Search

Jane Bendix,1 Hanne Kristine Hegaard,2 Jens Langhoff-Roos,3 Thomas Bergholt3 1Department of Gynaecology and Obstetrics, Nordsjaellands Hospital Hillerod, University of Copenhagen, Hillerod, Denmark; 2The Research Unit of Women’s and Children’s Health, The Juliane Marie Centre for Women, Children and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 3Department of Obstetrics, The Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Purpose: Population-based studies evaluating the use and extent of antenatal obstetric hospitalizations (AOH) are sparse. The objective of the present study was to describe the prevalence, time trend, and risk factors for AOH in Denmark. Materials and methods: A retrospective national register-based cohort study was conducted that included all pregnancies with delivery after 22 gestational weeks in Denmark from 2003 to 2012. The outcomes were AOH and the diagnoses leading to these hospitalizations. AOH was defined as an antenatal hospitalization for at least 1 day with at least one obstetric International Classification of Diseases-10 diagnosis and admission date more than 3 days before delivery. Results: The study included 617,906 pregnancies; 48,366 (7.8%) pregnancies were associated with 64,072 AOH before delivery. The percentage of pregnancies with AOH decreased from 8.6% to 7.1%. The median length of stay decreased from 3 to 2 days, and admission for at least 7 days was almost halved. Threatened preterm delivery was the most frequent diagnostic category for AOH. A decline was seen in all diagnostic categories except maternal diseases. Significant risk factors for AOH were multiple pregnancies, low or high maternal age and body mass index, nulliparity, lower educational levels, unemployment or being outside the workforce, single partner status, and smoking. The relative risk of very preterm delivery before gestational age of 34 weeks was higher in pregnancies with AOH compared with pregnancies without AOH (relative risk 15.2; 95% confidence interval: 14.6–15.8). Conclusion: This study shows a shift toward less use and shorter duration of antenatal hospitalization in Denmark. The most common indication used in pregnancies with AOH was threatened preterm delivery, and more than one-third resulted in very preterm deliveries. Keywords: obstetric admissions, pregnancy complications, diagnosis, Danish health registry study, time trend

Objective: To study the effect of antenatal magnesium sulphate (MgSO4) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis. Design: Double‐blind, randomised, placebo‐controlled, multi‐centre trial. Setting: Fourteen Danish obstetric departments. Population: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children. Methods: Women were randomised to receive either a loading dose of 5 g MgSO4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire. Main outcome measure: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP. Results: The crude rates of moderate to severe CP in the MgSO4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23–1.65). Conclusions: Antenatal MgSO4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis. Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation. Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation. [ABSTRACT FROM AUTHOR]

Introduction: Growth Differentiation Factor 15 (GDF15) increases substantially during pregnancy and is primarily produced by the placenta. Elevated levels of GDF15 have been associated with mental health problems in non-perinatal populations, higher corticosterone levels, and decreased estrogen receptor activity. However, the role of GDF15 in mental health during the perinatal transition remains unknown. This longitudinal study is the first to evaluate pregnancy levels of GDF15 in cerebrospinal fluid (cGDF15), plasma (pGDF15) and placenta GDF15 mRNA, along with mapping plasma GDF15 (pGDF15) level changes from late pregnancy to early postpartum. Moreover, we aimed to evaluate the association between pregnancy cGDF15 levels and cortisol early postpartum, evaluate the association between pregnancy cGDF15 levels and mental health in pregnancy and postpartum, and evaluate the association between pGDF15 and estrogens and high-sensitivity C-reactive protein (CRP)., Methods: We included data from 95 women scheduled for a planned cesarean section and obtained cerebrospinal fluid (CSF) and plasma levels of GDF15. We quantified GDF15 mRNA levels in placenta biopsies. Estrogens, high-sensitivity CRP, and mental health measures were further collected on the day or one day before the cesarean section. At five weeks postpartum, mental health measures and saliva samples for cortisol analyses were collected. Correlation analyses for GDF15 in CSF, plasma, and placenta mRNA were performed, along with association analyses for pregnancy cGDF15, Cortisol Awakening Response, and mental health outcomes., Results: We demonstrated a strong correlation between cGDF15 and pGDF15 (r=0.52; p<0.001) and found that both cGDF15 and pGDF15 correlated with placenta GDF15 mRNA*placental weight (r=0.62, p<0.001 and r=0.44, p=0.008, respectively). During late pregnancy, both estradiol (E2) and estriol (E3) were significantly associated with pGDF15 levels (E2: p=0.002; E3: p(corrected)<0.001). Finally, we found that cGDF15 levels were not associated with self-reported mental well-being or the Cortisol Awakening Response or absolute cortisol at awakening postpartum., Conclusion: This novel study points to the unique hormonal landscape during the perinatal transition and the specific role of GDF15 in pregnancy, which appears uncoupled with perinatal mental health and cortisol outcomes. Our data also strongly imply that the overall amount of circulating GDF15 in late pregnancy is closely related to placenta size., Competing Interests: Declaration of Competing Interest VGF discloses that she has received honorarium in form of consulting fees from SAGE Therapeutics, Lundbeck Pharma A/S, Janssen Cilag A/S and Gedeon-Richter A/S. ABK and CC are co-founders of Ousia Pharma ApS. All other authors disclose no potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Female minipuberty is characterized by complex dynamics of circulating reproductive hormones, while the relationship between ovarian and uterine morphology and reproductive hormones remains to be elucidated., Aim: To investigate the association between reproductive hormones and ovarian as well as uterine morphology by transabdominal ultrasound (TAUS) at minipuberty., Methods: Secondary analysis from The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222). Healthy infant girls (n=302, age 3.4 months (0.4) mean (±SD): mamma tissue diameter (mm), n=300. TAUS: uterine volume (n=230), endometrial thickness (n=255), ovarian volume, antral follicle count (total/2-4mm/≥5mm) (n=203).Blood samples (n=269/302=89%): AMH, FSH, LH, inhibin B (immunoassays), progesterone (PROG), androstenedione (Adione), testosterone (T), estrone (E1), estradiol (E2) (LC/MS-MS).Statistics: Pearson/Spearman´s correlation coefficient (parametric/non-parametric data)., Results: Total follicle count correlated positively with ovarian volume (r= 0.606, p<0.001), AMH (r=0.378, p<0.001), inhibin B (r=0.251, p<0.001), and negatively with FSH concentrations (r=-0.327, p<0.001). Larger follicles (≥5mm) correlated positively with AMH (r=0.264, p<0.001), inhibin B (0.230, p=0.002), E1 (r=0.209, p=0.004), E2 (r=0.269, p<0.001), PROG (r=0.160, p=0.031) and T (r=0.210, p=0.004) and negatively with FSH (r=-0.183, p=0.015). Circulating E1 and E2 levels correlated with the size of estrogen-responsive tissue sizes: E2 vs. uterine volume (r=0.134, p=0.054), E2 vs. endometrial thickness (r=0.155, p=0.020), E1 and E2 vs. mammary tissue diameter (r=0.213 and r=0.198, respectively, both p < 0.001)., Conclusions: Correlations between reproductive hormones and the number of antral follicles suggest that negative feedback in the female HPG axis is established during minipuberty, with ovarian activity promoting uterine and glandular breast tissue growth We provide normative data of infant ovarian- and uterine morphology directly implementable to a clinical setting., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Introduction: Obstetrics research has predominantly focused on the management and identification of factors associated with labor dystocia. Despite these efforts, clinicians currently lack the necessary tools to effectively predict a woman's risk of experiencing labor dystocia. Therefore, the objective of this study was to create a predictive model for labor dystocia., Material and Methods: The study population included nulliparous women with a single baby in the cephalic presentation in spontaneous labor at term. With a cohort-based registry design utilizing data from the Copenhagen Pregnancy Cohort and the Danish Medical Birth Registry, we included women who had given birth from 2014 to 2020 at Copenhagen University Hospital-Rigshospitalet, Denmark. Logistic regression analysis, augmented by a super learner algorithm, was employed to construct the prediction model with candidate predictors pre-selected based on clinical reasoning