Increasing prevalence of cerebral palsy in children born very preterm in Denmark.

AIM: To analyse the rising prevalence of cerebral palsy (CP) in children born preterm in Denmark. METHOD: We included all live-born children born preterm in Denmark from 1997 to 2013. The prevalence of CP in children born preterm was categorized by gestational age and correlated with neonatal mortality and changes in clinical factors. RESULTS: Among 70 876 children, 824 (1.2%) had CP. The overall CP prevalence in children born preterm decreased substantially until 2001, from when it increased annually by 2.8% (95% confidence interval 0.6-5.0). When categorized, the prevalence only increased significantly in children born very preterm (gestational weeks 28-31). Neonatal mortality rates decreased steadily at all gestational ages during the entire study period. Clinical factors that changed during the study period were increasing numbers of high-risk pregnancies, maternal obesity, emergency caesarean sections, neonatal admissions, and usage of assisted ventilation. INTERPRETATION: The increasing prevalence of CP in children born preterm was driven by the subgroup born very preterm and matched their decrease in neonatal mortality. In similar population studies, decreased mortality was not followed by increased CP prevalence. An increase in clinical risk factors was unlikely to explain our findings, but more active neonatal life support may have played a role.

Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage.

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 genes HAND2, TBX3 and RAP2C/FRMD7 at 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.

Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: a nationwide cohort study.

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.

Maternal outcomes of planned mode of delivery for term breech in nulliparous women.

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.

Early suppression policies protected pregnant women from COVID-19 in 2020: A population-based surveillance from the Nordic countries.

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.

Incidence of shoulder dystocia and risk factors for recurrence in the subsequent pregnancy-A historical register-based cohort study.

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.

Validation of Obstetric Diagnosis and Procedure Codes in the Danish National Patient Registry in 2017.

Purpose: This study aimed to systematically evaluate the validity of variables related to pregnancy, delivery, and key characteristics of the infant in the Danish National Patient Register using maternal medical records as the reference standard. Patients and Methods: We reviewed medical records of 1264 women giving birth in the Region of Southern Denmark during 2017. We calculated positive (PPV) and negative (NPV) predictive values, sensitivity, and specificity to estimate the validity of 49 selected variables. Results: The PPV was ≥0.90 on most pregnancy-related variables including parity, pre-gestational BMI, diabetes disorders, and previous cesarean section, while it was lower for hypertensive disorders, especially mild to moderate preeclampsia (0.49, 95% CI 0.32-0.66). Sensitivity ranged from 0.80 to 1.00 on all pregnancy-related variables, except hypertensive disorders (sensitivity 0.38-0.71, lowest for severe preeclampsia). On most delivery-related variables including obstetric surgical procedures (eg cesarean section and induction of labor), pharmacological pain-relief, and gestational age at delivery, PPV's ranged from 0.98 to 1.00 and the corresponding sensitivities from 0.87 to 1.00. Regarding infant-related variables, both the APGAR score registered five minutes after delivery and birthweight yielded a PPV of 1.00. Conclusion: Obstetric coding in the Danish National Patient Register shows very high validity and completeness making it a valuable source for epidemiologic research.

Placental weight percentile curves in a Danish population.

INTRODUCTION: The role of the placenta is to transport oxygen and nutrients to the fetus, and a well-functioning placenta is vital to fetal health. Our aim was to develop placental weight percentile curves adjusted by gestational age, and stratified by major maternal comorbidities. MATERIAL AND METHODS: The study was a population study in a Danish cohort. Data was drawn from The Medical Birth Register and the National Patient Register. We included singleton births with a gestational age of 22 + 0 to 42 + 6 weeks. We excluded multiple pregnancies, stillbirths and retained placentas. A total of 611 418 placentas were included. Percentile line graphs were created in groups of all placentas, hypertensive disorders and diabetic disorders. RESULTS: Tables and figures are presented for placental weight percentile curves according to gestational age for all placentas, hypertensive disorders and diabetic disorders, respectively. Placental weight was generally higher in the diabetic placentas, and lower in the hypertensive placentas. CONCLUSIONS: These percentile curves may serve as a reference for other populations, and may be useful for other studies investigating the role of the placenta in relation to pregnancy outcomes, and health in later life.

