Lone Krebs

Background: Smallness for gestational age and reduced head circumference at birth are consistently associated with later neurodevelopmental disorders (NDD), but it is unclear whether similar associations are present at foetal biometry in mid‐gestation. Objectives: To investigate associations between second‐trimester foetal biometric measurements and later NDD. Methods: We conducted a population‐based cohort study using data from routine second‐trimester ultrasound scans (gestational weeks 18–21) in Denmark. We included all singleton euploid live births from 2008 to 2015. Foetal biometrics included head circumference, biparietal diameter (BPD), abdominal circumference (AC), femur length, estimated foetal weight (EFW), and the head‐abdomen ratio. NDD comprised cerebral palsy (CP), epilepsy, intellectual disability, and autism spectrum disorders (ASD). Children were followed from birth until diagnosis, death, emigration, or 31 December 2022. Associations were examined using multivariable Cox proportional hazards models, and cumulative incidence through age 10 years was estimated accounting for death as a competing risk. Adjusted mean differences in biometric Z ‐scores were examined using multivariable linear regression. Results: Among 337,028 children, 13,414 (4.0%; 69.7% males) were diagnosed with at least one NDD. Larger BPD was associated with higher hazards of epilepsy, intellectual disability, and ASD. Larger AC and EFW were associated with lower hazard of intellectual disabilities. Individuals with epilepsy, ASD, and intellectual disabilities had slightly larger mean BPD Z ‐score at their second–trimester scans, compared to children without NDD. Furthermore, smaller HC was associated with lower hazards and cumulative incidence of epilepsy, whereas shorter FL was associated with higher hazards of CP and epilepsy. Conclusions: Mid‐gestation head size did not follow the expected risk pattern. These findings propose a rethinking of the relationship between restricted brain growth and neurodevelopmental impairment, suggesting that atypical early brain development may be reflected in accelerated rather than reduced growth, or that restricted growth‐related causes of NDD act later in pregnancy.

Introduction: Although perinatal death rates in the Nordic countries are among the lowest in the world, the risk of perinatal death is unevenly distributed across the Nordic countries, despite similarity in health care systems and pregnancy care. Birth registration practices across countries may explain some of the differences. We investigated differences in national registration of perinatal mortality within the Nordic countries and its impact on perinatal mortality according to gestational age.Material and Methods: Each country provided information by answering a questionnaire about registration of perinatal deaths. Furthermore, we collected aggregated count data based on Medical Birth Registries (MBR) from all Nordic countries in 2000 to 2021. Perinatal mortality was defined as stillbirth or neonatal death occurring within first 7 days of life. Data were grouped into six groups by gestational age (GA): extremely preterm (>28 + 0 weeks, subdivided into 22 + 0–23 + 6 and 24 + 0–27 + 6), very preterm (GA 28 + 0–31 + 6), moderate preterm (GA 32 + 0–33 + 6), late preterm (GA 34 + 0–36 + 6), term (GA 37 + 0–40 + 6) and late term or post‐term birth (GA ≥ 41 + 0). Perinatal mortality rate and risk ratio with 95% confidence intervals were calculated per country for each gestational age group. For Denmark, separate analyses included and excluded induced abortions.Results: The study included 6 343 805 live births, 22 727 stillbirths and 8932 liveborn infants who died within the first week of life after GA 22 + 0. Further 25 057 births were included with GA < 22 + 0, unknown GA and as a result of induced abortion. Overall, perinatal mortality rates decreased during year 2000–2021 in all Nordic countries. After exclusion of induced abortions, the perinatal mortality rate was similar in the five Nordic countries. The perinatal mortality rate for extremely preterm born infants was highest in Denmark, whereas the highest rate among infants born late term/post‐term was in Sweden.Conclusions: The perinatal mortality rate in the Nordic countries is still decreasing, especially in the group of extremely preterm born infants. This study supports the need for further standardization of birth registration practices to ensure the validity of international comparisons.

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal–fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genesHAND2,TBX3andRAP2C/FRMD7at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified.

Objective: To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs. Methods: A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. Data were retrieved from the Danish Foetal Medicine Database, which included both pre- and postnatal diagnoses of CHDs. Children or foetuses with chromosomal aberrations were excluded. Odds ratios were calculated with logistic regression models for CHDs overall, severe CHDs and five of the most prevalent subtypes of CHDs. Results: Of the 547 105 pregnancies included in the cohort, 5 442 had CHDs (1.0%). Risk of CHDs became gradually higher with higher maternal BMI; for BMI 25-29.9 kg/m², adjusted odds ratio (aOR) 1.17 (95% CI 1.10-1.26), for BMI 30-34.9 kg/m², aOR 1.21 (95% CI 1.09-1.33), for BMI 35-39.9 kg/m², aOR 1.29 (95% CI 1.11-1.50) and for BMI ≥ 40 kg/m², aOR 1.85 (95% CI 1.54-2.21). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 231), an association with maternal BMI ≥ 30 kg/m² was seen, OR 1.67 (95% CI 1.13-2.44). 109 654 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was associated with the risk of CHDs in the second pregnancy (BMI 2 to < 4 kg/m²: aOR 1.29, 95% CI 1.09-1.53; BMI ≥ 4 kg/m²: aOR 1.36, 95% CI 1.08-1.68). Conclusion: The risk of foetal CHDs became gradually higher with higher maternal BMI and interpregnancy weight increases above 2 BMI units were also associated with a higher risk of CHDs.