and existing evidence. These predictors included maternal age, pre-pregnancy body mass index, height, gestational age, physical activity, self-reported medical condition, WHO-5 score, and fertility treatment. Model performance was evaluated using the area under the receiver operating characteristics curve (AUC) for discriminative capacity and Brier score for model calibration., Results: A total of 12,445 women involving 5,525 events of labor dystocia (44%) were included. All candidate predictors were retained in the final model, which demonstrated discriminative ability with an AUC of 62.3% (95% CI:60.7-64.0) and Brier score of 0.24., Conclusions: Our model represents an initial advancement in the prediction of labor dystocia utilizing readily available information obtainable upon admission in active labor. As a next step further model development and external testing across other populations is warranted. With time a well-performing model may be a step towards facilitating risk stratification and the development of a user-friendly online tool for clinicians., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nathan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Problem/background: Immersion in water has known benefits, such as reducing pain and shortening the duration of labour. The relationship between waterbirth and perineal injury remains unclear., Aim: To compare the incidence of perineal injury in waterbirth and birth on land among low-risk women. Secondary outcomes were postpartum haemorrhage and 5-minute Apgar scores <7., Methods: Prospective cohort study of 2875 low-risk women who planned a home birth in Denmark, Iceland, Norway, and Sweden in 2008-2013 and had a spontaneous vaginal birth without intervention. Descriptive statistics and logistic regression were performed., Findings: A total of 942 women had a waterbirth, and 1933 gave birth on land. The groups differed in their various background variables. Multiparous women had moderately lower rates of intact perineum (59.3% vs. 63.9%) and primiparous women had lower rates of episiotomies (1.1% vs. 4.8%) in waterbirth than in birth on land. No statistically significant differences were detected in adjusted regression analysis on intact perineum in waterbirth (primiparous women's aOR = 1.03, CI 0.68-1.58; multiparous women's aOR = 0.84, CI 0.67-1.05). The rates of sphincter injuries (0.9% vs. 0.6%) were low in both groups. No significant differences were detected in secondary outcomes., Discussion: The decreased incidence of intact perineum among multiparous women was modest and inconclusive, and the prevalence of sphincter injury was low., Conclusion: Low-risk women contemplating waterbirth should be advised to weigh the risks and benefits detected in this study against previously established benefits of waterbirth and should make an informed choice based on their values., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The dynamic capacity of the hypothalamic-pituitary-adrenal (HPA) axis supports healthy adaptions to stress and play a key role in maintaining mental health. Perinatal adaptations in the HPA-axis dynamics in terms of the Cortisol Awakening Response (CAR), may be involved in dysregulation of perinatal mental health. We aimed to determine if CAR and absolute evening cortisol early postpartum differed from non-perinatal women and evaluate the association between the CAR and maternal mental well-being., Methods: The CAR was computed as the area under the curve with respect to increase from baseline from serial home-sampling of saliva across 0-60 minutes from awakening. We evaluated differences in CAR and absolute evening cortisol between postpartum women (N=50, mean postpartum days: 38, SD: ±11) and non-perinatal women (N=91) in a multiple linear regression model. We also evaluated the association between CAR and maternal mental well-being in a multiple linear regression model., Results: We found that healthy postpartum women had a blunted CAR (p<0.001) corresponding to 84% reduction and 80% lower absolute evening cortisol (p<0.001) relative to non-perinatal healthy women. In the postpartum group, there was a trend-level association between lower CAR and higher scores on the WHO Well-Being Index (WHO-5) (p=0.048) and lower Edinburgh Postnatal Depression Scale (EPDS) scores (p=0.04)., Conclusion: Our data emphasize the unique hormonal landscape during the postpartum period in terms of blunted CAR and lower absolute evening cortisol in healthy women early postpartum compared to non-perinatal. Our findings show a potential association between a reduced CAR and improved mental well-being during early motherhood, which suggests that reduced CAR might reflect healthy adjustment to early motherhood., Competing Interests: Declaration of Competing Interest VGF discloses that she has received honoraria in the form of consulting fees from SAGE Therapeutics, Lundbeck Pharma A/S, Janssen Cilag A/S, and Gedeon-Richter A/S. All other authors have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Violence against women (VAW) is a global challenge also in the childbearing period. Despite high gender equality, there is a high prevalence of VAW in the Nordic countries. This scoping review aims to explore predictors for and consequences of a history of violence on women's pregnancy and childbirth in the Nordic countries, including women's experience of the impact of violence and the interventions used to detect, address consequences, and prevent further violence. The framework by Arksey and O'Malley was followed, and English, Finnish, Icelandic, Norwegian, Danish, and Swedish literature was included. The population was women aged ≥18 residing in the Nordic countries during the perinatal period. Eight databases were searched: MEDLINE, CINAHL, PubMed, PsycINFO, Web of Science, ASSIA, Social Services-, and Sociological abstracts. There was no limitation of the search time frame. The initial screening resulted in 1,104 records, and after removing duplicates, 452 remained. Finally, 61 papers met the inclusion criteria. The results covering the past 32 years indicated that childbearing women with a history of violence are at greater risk of common complaints and hospitalization during pregnancy, fear of childbirth, Cesarean section, breastfeeding difficulties, and physical and mental health problems. While extensive research was found on the associations between a history of and current violence and outcomes related to pregnancy, there was a lack of intervention studies and studies from Finland. Efforts must be made to scientifically test the methods used to reduce and treat the adverse effects of a history of violence and prevent further violence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: The anogenital distance (AGD) is considered a postnatal readout of early fetal androgen action. Little is known of prenatal AGD and how it correlates with AGD postnatally., Objectives: We present longitudinal measurements of fetal- and infant AGD. We evaluate the impact of testosterone and dihydrotestosterone at minipuberty on AGD and penile size., Design: Secondary analyses of an observational, prospective pregnancy and birth cohort, COPANA (2020-2022)., Setting: Copenhagen University Hospital - Rigshospitalet., Participants: 685 healthy, singleton pregnant women enrolled, 657 women attended 3rd trimester ultrasound, 589 infants completed follow-up., Main Outcome Measures: 3rd trimester ultrasound (GW29-34): Fetal AGD. Minipuberty clinical examination (app. 3.5 months postpartum): infant AGD, penile width and stretched length (SPL), circulating testosterone and dihydrotestosterone (LC-MS/MS)., Results: AGD was available in 650/657 fetuses (310 boys) and 588/589 infants (287 boys). Boys had longer fetal and infant AGD compared to girls; fetal AGDas: mean (SD) 21.4 mm (±3.5), fetal AGDaf: 12.8 mm (±2.3), p < 0.001, infant AGDas: 32.0 mm (±5.6) and infant AGDaf: 15.8 (±3.3), p < 0.001. Fetal AGD correlated with infant AGD in boys and girls (Spearman's r = 0.275, p < 0.001 and r = 0.189, p = 0.001 respectively), but not with circulating testosterone or dihydrotestosterone at minipuberty. Penile size correlated positively with circulating androgen levels at minipuberty, i.e.: SPL vs testosterone: r = 0.235, p < 0.001., Conclusions: AGD is sexual dimorphic already in the 3rd trimester. Fetal and infant AGD correlates. AGD is associated with body size but not circulating androgen levels at minipuberty. These findings suggest that fetal and infant AGD, reflect androgen action during early fetal development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Development of the gonads during fetal life is complex and vital for adult reproductive health. Cell and animal studies have shown an alarming effect of mild analgesics on germ cells in both males and females. More than 50% of pregnant women use mild analgesics during pregnancy, which potentially could compromise the reproductive health of the next generation., Objectives: We present a research protocol designed to evaluate the effect of prenatal exposure to mild analgesics and endocrine-disrupting chemicals on gonadal function in