant women who request a cesarean section in the absence of obstetric indication have become a highly debated issue in academic as well as popular literature. In order to find adequate, targeted treatment and preventive strategies, we need a better understanding of this phenomenon. The aim of this study is to provide a qualitative exploration of maternal requests for a planned cesarean section in Norway, in the absence of obstetric indications. Methods A descriptive qualitative study was conducted consisting of 17 semi-structured, in-depth interviews with women requesting cesarean section and six focus group discussions with 20 caregivers (nine midwives, 11 obstetricians) working at a university hospital in Norway. Data were analyzed with Systematic Text Condensation, a method for thematic cross-case analysis. Results Fear of birth emerged most commonly as a result of a previous traumatic birth experience that prompted a preference for a planned cesarean to avoid a repetition of the trauma. For some women in our study, postnatal care and the puerperal period were their crucial past experiences, and giving birth by planned cesarean was seen as a way to ensure mental rather than physical capability to care for the expected child after birth. Others were under the impression of being at high risk for an emergency C-section, and requesting a planned one was based on their perceived risk. Such perceptions included having a narrow pelvis, hereditary factors or previous birth outcomes. Some primiparas requested a planned cesarean based on a deep-seated fear since their early teens, accompanied by alienation towards the idea of giving birth. Some obstetricians participating in our study also experienced requests that lacked what they regarded as any well-grounded reason or significant fear. Conclusions Behind a maternal request for a planned cesarean section are various rationales and life experiences needing carefully targeted attention and health care. Previous births are an important driver; thus, maternally requested cesareans should be regarded partly as an iatrogenic problem. Electronic supplementary material The online version of this article (10.1186/s12884-019-2250-6) contains supplementary material, which is available to authorized users.

Interview guide for in-depth interviews with women. Questions and probes used in interviews with women. (DOCX 15 kb)

Interview guide for focus group discussions with caregivers. Questions and probes used in focus group discussions with caregivers. (DOCX 14 kb)

Objective This study aimed to explore women's access to patient-centered counseling for concerns initiating cesarean requests in absence of obstetric indications in pregnancy, and to identify tensions, barriers and facilitators affecting such care. Design, setting and informants This qualitative study (June 2016 to August 2017) obtained data through semi-structured in-depth interviews with 17 women requesting planned C-section during birth counseling at a university hospital in Norway and focus group discussions with 20 caregivers (9 midwives and 11 obstetricians) employed at the same hospital. Analysis was carried out by systematic text condensation, a method for thematic analysis in medical research, presented within the frames of Levesque and colleagues’ conceptual framework of access to patient-centered care. Findings The analysis revealed that there were considerable tensions in care seeking and provision of counseling for maternal requests for C-section. There was a prominent culture of vaginal delivery among caregivers and women. The appropriateness of CS on maternal request was debated and caregivers revealed diverging attitudes and practices when agreement with women was not reached. Women's views on their entitlement to choose were divided, but the majority of women did not support complete maternal choice. Midwife-led counseling were highly appreciated among woman as well as obstetricians. Implications for practice Tensions and barriers in care seeking and provision of counseling for women requesting C-section for non-obstetric reasons, call for standardized counseling in order for equal and adequate care to be provided across health care institutions and providers. Dialogue-based decision-making and midwife-led care may improve satisfaction of care, enhance spontaneous vaginal deliveries and avoid future conflicts.

Background Gestational age estimation by last menstrual period (LMP) vs. ultrasound (or best obstetric estimate in the US) may result in discrepant classification of preterm vs. term birth. We investigated whether such discrepancies are associated with adverse infant outcomes. Methods We studied singleton livebirths in the Medical Birth Registries of Norway, Sweden and Finland and US live birth certificates from 1999 to the most recent year available. Risk ratios (RR) with 95% confidence intervals (CI) by discordant and concordant gestational age estimation for infant, neonatal and post-neonatal mortality, Apgar score

Background Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy. Citation Verner MA, Loccisano AE, Morken NH, Yoon M, Wu H, McDougall R, Maisonet M, Marcus M, Kishi R, Miyashita C, Chen MH, Hsieh WS, Andersen ME, Clewell HJ III, Longnecker MP. 2015. Associations of perfluoroalkyl substances (PFAS) with lower birth weight: an evaluation of potential confounding by glomerular filtration rate using a physiologically based pharmacokinetic model (PBPK). Environ Health Perspect 123:1317–1324; http://dx.doi.org/10.1289/ehp.1408837