Winter, spring, summer or fall: temporal patterns in placenta-mediated pregnancy complications-an exploratory analysis.

PURPOSE: Placenta-mediated pregnancy complications, like growth restriction and hypertensive disorders, are leading causes of maternal, fetal and neonatal morbidity and mortality in high-income countries. The purpose was to investigate if there is a seasonal variation in placenta-mediated pregnancy complications (small for gestational age, intrauterine growth restriction, preeclampsia, preterm birth and intrauterine fetal death). METHODS: This is a Danish cohort study including all singleton deliveries at gestational week 22 up to and including week 41 conceived from December 2006 to November 2016 (N = 555,459). We used statistical process control charts to visualize data and to test for patterns of non-random variation in data over time for pregnancies with risk factors (BMI, diabetes, in vitro fertilization, maternal age > 40 years, primipara, previous caesarean and smoking) and each of the following outcome: fetal growth restriction, hypertensive disorders, preterm birth and intrauterine fetal death. The study was approved by the Danish Data Protection agency; REG-039-2019. RESULTS: We found a seasonal pattern in hypertensive disorders during pregnancy with dips in pregnancies conceived in the fall season and highest risk by conception in the spring and summer season. We found no apparent seasonality in cases of preterm delivery, small for gestational age and intrauterine mortality. Individual risk factors (e.g. smoking and obesity) for placenta-mediated complicated over time were in consistency with the general trends. CONCLUSIONS: We found a significant seasonal variation in the risk of hypertensive disorders of pregnancy with highest risk by conception in the spring and summer season. This study found no seasonal variation in other placenta-mediated complications.

Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage.

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 severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes, HAND2, TBX3, and RAP2C/FRMD7, at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status.

The impact of the COVID-19 lockdown on birthweight among singleton term birth in Denmark.

In Denmark, a nationwide COVID-19 lockdown was implemented on March 12, 2020 and eased on April 14, 2020. The COVID-19 lockdown featured reduced prevalence of extremely preterm or extremely low birthweight births. This study aims to explore the impact of this COVID-19 lockdown on term birthweights in Denmark. We conducted a nationwide register-based cohort study on 27,870 live singleton infants, born at term (weeks 37-41), between March 12 and April 14, 2015-2020, using data from the Danish Neonatal Screening Biobank. Primary outcomes, corrected for confounders, were birthweight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA), comparing the COVID-19 lockdown to the previous five years. Data were analysed using linear regression to assess associations with birthweight. Multinomial logistic regression was used to assess associations with relative-size-for-gestational-age (xGA) categories. Adjusted mean birthweight was significantly increased by 16.9 g (95% CI = 4.1-31.3) during the lockdown period. A dip in mean birthweight was found in gestational weeks 37 and 38 balanced by an increase in weeks 40 and 41. The 2020 lockdown period was associated with an increased LGA prevalence (aOR 1.13, 95% CI = 1.05-1.21). No significant changes in proportions of xGA groups were found between 2015 and 2019. The nationwide COVID-19 lockdown resulted in a small but significant increase in birthweight and proportion of LGA infants, driven by an increase in birthweight in gestational weeks 40 and 41.

Women's experiences of induction of labour with misoprostol tablets compared with vaginal insert.

INTRODUCTION: The aim of this study was to compare nulliparous women's experiences with induction of labour using two different regimens of misoprostol. METHODS: We adapted a validated questionnaire regarding experience with induced labour. In two different hospitals, 123 women undergoing medical induction of labour completed a questionnaire after delivery. An independent-samples T-test was used for comparison of parametric continuous variables and Pearson's χ2 test was used for categorical data. The two groups differed regarding BMI and pregnancy complications. No adjusted estimates were calculated. RESULTS: Women induced with oral misoprostol experienced more painful induction of labour (p = 0.019) and described feeling that their length of stay at hospital was excessive (p = 0.028). Overall, the experience of giving birth after induction of labour was reported as "good" among 87.8% of women induced with oral misoprostol compared with 72.7% of the women induced with a slow-release misoprostol vaginal insert (p = 0.039). CONCLUSION: In two departments characterized by several differences, including whether vaginal or oral misoprostol was used, induction with oral misoprostol in an out-patient setting was associated with a better experience of labour than induction with a slow-release misoprostol vaginal insert. FUNDING: Region Zealand Health Scientific Research Foundation supported the study financially. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov ID: NCT02693587 on 26 February 2016 and with EudraCT number 2020-000366-42 on 23 January 2020 (retrospectively registered).