the offspring., Population: Healthy, singleton pregnant women and their partners., Design: The COPANA cohort is a prospective, observational pregnancy and birth cohort., Methods: Participants were enrolled during the first trimester of pregnancy. Information on the use of mild analgesics was collected retrospectively 3 months prior to pregnancy and prospectively every 2 weeks throughout the study. We collected extensive data on lifestyle and reproductive health. Biospecimens were collected in the first trimester (maternal and paternal urine- and blood samples), in the third trimester in conjunction with a study-specific ultrasound scan (maternal urine sample), and approximately 3 months post-partum during the infant minipuberty period (maternal and infant urine- and blood samples). A comprehensive evaluation of reproductive function in the infants during the minipuberty phase was performed, including an ultrasound scan of the testis or ovaries and uterus., Preliminary Results: In total, 685 pregnant women and their partners were included between March 2020 and January 2022. A total of 589 infants (287 males) and their parents completed the follow-up during the minipuberty phase (December 2020-November 2022)., Conclusions: The Copenhagen Analgesic Study holds the potential to provide novel and comprehensive insights into the impact of early and late prenatal exposure to mild analgesics and other endocrine-disrupting chemicals on future reproductive function in the offspring., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Aims: Paracetamol is commonly consumed by pregnant women, even though recent data have questioned its safety. Having chronic medical diseases (CMDs) may influence the prevalence of use during pregnancy. We aimed to assess the prevalence and patterns of use 3 months prior to pregnancy and in the first trimester among women with and without CMDs and the potential influence of CMDs on frequent use in the first trimester., Methods: We used patient-reported data from the Copenhagen Pregnancy Cohort from 1 October 2013 to 23 May 2019 with information on CMDs and paracetamol use. Prevalence and patterns of use were assessed descriptively and by multivariable logistic regression models., Results: We included 24 019 pregnancies. Use of paracetamol prior to and in early pregnancy was significantly higher among women with CMDs compared to women without (40.7% vs. 35.8% and 9.1% vs. 5.1%, respectively). Women with CMDs were 2.7 times more likely to have a frequent intake compared to women without [aOR 2.69 (95% CI 2.05-3.32)]. Migraine, rheumatoid arthritis and mental disease were associated with a higher use of paracetamol [aOR 4.39 (3.20-6.02), aOR 4.32 (2.41-7.72) and aOR 2.74 (1.67-4.49), respectively]., Conclusions: Women with CMDs had a higher paracetamol use before and during pregnancy than women without CMDs. Women with migraine, rheumatoid arthritis and mental disease showed the highest risk of frequent use. This study highlights the importance of discussing pain relief in pregnancy and evaluating the influence of maternal CMDs when assessing adverse effects of paracetamol use during pregnancy., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To identify maternal factors associated with labor dystocia in low-risk nulliparous women., Methods: MEDLINE, Embase, ClinicalTrials.gov, Cochrane, and CINAHL were searched for intervention studies and observational studies published from January 2000 to January 2022. Low-risk was defined as nulliparous women with a singleton, cephalic birth in spontaneous labor at term. Labor dystocia was defined by national or international criteria or treatment. Countries were restricted to OECD members. Two authors independently screened 11,374 titles and abstracts, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale. Results were presented narratively and by meta-analysis when compatible., Results: Seven cohort studies were included. Overall, the certainty of the evidence was moderate. Three studies found that higher maternal age was associated with an increased frequency of labor dystocia (relative risk 1.68; 95% CI 1.43-1.98). Further three studies found that higher maternal BMI was associated with increased frequency of labor dystocia (relative risk 1.20; 95% CI 1.01-1.43). Maternal short stature, fear of childbirth, and high caffeine intake were also associated with an increased frequency of labor dystocia, while maternal physical activity was associated with a decreased frequency., Conclusion: Maternal factors associated with an increased frequency of labor dystocia were mainly maternal age, physical characteristics, and fear of childbirth. Maternal physical activity was associated with a decreased frequency. Intervention studies targeting these maternal factors would need to be initiated before or early in pregnancy to test the causality of the identified factors and labor dystocia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To explore attitudes to and experiences using a smartphone-based self-test for prediction of pre-eclampsia among pregnant women., Design: A qualitative, descriptive study., Setting: An obstetrical care unit at a university hospital in Denmark., Participants: Twenty women who had participated in the Salurate trial, a clinical trial testing the efficacy of a smartphone-based self-test for prediction of pre-eclampsia, were purposefully chosen for the study, using maximum variation sampling., Data Collection and Analysis: Data were collected by semistructured, individual, face-to-face interviews conducted from 4 October 2018 to 8 November 2018. Data were transcribed verbatim and analysed by means of thematic analysis., Results: Qualitative thematic analysis resulted in the identification of three main themes: Raising awareness, self-testing has the potential to be an integrated part of pregnancy and trusting in technology. Two subthemes were identified under each main theme., Conclusions: The smartphone-based self-test for prediction of pre-eclampsia has potential to be integrated into antenatal care, and women found it feasible to use. However, testing affected the participating women psychologically, leading to feelings of worry as well as safety. Therefore, if self-testing is implemented, it is important to take actions to handle adverse psychological side effects, including increasing knowledge on pre-eclampsia and having healthcare professionals ongoingly address the psychological state of women throughout pregnancy. In addition, it is essential to emphasise the importance of subjective bodily sensations during pregnancy, including fetal movements. Further studies on the experience of being labelled low risk versus high risk for pre-eclampsia are warranted since this was not investigated in this trial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Threatened preterm delivery is a serious obstetrical complication and has for decades been prescribed physical activity restrictions (AR). Adherence to the recommended level of physical AR is however unknown. This study aimed to assess the objectively measured different physical positions and activities of pregnant women recommended AR due to threatened preterm delivery complications, compared to a reference group of uncomplicated pregnant women without restrictions, and to explore if admission status influenced adherence to AR., Methods: A Danish descriptive, clinical multi-center study included singleton pregnancies between 22-33 gestational weeks admitted to an antenatal ward or during midwife consultations either prescribed AR due to threatened preterm delivery or uncomplicated controls without restrictions. For seven days participants wore two tri-axial accelerometric SENS® monitors. Accelerometric data included time spent in five different positions, activities, and step counts. At inclusion demographic and obstetric information was collected., Results: Seventy-two pregnant women participated; 31% were prescribed strict AR, 15% moderate, 3% light, 8% unspecified, and 43% had no AR. Strict AR participants rested in the supine/lateral position for 17.7 median hours/day (range:9.6-24.0); sat upright 4.9 h/day (0.11-11.7); took 1,520steps/day (20-5,482), and 64% were inpatients. Moderate AR participants rested in the supine/lateral position for 15.1 h/day (11.5-21.6); sat upright 5.6 h/day (2.0-9.3); took 3,310steps/day (467-6,968), and 64% were outpatients. Participants with no AR rested 10.5 h/day (6.3-15.4) in supine/lateral position; sat upright 7.6 h/day (0.1-11.4) and took 9,235steps/day (3,225-20,818). Compared to no restrictions, participants with strict or moderate AR spent significant more time in physical resting positions and took significant fewer mean steps. Among strict AR admission status did not alter time spent in the physical positions, nor the step count., Conclusions: Overall, participants adhered highly to the recommended AR. However, discriminating between strict and moderate AR recommendations did not alter how physical resting positions and activities were carried out. The admission status did not influence how participants adhered to strict AR., (© 2023. The Author(s).)

