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.

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.

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.

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.

Gestational diabetes mellitus by maternal country of birth and length of residence in immigrant women in Norway.

AIMS: Immigrant women are at higher risk for gestational diabetes mellitus (GDM) than non-immigrant women. This study described the prevalence of GDM in immigrant women by maternal country of birth and examined the associations between immigrants' length of residence in Norway and GDM. METHODS: This Norwegian national population-based study included 192,892 pregnancies to immigrant and 1,116,954 pregnancies to non-immigrant women giving birth during the period 1990-2013. Associations were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models, adjusted for year of delivery, maternal age, marital status, health region, parity, education and income. RESULTS: The prevalence and adjusted OR [CI] for GDM were substantially higher in immigrant women from Bangladesh (7.4%, OR 8.38 [5.41, 12.97]), Sri Lanka (6.3%, OR 7.60 [6.71, 8.60]), Pakistan (4.3%, OR 5.47 [4.90, 6.11]), India (4.4%, OR 5.18 [4.30, 6.24]) and Morocco (4.3%, OR 4.35 [3.63, 5.20]) compared to non-immigrants (prevalence 0.8%). Overall, GDM prevalence increased from 1.3% (OR 1.25 [1.14, 1.36]) to 3.3% (OR 2.55 [2.39, 2.71]) after 9 years of residence in immigrants compared to non-immigrant women. This association was particularly strong for women from South Asia. CONCLUSIONS: Gestational diabetes mellitus prevalence varied substantially between countries of maternal birth and was particularly high in immigrants from Asian countries. GDM appeared to increase with longer length of residence in certain immigrant groups.

Quantitative User Data From a Chatbot Developed for Women With Gestational Diabetes Mellitus: Observational Study.

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.