Importance Clinicians have been urged to delay the use of obstetric interventions (eg, labor induction, cesarean delivery) until 39 weeks or later in the absence of maternal or fetal indications for intervention. Objective To describe recent trends in late preterm and early term birth rates in 6 high-income countries and assess association with use of clinician-initiated obstetric interventions. Design Retrospective analysis of singleton live births from 2006 to the latest available year (ranging from 2010 to 2015) in Canada, Denmark, Finland, Norway, Sweden, and the United States. Exposures Use of clinician-initiated obstetric intervention (either labor induction or prelabor cesarean delivery) during delivery. Main Outcomes and Measures Annual country-specific late preterm (34-36 weeks) and early term (37-38 weeks) birth rates. Results The study population included 2 415 432 Canadian births in 2006-2014 (4.8% late preterm; 25.3% early term); 305 947 Danish births in 2006-2010 (3.6% late preterm; 18.8% early term); 571 937 Finnish births in 2006-2015 (3.3% late preterm; 16.8% early term); 468 954 Norwegian births in 2006-2013 (3.8% late preterm; 17.2% early term); 737 754 Swedish births in 2006-2012 (3.6% late preterm; 18.7% early term); and 25 788 558 US births in 2006-2014 (6.0% late preterm; 26.9% early term). Late preterm birth rates decreased in Norway (3.9% to 3.5%) and the United States (6.8% to 5.7%). Early term birth rates decreased in Norway (17.6% to 16.8%), Sweden (19.4% to 18.5%), and the United States (30.2% to 24.4%). In the United States, early term birth rates decreased from 33.0% in 2006 to 21.1% in 2014 among births with clinician-initiated obstetric intervention, and from 29.7% in 2006 to 27.1% in 2014 among births without clinician-initiated obstetric intervention. Rates of clinician-initiated obstetric intervention increased among late preterm births in Canada (28.0% to 37.9%), Denmark (22.2% to 25.0%), and Finland (25.1% to 38.5%), and among early term births in Denmark (38.4% to 43.8%) and Finland (29.8% to 40.1%). Conclusions and Relevance Between 2006 and 2014, late preterm and early term birth rates decreased in the United States, and an association was observed between early term birth rates and decreasing clinician-initiated obstetric interventions. Late preterm births also decreased in Norway, and early term births decreased in Norway and Sweden. Clinician-initiated obstetric interventions increased in some countries but no association was found with rates of late preterm or early term birth.

Breastfeeding (BF) has been reported to improve long-term maternal metabolic health in observational studies, but not in the randomised controlled PROBIT study. Research also suggests that maternal pre-pregnant metabolic health may affect BF. We aimed to disentangle effects of BF on long-term maternal metabolic health from effects of pre-pregnant metabolic health on BF duration and long-term metabolic health.Longitudinal population-based cohort study.Nord-Trøndelag county, Norway.Women with a first live-born baby (1987-2008) participating in the Nord-Trøndelag Health Study (HUNT).Odds ratios (ORs) for short BF duration (3 months) by pre-pregnant body mass index (BMI), waist circumference (WCF), blood pressures (BPs), and heart rate (HR) were adjusted for age and smoking using logistic regression. Mixed linear models were used to estimate effects of BF duration (3, 3-6,6 months) on mean values of metabolic health parameters from baseline to follow-up.Mean change in BMI, WCF, BPs, HR, serum-glucose, and serum-lipids from baseline to follow-up by BF duration categories.We analysed 1403 women with a median follow-up of 12 years (interquartile range 11-22). Pre-pregnant WCF and HR correlated inversely with BF duration. Pre-pregnant BMI had a u-shaped correlation-pattern with BF duration. We observed similar between-group differences in metabolic health parameters at baseline and at follow-up, which implies that mean change in metabolic health parameters was similar across BF groups. Those women who started out with the best health had the longest BF duration and ended up with the best health, and those women who started out with the poorest health had shortest BF duration and ended up with the poorest health.Our results do not support a causal relationship between long BF duration and improved metabolic health. It is more likely that pre-pregnant metabolic health affects both BF duration and long-term metabolic health. Reverse causality can explain previously observed improved long-term metabolic health after BF.Breastfeeding seems not to affect long-term maternal metabolic health, but good pre-pregnant metabolic health does.

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.