Introduction: Preeclampsia is associated with adverse maternal and neonatal outcomes. It is unclear whether multivitamin use reduces the risk of preeclampsia. This systematic review and meta-analysis aimed to evaluate the association between multivitamin use and the risk of preeclampsia., Material and Methods: We searched PubMed, Embase and the Cochrane Library from database inception to July 2021. Randomized controlled trials (RCTs), case-control and cohort studies assessing the association between multivitamin use and risk of preeclampsia were eligible. Studies of treatment with a single micronutrient were excluded. Relative risks and 95% confidence intervals (95% CI) were calculated using random-effects models. RoB2, the Newcastle Ottawa Scale and GRADE were used to assess risk of bias and quality of evidence. The protocol was registered in PROSPERO (no. CRD42021214153)., Results: Six studies were included (33 356 women). Only two RCTs were found, both showing a significantly decreased risk of preeclampsia in multivitamin users. These studies were not compatible for meta-analysis due to clinical heterogeneity. A meta-analysis of observational studies using a random-effects model showed an unchanged risk of preeclampsia following multivitamin use (relative risk 0.85, 95% CI 0.69-1.03). The quality of evidence according to GRADE was very low., Conclusions: Very weak evidence suggests that multivitamin use might reduce the risk of preeclampsia; however, more research is needed. Large RCTs should be prioritized. The results of this review do not allow any final conclusions to be drawn regarding a preventive effect of multivitamin use in relation to preeclampsia., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Poor sleep quality is common during pregnancy. Our objective was to evaluate the effect of supervised group physical exercise on self-reported sleep quality in pregnant women with or at high risk of depression, and secondly, to describe the association between sleep quality and psychological well-being during pregnancy and postpartum. This was a secondary analysis of a randomized controlled trial (n = 282) (NCT02833519) at Rigshospitalet, Denmark. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), psychological well-being by the five-item WHO Well-Being Index (WHO-5). The intention-to-treat analysis showed no difference in mean global PSQI score neither at 29−34 weeks, 6.56 (95% CI: 6.05−7.07) in the intervention group and 7.00 (95% CI: 6.47−7.53) in the control group, p = 0.2, nor at eight weeks postpartum. Women with WHO-5 ≤ 50 reported higher mean global PSQI scores at baseline, 7.82 (95% CI: 7.26−8.38), than women with WHO-5 score > 50, mean 5.42 (95% CI: 5.02−5.82), p < 0.0001. A significant difference was also present post-intervention and eight weeks postpartum. No significant effect of group exercise regarding self-reported sleep quality was seen at 29−34 weeks of gestation or postpartum. Low psychological well-being was associated with poor sleep quality during pregnancy and postpartum.

In 2013, the Danish Health Authorities recommended a change in prophylactic iron supplementation to 40-50 mg/d from gestational week 10. Hence, the aims of the present study were (1) to estimate the prevalence of women who follow the Danish recommendation on iron supplementation during the last 3 weeks of the first trimester of pregnancy and (2) to identify potential sociodemographic, reproductive and health-related pre-pregnancy predictors for iron supplementation during the first trimester. We conducted a cross-sectional study with data from the hospital-based Copenhagen Pregnancy Cohort. Characteristics were analysed by descriptive statistics and multivariable logistic regression analysis was performed to examine the associations between predictors and iron supplementation during the last 3 weeks of the first trimester. The study population consisted of 23 533 pregnant women attending antenatal care at Copenhagen University Hospital - Rigshospitalet from October 2013 to May 2019. The prevalence of iron supplementation according to recommendations was 49⋅1 %. The pre-pregnancy factors of ≥40 years of age, the educational level below a higher degree and a vegetarian or vegan diet were identified as predictors for iron supplementation during the first trimester of pregnancy. Approximately half of the women were supplemented with the recommended dose of iron during the first trimester of pregnancy. We identified pre-pregnancy predictors associated with iron supplementation. Interventions that target women of reproductive age are needed. An enhanced focus on iron supplementation during pregnancy should be incorporated in pre-pregnancy and interpregnancy counselling., (© The Author(s) 2022.)

Introduction: A pandemic may negatively influence psychological well-being in the individual. We aimed to assess the potential influence of the first national lockdown in Denmark (March to June 2020) due to the COVID-19 pandemic on psychological well-being and the content and degree of worries among pregnant women in early pregnancy., Material and Methods: In this hospital-based cross-sectional study based on self-reported data we compared psychological well-being and worries among women who were pregnant during the first phase of the pandemic (COVID-19 group) (n = 685), with women who were pregnant the year before (Historical group) (n = 787). Psychological well-being was measured by the five-item World Health Organization Well-being Index (WHO-5), using a score ≤50 as indicator of reduced psychological well-being. Differences in WHO-5 mean scores and in the prevalence of women with score ≤50 were assessed using general linear and log-binomial regression analyses. The Cambridge Worry Scale was used to measure the content and degree of major worries. To detect differences between groups, Pearson's Chi-square test was used., Results: We found no differences in mean WHO-5 score between groups (mean difference) 0.1 (95% CI -1.5 to 1.6) or in the prevalence of women with WHO-5 score ≤50 (prevalence ratio 1.04, 95% CI 0.83-1.29) in adjusted analyses. A larger proportion of women in the COVID-19 group reported major worries about Relationship with husband/partner compared with the Historical group (3% [n = 19] vs 1% [n = 6], p = 0.04), and 9.2% in the COVID-19 group worried about the possible negative influence of the COVID-19 restrictions., Conclusions: Our findings indicate that national restrictions due to the COVID-19 pandemic did not influence the psychological well-being or the content and degree of major worries among pregnant women. However, a larger proportion of women in the COVID-19 group reported major worries concerning Relationship with husband/partner compared with the Historical group and 9.2% in the COVID-19 group worried about the possible negative influence of the COVID-19 restrictions., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To explore maternity care experiences and needs of women with various types of chronic medical conditions receiving specialised maternity care. Design A qualitative descriptive study., Setting: A highly specialised hospital providing maternity care to women with high-risk pregnancies in Copenhagen, Denmark. Participants Fourteen purposefully selected women referred to specialist maternity care at a large tertiary hospital due to one or more chronic medical conditions., Methods: Individual in-depth interviews (n = 14) were performed between January 2018 and June 2019. Analysed using thematic analysis., Results: One overarching theme was identified: Monitored but not sufficiently guided. Three main themes unfolding this overarching theme were: Chronic condition as determining pregnancy care, Childbearing woman as messenger and interpreter, and Feelings of abandonment after giving birth., Key Conclusions: Across various types of chronic medical conditions, women expressed a need for increased continuity in specialised maternity care. Healthcare professionals should help women with chronic medical conditions navigate the healthcare system and interpret complex information., Implications for Practice: Pregnancy should be recognised as a significant life event, even though the childbearing woman is living with a chronic medical condition, and professionals should emphasise the aspects of pregnancy that develop uncomplicated. Information about the anticipated development of chronic medical conditions postpartum and concerns regarding breastfeeding could preferably be addressed during pregnancy. Continuity of care was particularly important to the women and could relieve some of the worrying women experienced during pregnancy., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Postpartum