Objective: To estimate short- and long-term maternal complications in relation to planned mode of term breech delivery in first pregnancy. Design: Register-based cohort study Setting: Denmark Population: Nulliparous women with singleton breech delivery at term between 1991 and 2018 (n = 30,778). Methods: We used data from the Danish national health registries to identify nulliparous women with singleton breech presentation at term and their subsequent pregnancies. We performed logistic regression to compare the risks of maternal complications by planned mode of delivery. All data were proceeded and statistical analyses were performed in SAS 9.4 (SAS Institute Inc. Cary, NC, USA). Main outcome measures: Postpartum hemorrhage, operative complications, puerperal infections in first pregnancy and uterine rupture, placenta previa, post-partum hemorrhage, hysterectomy and stillbirth in the subsequent two pregnancies. Results: We identified 19,187 with planned cesarean and 9,681 with planned vaginal breech delivery of which 2,970 (30.7%) delivered vaginally. Planned cesarean significantly reduced the risk of postoperative infections (2.4% vs 3.9% adjusted odds ratio (aOR): 0.54 95% confidence interval (CI) 0.44–0.66) and surgical organ lesions (0.06% vs 0.1%; (aOR): 0.29 95% CI 0.11–0.76) compared to planned vaginal breech delivery. Planned cesarean delivery in the first pregnancy was associated with a significantly higher risk of uterine rupture in the subsequent pregnancies but not with risk of postpartum hemorrhage, placenta previa, hysterectomy, or stillbirth. Conclusion: Compared to planned vaginal breech delivery at term, nulliparous women with planned cesarean breech delivery have a significantly reduced risk of postoperative complications but a higher risk of uterine rupture in their subsequent pregnancies.

Introduction: Shoulder dystocia is a rare obstetric complication, and the risk of recurrence is important for planning future deliveries.Material and Methods: The objectives of our study were to estimate the incidence and risk factors for recurrence of shoulder dystocia and to identify women at high risk of recurrence in a subsequent vaginal delivery. The study design was a nationwide register‐based study including data from the Danish Medical Birth Registry and National Patient Register in the period 2007–2017. Nulliparous women with a singleton fetus in cephalic presentation were included for analysis of risk factors in index and subsequent delivery.Results: During the study period, 6002 cases of shoulder dystocia were reported with an overall incidence among women with vaginal delivery of 1.2%. Among 222 225 nulliparous women with vaginal births, shoulder dystocia complicated 2209 (1.0%) deliveries. A subsequent birth was registered in 1106 (50.1%) of the women with shoulder dystocia in index delivery of which 837 (77.8%) delivered vaginally. Recurrence of shoulder dystocia was reported in 60 (7.2%) with a six‐fold increased risk compared with women without a prior history of shoulder dystocia (risk ratio [RR] 5.70, 95% confidence interval [CI]: 4.41 to 7.38; adjusted RR 3.06, 95% CI: 2.03 to 4.68). Low maternal height was a significant risk factor for recurrence of shoulder dystocia. In the subsequent delivery, significant risk factors for recurrence were birthweight >4000 g, positive fetal weight difference exceeding 250 g from index to subsequent delivery, stimulation with oxytocin and operative vaginal delivery. In the subsequent pregnancy following shoulder dystocia, women who underwent a planned cesarean (n = 176) were characterized by more advanced age and a higher prevalence of diabetes in the subsequent pregnancy. Furthermore, they had more often experienced operative vaginal delivery, severe perineal lacerations, and severe neonatal complications at the index delivery.Conclusions: The incidence of shoulder dystocia among nulliparous women with vaginal delivery was 1.0% with a 7.2% risk of recurrence in a population where about 50% had a subsequent birth and of these 78% had subsequent vaginal delivery. Important risk factors for recurrence were low maternal height, increase of birthweight ≥250 g from index to subsequent delivery and operative vaginal delivery.

Introduction: The Coronavirus 2019 Disease (COVID‐19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13–17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID‐19‐related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic.Material and methods: This is a meta‐analysis of population‐based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1–December 31, 2020. Pregnant women with a positive SARS‐CoV‐2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID‐19‐related or non‐COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively.Results: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS‐CoV‐2 infection and 137 (22.8%) were admitted for COVID‐19 symptoms. The pooled incidence of COVID‐19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I² = 77.6, tau² = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries.Conclusions: There was a clear variation in pregnant women's risk of COVID‐19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta‐analysis indicates that early suppression policies protected pregnant women from severe COVID‐19 disease prior to the availability of individual protection with vaccines.