Severe COVID-19 during pregnancy in Sweden, Norway, and Denmark.

INTRODUCTION: Pregnancy is a risk factor for severe coronavirus disease 2019 (COVID-19) and adverse pregnancy outcomes. We aimed to explore maternal characteristics, pregnancy outcomes, vaccination status, and virus variants among pregnant women admitted to intensive care units (ICU) with severe COVID-19. MATERIAL AND METHODS: We identified pregnant women admitted to ICU in Sweden (n = 96), Norway (n = 31), and Denmark (n = 16) because of severe COVID-19, from national registers and clinical databases between March 2020 and February 2022 (Denmark), August 2022 (Sweden), or December 2022 (Norway). Their background characteristics, pregnancy outcome, and vaccination status were compared with all birthing women and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test-positive pregnant women during the same time period. We calculated the number admitted to ICU per 10 000 birthing and per 1000 SARS-CoV-2 test-positive women during the Index, Alpha, Delta, and Omicron periods. RESULTS: Women admitted to ICU had a higher mean body mass index, were more often of non-Scandinavian origin, had on average lower education and income levels, had a higher proportion of chronic and pregnancy-related conditions, delivered preterm, had neonates with low Apgar scores, and had more infants admitted to neonatal care, compared with all birthing and test-positive pregnant women. Of those admitted to ICU, only 7% had been vaccinated before admission. Overall, the highest proportion of women admitted to ICU per birthing was during the Delta period (4.1 per 10 000 birthing women). In Norway, the highest proportion admitted to ICU per test-positive pregnant women was during the Delta period (17.8 per 1000 test-positive), whereas the highest proportion of admitted per test-positive in Sweden and Denmark was seen during the Index period (15.4 and 8.9 per 1000 test-positive, respectively). CONCLUSIONS: Admission to ICU because of COVID-19 in pregnancy was a rare event in the Scandinavian countries, but women who were unvaccinated, of non-Scandinavian origin, and with lower socio-economic status were at higher risk of admission to ICU. In addition, women admitted to ICU for COVID-19 had higher risk of adverse pregnancy outcomes.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Breech delivery in low-income settings: A systematic review of perinatal and maternal outcomes in vaginal versus cesarean breech deliveries.

Most studies comparing vaginal breech delivery (VBD) with cesarean breech delivery (CBD) have been conducted in high-income settings. It is uncertain whether these results are applicable in a low-income setting. To assess the neonatal and maternal mortality and morbidity for singleton VBD compared to CBD in low- and lower-middle-income settings,the PubMed database was searched from January 1, 2000, to January 23, 2020 (updated April 21, 2021). Randomized controlled trials (RCTs) and non-RCTs comparing singleton VBD with singleton CBD in low- and lower-middle-income settings reporting infant mortality were selected. Two authors independently assessed papers for eligibility and risk of bias. The primary outcome was relative risk of perinatal mortality. Meta-analysis was conducted on applicable outcomes. Eight studies (one RCT, seven observational) (12 510 deliveries) were included. VBD increased perinatal mortality (relative risk [RR] 2.67, 95% confidence interval [CI] 1.82-3.91; one RCT, five observational studies, 3289 women) and risk of 5-minute Apgar score below 7 (RR 3.91, 95% CI 1.90-8.04; three observational studies, 430 women) compared to CBD. There was a higher risk of hospitalization and postpartum bleeding in CBD. Most of the studies were deemed to have moderate or serious risk of bias. CBD decreases risk of perinatal mortality but increases risk of bleeding and hospitalization.

The magnitude rather than the rate of decline in fetal growth is a stronger risk factor for perinatal mortality in term infants.