depression affects 10%-15% of women and has a recurrence rate of 40% in subsequent pregnancies. Women who develop postpartum depression are suspected to be more sensitive to the rapid and large fluctuations in sex steroid hormones, particularly estradiol, during pregnancy and postpartum. This trial aims to evaluate the preventive effect of 3 weeks transdermal estradiol treatment immediately postpartum on depressive episodes in women at high risk for developing postpartum depression., Methods and Analysis: The Maternal Mental Health Trial is a double-blind, randomised and placebo-controlled clinical trial. The trial involves three departments of obstetrics organised under Copenhagen University Hospital in Denmark. Women who are singleton pregnant with a history of perinatal depression are eligible to participate. Participants will be randomised to receive either transdermal estradiol patches (200 µg/day) or placebo patches for 3 weeks immediately postpartum. The primary outcome is clinical depression, according to the Diagnostic and Statistical Manual of Mental Disorders-V criteria of Major Depressive Disorder with onset at any time between 0 and 6 months postpartum. Secondary outcomes include, but are not limited to, symptoms of depression postpartum, exclusive breastfeeding, cortisol dynamics, maternal distress sensitivity and cognitive function. The primary statistical analysis will be performed based on the intention-to-treat principle. With the inclusion of 220 participants and a 20% expected dropout rate, we anticipate 80% power to detect a 50% reduction in postpartum depressive episodes while controlling the type 1 error at 5%., Ethics and Dissemination: The study protocol is approved by the Regional Committees on Health Research Ethics in the Capital Region of Denmark, the Danish Medicines Agency and the Centre for Data Protection Compliance in the Capital Region of Denmark. We will present results at scientific meetings and in peer-reviewed journals and in other formats to engage policymakers and the public., Trial Registration Number: NCT04685148., Competing Interests: Competing interests: VGF declares that she has received honorarium as a consultant for SAGE therapeutics and Lundbeck Pharma A/S., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Pregnancy is a time of uncertainty and worries are common. Pregnant women with somatic chronic medical conditions (SCMC) are at higher risk of adverse pregnancy outcomes and perinatal mental illness than women without SCMC. We aimed to describe the degree and content of worries in early pregnancy among Danish women with SCMC compared with women without SCMC., Study Design: We conducted a cross-sectional study with self-reported questionnaires answered by 28,794 women from 2012─2019 during 1st trimester at a large university hospital in Denmark., Main Outcome Measures: We used the Cambridge Worry Scale (CWS). The outcomes of interest were the prevalence of major worry at item level (n/%) and the total CWS score (mean/SEM) as expression of the degree and content of worries. Univariate and multivariable regression analysis were performed., Results: Women with SCMC reported a significantly higher total CWS score (aMD 1.50, 95% CI: 1.20-1.80). Women with SCMC were significantly more likely to report major worry in relation to own health (aOR 2.72, 95% CI: 2.43-3.08), the baby's health (aOR 1.40 95% CI 1.31-1.52), the process of giving birth (aOR 1.12, 95% CI: 1.04-1.21), the possibility of preterm labor (aOR 1.44, 95% CI: 1.28-1.63), and miscarriage (aOR 1.34, 95% CI: 1.24-1.43)., Conclusion: Women with SCMC reported higher overall degree of worry during early pregnancy and an increased risk of major worry in relation to own health, pregnancy complications and giving birth. In antenatal care, these worries should be addressed by clinicians., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The hypothalamic-pituitary-gonadal (HPG) axis governs sexual maturation and reproductive function in humans. In early postnatal life, it is transiently active during which circulating sex steroids reach adult levels. While this so-called minipuberty represents a universal phenomenon in infants of both sexes, its role for early maturation and growth remains incompletely understood., Objectives: To provide normative data on auxology as well as serum and urinary hormone levels in healthy, full-term infants throughout the first year of life and to investigate associations of postnatal HPG axis dynamics as well as hormonal, genetic and environmental exposures with early genital development and growth., Population: Healthy, Danish, full-term, singleton newborns including their parents., Design: Single-centre, prospective, observational longitudinal pregnancy and birth cohort., Methods: Newborns were followed with six repeated clinical examinations during a one-year follow-up period. An umbilical cord blood sample was drawn at birth. At each visit, infants underwent a clinical examination focusing on auxology and genital development. Further, blood (serum, plasma, DNA) and urine samples were collected at each visit. Mothers and fathers underwent a clinical examination and provided blood samples prior to and after birth. A subset of parents provided urine samples and breast milk samples. Pregnancy and obstetrical outcomes, and detailed parental questionnaires were compiled., Preliminary Results: Between August 2016 and August 2018, 2481 women with singleton pregnancies were invited to participate of which 298, including their partners, were enrolled (12.0%). A total of 268 healthy, full-term newborns born appropriate for gestational age (AGA) were included at birth, 233 newborns participated in the postnatal follow-up period and 186 completed the one-year follow-up period (9.4% and 7.5%, respectively)., Conclusion: The COPENHAGEN Minipuberty Study provides detailed, longitudinal data on early genital development and growth including hormonal and genetic profiles and environmental exposure in healthy infants including additional data in their parents., (© 2021 John Wiley & Sons Ltd.)

The proportion of childbearing women with pre-existing chronic medical conditions (CMC) is rising. In a randomized controlled trial, we aimed to evaluate the effects of a midwife-coordinated maternity care intervention (ChroPreg) in pregnant women with CMC. The intervention consisted of three main components: (1) Midwife-coordinated and individualized care, (2) Additional ante-and postpartum consultations, and (3) Specialized known midwives. The primary outcome was the total length of hospital stay (LOS). Secondary outcomes were patient-reported outcomes measuring psychological well-being and satisfaction with maternity care, health utilization, and maternal and infant outcomes. A total of 362 women were randomized to the ChroPreg intervention ( n = 131) or Standard Care ( n = 131). No differences in LOS were found between groups (median 3.0 days, ChroPreg group 0.1% lower LOS, 95% CI -7.8 to 7%, p = 0.97). Women in the ChroPreg group reported being more satisfied with maternity care measured by the Pregnancy and Childbirth Questionnaire (PCQ) compared with the Standard Care group (mean PCQ 104.5 vs. 98.2, mean difference 6.3, 95% CI 3.0-10.0, p < 0.0001). In conclusion, the ChroPreg intervention did not reduce LOS. However, women in the ChroPreg group were more satisfied with maternity care.

The first national lockdown in Denmark due to the COVID-19 pandemic was declared on 11 March 2020. From this date, national restrictions were imposed. We aimed to assess the potential influence of this first nationwide lockdown on exercise, alcohol consumption, and smoking in early pregnancy. Using a cross-sectional study based on routinely collected patient-reported data, we compared the lifestyle habits of women who were pregnant during the first phase of the pandemic (COVID-19 group) ( n = 685) with those of women who were pregnant the year before (Historical group) ( n = 787). We found a reduction in any exercise (PR = 0.91, 95% CI (0.84 to 0.99), in adherence to national recommendations of exercise (PR = 0.89, 95% CI (0.80 to 0.99), in cycling (15% vs. 28%, p < 0.0001), and swimming (0.3% vs. 3%, p = 0.0002) in the COVID-19 group compared with the Historical group. The prevalence of binge drinking was reduced in the COVID-19 group compared with the Historical group (PR = 0.80, 95% CI (0.68 to 0.93). In contrast, the prevalence of any weekly alcohol consumption and smoking cessation during pregnancy was similar between groups. Our findings indicate that national restrictions due to the COVID-19 pandemic influenced the lifestyle habits of pregnant women and should be addressed in antenatal counseling.