OBJECTIVES: To explore international differences in the classification of births at extremely low gestation and the subsequent impact on the calculation of survival rates. METHODS: We used national data on births at 22 to 25 weeks’ gestation from the United States (2014; n = 11 144), Canada (2009–2014; n = 5668), the United Kingdom (2014–2015; n = 2992), Norway (2010–2014; n = 409), Finland (2010–2015; n = 348), Sweden (2011–2014; n = 489), and Japan (2014–2015; n = 2288) to compare neonatal survival rates using different denominators: all births, births alive at the onset of labor, live births, live births surviving to 1 hour, and live births surviving to 24 hours. RESULTS: For births at 22 weeks’ gestation, neonatal survival rates for which we used live births as the denominator varied from 3.7% to 56.7% among the 7 countries. This variation decreased when the denominator was changed to include stillbirths (ie, all births [1.8%–22.3%] and fetuses alive at the onset of labor [3.7%–38.2%]) or exclude early deaths and limited to births surviving at least 12 hours (50.0%–77.8%). Similar trends were seen for infants born at 23 weeks’ gestation. Variation diminished considerably at 24 and 25 weeks’ gestation. CONCLUSIONS: International variation in neonatal survival rates at 22 to 23 weeks’ gestation diminished considerably when including stillbirths in the denominator, revealing the variation arises in part from differences in the proportion of births reported as live births, which itself is closely connected to the provision of active care.

Objectives To estimate the risk of hypertensive pregnancy complications in women with epilepsy, with and without antiepileptic drugs, and assess the risk associated with the four most common antiepileptic drugs. Design A population-based cohort study using linked data from the Medical Birth Registry of Norway and the Norwegian Prescription Database. Women with epilepsy with and without antiepileptic drugs were compared with women without epilepsy. Setting Norway, 2004–2012. Participants All first pregnancies of women with epilepsy and women without epilepsy were included. Primary and secondary outcome measures Main outcome measures were hypertensive pregnancy complications: a compound variable of any hypertensive disorder, gestational hypertension, mild pre-eclampsia, severe pre-eclampsia, early onset pre-eclampsia, eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). Results In total, 1778 pregnancies in women with epilepsy and 221 662 in women without epilepsy were analysed. 682 of the women with epilepsy used antiepileptic drugs, the most common in monotherapy being: lamotrigine (n=280), carbamazepine (n=94), levetiracetam (n=71) and valproate (n=51). There was an increased risk of any hypertensive disorder in women with epilepsy (adjusted OR (aOR) 1.2, 95% CI 1.0 to 1.5) and in the subcategory using valproat (aOR 2.9, 95% CI 1.3 to 6.4). The most frequent hypertensive complication was mild pre-eclampsia and the risk was increased in women with epilepsy (aOR 1.4, 95% CI 1.1 to 1.8) and women with epilepsy with valproat (aOR 3.3, 95% CI 1.2 to 9.4). Conclusions Women with epilepsy have an increased risk of mild pre-eclampsia, but not for the severe types of hypertensive pregnancy complications. Lamotrigine and levetiracetam do not predispose for mild pre-eclampsia, whereas valproate was associated with an increased risk of mild pre-eclampsia.

Immunological mechanisms underlying the development of preeclampsia are well known, but no association to allergy has yet been demonstrated. The aim of this study was to assess the correlation between maternal pre-gestational allergy, and early-onset and late-onset preeclampsia, respectively. It was a retrospective cohort study including all women giving birth in the Norwegian cities of Stavanger (1996-2014) and Bergen (2009-2014). Pre-gestational asthma, allergy, other known risk factors for preeclampsia, maternal age and parity were obtained from the electronic medical record system. The main outcome variables were early-onset and late-onset preeclampsia (before and after 34 completed weeks of gestation, respectively). We used multinomial logistic regression to estimate odds ratios (OR) with 95% confidence intervals (95% CI) for early and late-onset preeclampsia in women with pre-gestational allergy when compared to women without allergy, adjusting for covariates. Predicted probabilities for the outcomes were also calculated. Of the 110 064 included pregnancies, 2 799 developed late-onset preeclampsia (2.5%) and 348 developed early-onset preeclampsia (0.3%). Pre-gestational allergy increased the risk of early-onset preeclampsia (OR 1.7, 95% CI 1.3-2.4), and reduced the risk of late-onset preeclampsia (OR 0.8, 95% CI 0.7-0.9). These findings add valuable information on preeclampsia as an immunological complication of pregnancy and corroborate the understanding of early- and late-onset preeclampsia as two different entities.