BACKGROUND: Prenatal diagnosis of an infant suspected of having fetal growth restriction is important because of its strong association with perinatal mortality and morbidity. The current Delphi consensus criteria include a decline of >50th percentiles in fetal growth when diagnosing late fetal growth restriction; however, the evidence underpinning this criterion is limited. OBJECTIVE: This study aimed to analyze the relationships among the magnitude of decline in fetal growth and stillbirth, perinatal mortality, and adverse neonatal outcomes. STUDY DESIGN: This cohort study of 15,861 pregnancies was conducted at the Mater Mother's Hospital in Brisbane, Australia. The decline in fetal growth was calculated as a drop in either estimated fetal weight or abdominal circumference percentiles between 2 ultrasound scans performed after 18 weeks of gestation. Relationships between declining fetal growth and the outcomes were, firstly, analyzed as a continuous variable and, if significant, further assessed with the rate of decline and different magnitudes of decline, compared to the referent category (change in growth of ±10 percentiles between scans). The 3 categories of growth decline were >10th to <25th percentiles, ≤25th to <50th percentiles, and ≥50th percentiles. Associations were analyzed by logistic regressions. The primary study outcomes were stillbirth and perinatal mortality (composite of stillbirth and neonatal death). The secondary outcomes were birth of a small-for-gestational-age infant (birthweight of <10th percentile for gestation), emergency cesarean delivery for nonreassuring fetal status, and composite severe neonatal morbidity. RESULTS: The risks of stillbirth and perinatal mortality increased significantly by 2.6% (0.4%-4.6%) and 2.8% (1.0%-4.5%), respectively, per 1 percentile decline in fetal growth. In addition, the odds of stillbirth (adjusted odds ratio, 3.68 (1.32-10.24) and perinatal mortality (4.44) (1.82-10.84)) compared to the referent group were significantly increased only when the decline was ≥50th percentiles, regardless of birthweight. Furthermore, none of the primary outcomes were significantly associated with the rate of growth decline. The risk of a small-for-gestational-age infant increased by 2.4% (2.2%-2.7%) for every percentile decline. Conversely, reduced fetal growth was not associated with emergency cesarean delivery for nonreassuring fetal status or severe neonatal morbidity. CONCLUSION: Our results supported the use of a ≥50th percentile decline in fetal growth as a criterion for identifying infants at risk of late fetal growth restriction. This cutoff also identified fetuses at high risk of perinatal mortality, regardless of birthweight and rate of growth decline. Our findings may guide obstetrical practice by alerting clinicians to the importance of incorporating the magnitude of fetal growth decline into antenatal counseling and decisions regarding the timing of birth.

Intravenous ferric derisomaltose versus oral iron for persistent iron deficient pregnant women: a randomised controlled trial.

PURPOSE: To compare the efficacy of intravenous (IV) iron (ferric derisomaltose) with oral iron (ferrous fumarate) in women 14-21 weeks pregnant with persistent iron deficiency (ferritin < 30 µg/L). METHODS: In a single-centre, open-label, randomised controlled trial at a Danish hospital, women with persistent iron deficiency after routine oral iron treatment were allocated to receive 1000 mg IV iron (single-dose) or 100 mg elemental oral iron daily. Outcomes were assessed during an 18-week follow-up period. The primary endpoint was the proportion of non-anaemic (haemoglobin [Hb] ≥ 11 g/dL) women throughout follow-up. Other outcomes included changes in haematological parameters, patient-reported fatigue, and quality of life (QoL). Safety was assessed by recording adverse events. RESULTS: From July 2017 to February 2020, 100 women were randomised to IV iron and 101 to oral iron. Throughout follow-up, 91% of women were non-anaemic in the IV iron group compared with 73% in the oral iron group (18% difference [95% confidence interval 0.10-0.25]; p < 0.001). The mean Hb increase was significantly greater with IV iron versus oral iron at Weeks 6 (0.4 versus - 0.2 g/dL; p < 0.001), 12 (0.5 versus 0.1 g/dL; p < 0.001), and 18 (0.8 versus 0.5 g/dL; p = 0.01). Improvements in fatigue and QoL were greater with IV iron versus oral iron at Weeks 3 and 6. The incidence of treatment-related adverse events was comparable between treatment groups. CONCLUSION: IV iron was superior in preventing anaemia compared with oral iron in pregnant women with persistent iron deficiency; biochemical superiority was accompanied by improved fatigue and QoL. CLINICAL TRIAL REGISTRATION: European Clinical Trials Database: EudraCT no.: 2017-000776-29 (3 May 2017); ClinicalTrials.gov: NCT03188445 (13 June 2017). The trial protocol has been published: https://dx.doi.org/10.1186%2Fs13063-020-04637-z .