Introduction: Pregnancy planning allows women to engage in pregnancy planning behaviors to optimize health status in the preconception period. Women with chronic medical conditions have a higher risk for adverse pregnancy outcomes and therefore preconception care is recommended. The aim was to compare pregnancy planning among women with and without chronic medical conditions, and to assess adherence to the recommended pregnancy planning behaviors on folic acid intake, physical activity and abstention from smoking and alcohol, among women with and without chronic medical conditions stratified by pregnancy planning., Material and Methods: A cross-sectional study with data from 28 794 pregnancies. Pregnancy planning was measured with the Swedish Pregnancy Planning Scale. Multiple Poisson regression with robust variance estimates was used to assess the associations between chronic medical condition (yes/no and main categories) and pregnancy planning, and chronic medical condition status and pregnancy planning behaviors stratified by pregnancy planning., Results: In the study population, 74% reported high degree of pregnancy planning, and 22% had one or more chronic medical conditions. We found no overall association between chronic medical condition and pregnancy planning (adjusted rate ratio [RR] 1.00, 95% confidence interval [CI] 0.98-1.01). However, women with type 2 diabetes and mental illness were significantly less likely to plan their pregnancies than women without these conditions (aRR 0.73, 95% CI 0.61-0.88; aRR 0.91, 95% CI 0.87-0.96, respectively). Women with chronic medical conditions were more likely to adhere to the recommended planning behaviors; intake of folic acid, abstention from alcohol prior to pregnancy and no binge drinking in early pregnancy., Conclusions: Overall, pregnancies were highly planned. Women with chronic medical conditions did not show a higher degree of pregnancy planning than women without chronic medical conditions but were, however. more likely to adhere to the generally recommended pregnancy planning behaviors (ie intake of folic acid and abstention from alcohol intake). Only women with mental illness and type 2 diabetes reported a lower degree of pregnancy planning. It is important that we continuously address pregnancy planning and planning behaviors for both women with and women without chronic medical conditions, especially women with type 2 diabetes and mental illness., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Introduction: Depression is expected to be the leading cause of disability worldwide by 2030. The prevalence is increasing and is two-fold higher in women than in men, women being at particularly high risk during hormonal transition phases such as pregnancy and the postpartum period. The objective for this trial was to assess the effect of supervised group exercise on psychological well-being and symptoms of depression among pregnant women with or at high risk of depression., Material and Methods: This study was undertaken at the Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark, from August 2016 to September 2018. Pregnant women with a current or previous history of depression and/or anxiety requiring treatment within the last 10 years, or use of antidepressants 3 months before or during pregnancy, were randomly assigned to 12 weeks of supervised group exercise from 17 to 22 weeks of gestation twice weekly, or to a control group. The primary outcome was self-reported psychological well-being at 29-34 weeks of gestation, measured by the five-item World Health Organization Well-being Index (WHO-5). Secondary outcomes included delivery outcomes and psychological well-being (WHO-5) 8 weeks postpartum., Results: The intention-to-treat analysis showed no significant effect on psychological well-being on the primary outcome. Mean WHO-5 score in the intervention group was 2.0 (95% CI -1.3 to 5.2, P = .2) higher than in the control group. Per protocol analysis of women who attended ≥75% of the exercise sessions showed a statistically significant higher mean WHO-5 score relative to the control group at gestational weeks 29-34. Eight weeks postpartum the intervention group reported higher psychological well-being than the control group, mean difference in WHO-5 score of 5.5 (95% CI 1.0-10.1, P = .04)., Conclusions: Supervised group exercise did not improve psychological well-being for women with or at high risk of depression at 29-34 weeks of gestation. Eight weeks postpartum the intervention group reported significantly higher psychological well-being than the control group. Based on our results, supervised exercise in groups is a safe complementary course of treatment alongside the existing antenatal care., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Children born preterm have an increased risk of severe morbidity, e.g. cerebral palsy (CP), compared to children born at term. CP cannot be treated, which is why a prophylactic approach is essential, as argued in this review. Six randomised controlled trials (RCTs) have provided data on MgSO4 treatment as CP neuroprotection in preterm birth, including a new RCT from Denmark. Recently, an updated meta-analysis with trial sequential analysis detected a significant neuroprotective effect of MgSO4 treatment in preterm birth. There is now sufficient evidence, that MgSO4 treatment should be used as neuroprotection in preterm birth.

Introduction: The aim of this study was to assess the association between multivitamin intake during pregnancy and the risk of preterm birth and very preterm birth., Methods: The study population comprised 15,629 women from the Copenhagen Pregnancy Cohort with data on pregnancy multivitamin intake during their first trimester who gave birth to singletons from October 2012 to October 2016. Data on pregnancy multivitamin intake were linked to the Medical Birth Registry to identify the birth outcome. The main outcome measures were preterm birth before 37 weeks of gestation and very preterm birth before 32 weeks of gestation., Results: Among the included women, 85.6% had taken daily pregnancy multivitamins during their first trimester. We found no evidence that pregnancy multivitamin intake during the first trimester was associated with a decreased risk of preterm birth (adjusted odds ratio (OR) = 1.01; 95% confidence interval (CI): 0.77-1.33) or very preterm birth (adjusted OR = 1.06; 95% CI: 0.63-1.77). Stratification for BMI into lesser-than 25 kg/m2 and ≥ 25 kg/m2 did not alter these findings., Conclusions: Pregnancy multivitamin intake during the first trimester was not associated with a decreased risk of preterm birth or very preterm birth among women in a high-income population., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Ordinary meta-analyses indicate that magnesium sulphate (MgSO 4 ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g. by trial sequential analysis (TSA), for which there are previously insufficient samples to draw a firm conclusion. Recently, a randomised controlled trial (RCT) provided additional data that potentially increased the sample size such that a new TSA might detect a statistically significant effect., Objectives: To assess the possible fetal neuroprotective effect of MgSO 4 for women at imminent risk for preterm delivery in an updated systematic review with meta-analysis and TSA., Search Strategy: We searched MEDLINE, Embase, Cochrane and ClinicalTrials.gov on 8 October 2019. The search strategy clustered terms describing the MgSO 4 intervention and preterm delivery., Selection Criteria: RCTs., Data Collection and Analysis: Two reviewers extracted the data. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models. A TSA was applied to the primary outcome, CP. The quality of the evidence was assessed using GRADE. The protocol was registered in PROSPERO (registration: CRD42019151441)., Main Results: We identified six eligible trials (5917 women). MgSO 4 intervention in women at imminent risk for preterm birth decreased the offspring's CP risk (meta-analysis RR 0.68, 95% CI 0.54-0.85; TSA RR 0.69, 95% CI 0.48-0.97)., Conclusions: This systematic review with meta-analysis and TSA shows conclusively that MgSO 4 , when given to women at imminent risk for preterm delivery, decreases the offspring's CP risk., Tweetable Abstract: Antenatal magnesium sulphate decreases the risk of cerebral palsy in children born preterm., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Objective: To study the effect of antenatal magnesium sulphate (MgSO 4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis., Design: Double-blind, randomised, placebo-controlled, multi-centre trial., Setting: Fourteen Danish obstetric departments., Population: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children., Methods: Women were randomised to receive either a loading dose of 5 g MgSO 4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire., Main Outcome Measure: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP., Results: The crude rates of moderate to severe CP in the MgSO 4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO 4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65)., Conclusions: Antenatal MgSO 4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis., Tweetable Abstract: Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Objective: The objective of this study was to examine the association between multivitamin use in the periconceptional period and the risk of preeclampsia., Study Design: The association was investigated in a prospective cohort study. 15,154 deliveries in women followed at a large university hospital in Denmark were included between 16 September 2012 and 31 October 2016. Pregnant women were sent a questionnaire containing items related to socio-demographic-, lifestyle- and health factors. The responses on multivitamin use were merged with the preeclampsia diagnosis from the Danish Medical Birth Registry. We used multiple logistic regression analyses to assess the association and to adjust for potential confounders., Main Outcome Measures: The outcome of interest, preeclampsia, included the preeclampsia subtypes eclampsia and HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome., Results: In total 12,954 women (85%) reported multivitamin use. A diagnosis of preeclampsia was found in 397 women (2.6%). We found a similar risk of preeclampsia in multivitamin user and non-users, adjusted odds ratio (AOR) for periconceptional multivitamin use = 0.97 (95% CI: 0.70 to 1.36) and AOR for early pregnancy multivitamin use = 0.97 (95% CI: 0.71 to 1.32). Subgroup analyses stratified on body mass index showed that among women with overweight, both periconceptional and early pregnancy multivitamin use were associated with a statistically significant lower risk of preeclampsia (AOR = 0.49, 95% CI: 0.24 to 0.99 and AOR = 0.35, 95% CI: 0.18 to 0.69, respectively)., Conclusion: Periconceptional- and early pregnancy multivitamin use was found to be associated with a similar risk of preeclampsia compared to non-users., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To explore experiences with supervised group exercise during pregnancy in women with depression or low psychological well-being., Design: A qualitative descriptive study based on semi-structured, individual, in-depth interviews analyzed by means of thematic analysis., Setting: The Department of Obstetrics, Rigshospitalet, Copenhagen University Hospital, Denmark., Participants: Through a purposeful, criterion-based sampling strategy, women with a current diagnosis of depression with prescribed antidepressant and/or a score ≤50 on the five-item World Health Organization Well-being Index were included. The women were recruited from a randomized controlled trial on the effects of supervised group exercise (the EWE study) and participated in the exercise program during the period 26 January 2017-8 March 2018. A total of 282 pregnant women participated in the RCT, of which 143 women were allocated to the intervention group. Of these, 27 women were eligible and were invited; 19 accepted the invitation and were included in the current qualitative descriptive study. Diversity of age, parity, level of education and employment status was seen in the sample. The average time from completing the exercise program to conducting the interview was 6.5 months, ranging from 1 week to 13 months., Intervention: The participants were offered an in-hospital supervised group exercise program twice weekly for 12 weeks from 17-22 weeks gestation in addition to standard antenatal care., Measurements and Findings: Qualitative thematic analysis of the interviews resulted in the identification of the overarching theme: Vulnerable yet strong. This theme was comprised from three main themes (1) From judging the body to feeling it, (2) A "we" is created, and (3) Taking responsibility and succeeding, together with nine sub-themes., Key Conclusions: The supervised group exercise intervention provided experiences of peer support and increased body awareness, which contributed to an experience of improved psychological equilibrium and preparedness for the coming birth and motherhood. The findings suggest that participation in group-based supervised exercise during pregnancy in women with depression or low psychological well-being contributes to psychological resilience, which may persist as a positive influence postpartum and beyond., Implications for Practice: In-hospital supervised group-based exercise can be a safe means to health promotion in a secure environment that supports pregnant women's physical and mental well-being while also preparing them for birth and the transition to motherhood., Competing Interests: Declaration of Competing Interest None Declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to examine the feasibility of a web-based questionnaire when collecting information on alcohol consumption in pregnancy to identify women with risk drinking behaviour, and to describe factors associated with risk drinking behaviour, and the use of specialized care for prenatal risk drinking., Methods: In 2413 women referred to antenatal care at Odense University Hospital, Denmark, April-October 2018, self-reported alcohol intake was retrieved from a web-based questionnaire. Replies were screened for risk drinking behaviour: current intake of ≥7 drinks/week, ≥3 binge drinking episodes (intake of ≥5 drinks on a single occasion) in pregnancy, binge drinking after recognition of pregnancy and/or a TWEAK-score ≥ 2 points. Women with risk drinking behaviour were called to clarify the need for specialized care. A summary of the interview was obtained from the medical records., Results: Overall, 2168 (90%) completed the questionnaire. Of 2097 women providing information on alcohol intake, 77 (4%) had risk drinking behaviour. Risk drinking was associated with higher alcohol intake prior to pregnancy, spontaneous conception, younger age, nulliparity and higher level of physical activity in pregnancy. Amongst 47 women with risk drinking behaviour reached by phone, five (11%, 95% CI 4-23%) accepted examinations of the child by paediatrician and child psychologist, and <3 (not further specified due to small numbers) were referred to specialized antenatal care., Conclusions: A web-based questionnaire was feasible when collecting information on alcohol consumption in pregnancy to identify risk drinking behaviour. Women with risk drinking behaviour had a low acceptance of referral to specialized care., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Limited research has addressed whether maternal alcohol intake in early pregnancy increases the risk of spontaneous preterm birth. In the current study, we examined how alcohol binge drinking and weekly alcohol intake in early pregnancy were associated with spontaneous preterm birth in a contemporary cohort of Danish women., Methods: We included 15,776 pregnancies of 14,894 women referred to antenatal care at Copenhagen University Hospital, Denmark, between 2012 and 2016. Self-reported alcohol intake in early pregnancy was obtained from a Web-based questionnaire completed prior to the women's first visit at the department. Information on spontaneous preterm birth was extracted from the Danish Medical Birth Register. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of spontaneous preterm birth according to self-reported alcohol binge drinking and weekly intake of alcohol in early pregnancy were derived from Cox regression., Results: Women reporting 1, 2, and ≥ 3 binge drinking episodes had an aHR for spontaneous preterm birth of 0.88 (95% CI 0.68 to 1.14), 1.34 (95% CI 0.98 to 1.82), and 0.93 (95% CI 0.62 to 1.41), respectively, compared to women with no binge drinking episodes. Women who reported an intake of ≥ 1 drink per week on average had an aHR for spontaneous preterm birth of 1.09 (95% CI 0.63 to 1.89) compared to abstainers. When restricting to nulliparous women or cohabiting women with ≥ 3 years of higher education, this estimate was 1.28 (95% CI 0.69 to 2.40) and 1.20 (95% CI 0.67 to 2.15), respectively., Conclusion: We found no evidence that maternal alcohol intake in early pregnancy was associated with a higher risk of spontaneous preterm birth, neither for alcohol binge drinking nor for a low average weekly intake of alcohol., (© 2019 by the Research Society on Alcoholism.)

Background: Little is known about maternal alcohol intake in early pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in children beyond 5 years of age. We examined the association between alcohol binge drinking and weekly alcohol intake in early pregnancy and the risk of ADHD in children followed from birth to 19 years of age., Methods: We included 48,072 children born between 1998 and 2012, whose mothers participated in the Aarhus Birth Cohort. Maternal alcohol intake was obtained from a self-administered questionnaire completed in early pregnancy. ADHD diagnoses were retrieved from the Danish Psychiatric Central Research Register and the Danish National Patient Register. Crude hazard ratio and adjusted hazard ratio (aHR) of ADHD according to alcohol binge drinking or weekly intake of alcohol were calculated using the Cox regression., Results: Compared to children of women with no binge drinking episodes, we observed an aHR for ADHD of 0.91 (95% CI 0.76 to 1.08), 0.73 (95% CI 0.56 to 0.96), and 0.77 (95% CI 0.57 to 1.06) among children of women reporting 1, 2, and 3 or more binge drinking episodes, respectively. Among children of women drinking <1 drink per week, 1 drink per week, 2 drinks per week, and 3 or more drinks per week, we observed an aHR for ADHD of 0.87 (95% CI 0.74 to 1.03), 0.63 (95% CI 0.40 to 0.98), 1.30 (95% CI 0.89 to 1.92), and 0.78 (95% CI 0.38 to 1.59), respectively, when compared to children of women not drinking on a weekly basis., Conclusion: We found no evidence that binge drinking or low alcohol intake in early pregnancy was associated with the risk of ADHD in children., (© 2019 by the Research Society on Alcoholism.)