Cardiotocography combined with ST analysis versus cardiotocography combined with fetal blood sampling in deliveries with abnormal CTG: a randomized trial.

PURPOSE: The aim was to investigate if intrapartum monitoring with cardiotocography (CTG) in combination with ST analysis (STAN) results in an improved perinatal outcome. METHODS: We performed a two-center randomized trial. 1013 women with term fetuses in cephalic presentation entered the trial. If a CTG showed intermediate or pathological abnormalities, they were offered fetal blood sampling (FBS) and inclusion if the pH value was above 7.25. They were randomized to either CTG + FBS or CTG + STAN. The primary outcome was neonatal metabolic acidosis, defined as umbilical cord arterial blood pH below 7.05, and base excess equal to or below -10. The secondary outcomes included operative vaginal delivery for fetal distress. RESULTS: The rate of metabolic acidosis was 0.8% in the CTG + FBS group and 1.5% in women in the CTG + STAN (P = 0.338). More women in the CTG + STAN group delivered by operative vaginal delivery (25.6% vs 33.5%, P = 0.006). Significantly fewer women in the CTG + STAN group had three to five (28.8% vs 11.0%, P = < 0.001) and six to ten fetal blood samples taken (3.4% vs 0.4%, P = < 0.001). CONCLUSION: CTG + STAN did not reduce the incidence of neonatal metabolic acidosis compared to CTG + FBS. CTG + STAN was, however, associated with an increased risk of operative vaginal delivery and a reduced use of FBS. If STAN is used for fetal surveillance, we recommend that it is combined with other methods, such as FBS, for confirmation of the need for operative delivery. CLINICALTRIALS: gov ID: NCT01699646. Date of registration: October 4, 2012 (retrospectively registered). https://clinicaltrials.gov/ct2/show/NCT01699646?id=NCT01699646&draw=2&rank=1.

Incidence of postpartum hemorrhage and risk factors for recurrence in the subsequent pregnancy.

PURPOSE: To assess incidence and risk factors for postpartum hemorrhage (PPH) and identify women at high risk of recurrence in the subsequent pregnancy. METHODS: This register-based study includes data on women from the Capital Region of Denmark with two consecutive deliveries recorded in the Copenhagen Obstetric Database from 2007 to 2020. PPH, defined as a blood loss of 1000 mL or more within 24 h after delivery, was the primary outcome measure. We calculated incidence and recurrence rate of PPH and assessed possible risk factors at index and subsequent deliveries. RESULTS: We included 44,800 women with 95,673 deliveries. The overall incidence of PPH was 6.3%. Women with previous PPH had a 3.5-fold increased risk of PPH in a subsequent delivery compared to unaffected women (19.1 vs. 5.4%; OR 4.1; 95% CI 3.7-4.5). Major risk factors for recurrence were PPH in combination with blood transfusion or manual removal of placenta at the index delivery. Labor induction in subsequent pregnancy increased the risk of recurrent PPH compared to spontaneous onset (OR 1.5; 95% CI 1.2-1.9), while planned caesarean section reduced the risk, compared to planned vaginal delivery (OR 0.6; 95% CI 0.4-0.7). CONCLUSION: Previous PPH increases the risk of PPH in subsequent pregnancy 3.5-fold. The risk of recurrent PPH increases with labor induction and decreases with planned caesarean section in the subsequent pregnancy. To prevent recurrent PPH, personalized counseling based on risk factors, relevant labor history and maternal preferences is suggested.