The purpose was to examine the association between exercise during pregnancy and intelligence score in offspring. We analyzed data from 4008 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, recruited during pregnancy from July 1989 to November 1991 and their sons who were registered at conscription at 17-20 years of age. The women gave information by self-administered questionnaires during the first trimester including leisure-time physical activity and weekly hours of sport. This information was linked to the sons' measures of intelligence by Børge Priens test scores from the Danish Conscription Registry. Only sons were included since very few women register at conscription in Denmark. The main outcome measure was the Børge Priens test score as a continuous variable and with a low score defined as <10% of the population score. Analyses were adjusted for maternal body mass index, years in school, and smoking. Sons of women with light and moderate to heavy leisure-time physical activity had lower risk of having a low intelligence score compared with sons of women with sedentary activity: adjusted odds ratio (aOR) 0.66 (95% CI 0.49;0.88) and 0.46 (95% CI 0.23;0.93), respectively. Furthermore, sons of women engaged in sports had lower risk of a low intelligence score: aOR 0.50 (95% CI 0.30; 0.83) for 1-2 h/wk and 0.62 (95% CI 0.35; 1.10) for ≥3 h/wk compared with no weekly sports activity. In conclusion, a higher level of physical activity during pregnancy was associated with a lower risk of low intelligence score in early adulthood in sons., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Low back pain is a common condition among childbearing women, causing physical disability and an increased risk of sick leave and obstetric complications., Aims: To assess the prevalence and intensity of low back pain during pregnancy, to describe the physical disability and sick leave in relation to the severity of low back pain and to identify predictors of moderate to severe low back pain in socio-demographic, health and obstetric characteristics among childbearing women., Methods: A cohort study was undertaken (n=566) during August 2015 to March 2016. Questionnaires were used to obtain information about low back pain intensity, physical disability due to low back pain and sick leave at 20 and 32weeks of gestation. Of the 654 eligible women, 87% completed the first questionnaire., Findings: Three out of four reported any low back pain at 20weeks of gestation, and nine out of ten women at 32weeks. Of these women, one in three reported moderate to severe pain at 20weeks, increasing to half of the women at 32weeks. Both sick leave and physical disability increased with increasing low back pain scores. Pre-pregnancy low back pain, multiparity and lower level of education were all identified as predictors of moderate to severe low back pain., Conclusions: Women with pre-pregnancy low back pain, multiparity and lower level of education, represent the group of women with the highest risk of moderate to severe low back pain during pregnancy and should be payed special attention., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Maternal smoking is still a major public health problem posing the risk of several negative health outcomes for both the pregnant woman and her offspring. The prevalence of maternal smoking in Denmark and other high-income countries has decreased continuously since the 1980s, and a prevalence below 10% of women who continue to smoke during pregnancy has been reported in studies after 2010. Previous studies have shown that low socioeconomic status is associated with maternal smoking. Information from the Danish Birth Register about maternal smoking shows that the prevalence of women who report to smoke in pregnancy has decreased continuously with 23.3% who reported ever smoking in pregnancy in 2000, 12.9% in 2010 and 9.0% in 2017. The aim of this study was to estimate the prevalence of maternal smoking at the time of conception and at 20 weeks of gestation in a regional Danish population, to describe differences in maternal characteristics among smokers, quitters and never-smokers, and to estimate predictors of smoking at the time of conception., Methods: A cross-sectional study was conducted among pregnant women receiving antenatal care at the Department of Obstetrics, Zealand University Hospital, Denmark from August 2015 to March 2016 (n = 566). The main outcome was smoking at the time of conception and at 20 weeks of gestation. The questionnaire also collected information about maternal, health-related and sociodemographic characteristics. Descriptive analysis was conducted, and multivariate logistic regression analysis was used to assess the potential associated predictors (adjusted odds ratio)., Results: The prevalence of self-reported smoking at the time of conception was 16% (n = 90) and 6% smoked at 20 weeks of gestation (n = 35), as 61% of smokers quit smoking during early pregnancy. Multiple logistic regression analysis showed that significant predictors for smoking at conception were the socioeconomic factors; ≤12 years of education, shift work and being unemployed., Conclusion: The prevalence of self-reported maternal smoking in this regional Danish population of pregnant women is lower than seen in previous studies. However, predictors for smoking at the time of conception remain to be factors of low socioeconomic status confirming a social inequality in maternal smoking. Women at risk of smoking during pregnancy must be identified in early pregnancy or even before pregnancy and be offered interventions to help them quit smoking.

Background and Objectives: The number of women of childbearing age with chronic diseases is rising. Evidence has shown that obstetric complications and poor psychological well-being are more prevalent among this group, in addition to these women reporting experiences of less than satisfactory care. More research is needed to investigate how to best meet the special needs of this group during pregnancy and postpartum. Previous research has shown that care coordination, continuity of care, woman-centered care, and specialized maternity care interventions delivered to women with high-risk pregnancies can improve patient-reported outcomes and pregnancy outcomes and be cost-effective. However, no previous trials have examined the efficacy and cost-effectiveness of such interventions among pregnant women with chronic diseases. This paper describes the protocol of a randomized controlled trial (RCT) of a midwife-coordinated, individualized and specialized maternity care intervention (ChroPreg) as an add-on to standard care for pregnant women with chronic diseases., Methods/design: This two-arm parallel group RCT will be conducted from October 2018 through June 2020 at the Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark. Pregnant women with chronic diseases are invited to participate; women will be randomized and allocated 1:1 to the ChroPreg intervention plus standard care or standard care alone. The ChroPreg intervention consists of three main components: (1) coordinated and individualized care, (2) additional ante- and postpartum consultations, and (3) specialized midwives. The primary outcome is length of hospital stay during pregnancy and in the postpartum period, and secondary outcomes are psychological well-being (five-item World Health Organization Well-Being Index, Edinburgh Postnatal Depression Scale, Cambridge Worry Scale), health-related quality of life (12-Item Short Form Health Survey), patient satisfaction (Pregnancy and Childbirth Questionnaire), number of antenatal contacts, and pregnancy and delivery outcomes. Data are collected via patient-administered questionnaires and medical records., Discussion: This trial is anticipated to contribute to the field of knowledge on which planning of improved antenatal, intra-, and postpartum care for women with chronic disease is founded., Trial Registration: ClinicalTrials.gov, NCT03511508 . Registered April 27, 2018.

Background: In Scandinavia, women of childbearing age represent nearly 50% of the overall workforce. Two-thirds of these women spend a considerable time on sick leave during their pregnancies. Low back pain accounts for a significant portion of all pregnancy-related sick leave. However, pregnant women's experiences with pain-induced sick leave remains unexplored., Objective: The study aimed to investigate women's experiences with sick leave in relation to pregnancy-induced low back pain., Methods: An inductive, qualitative study based on semi-structured, in-depth, face-to-face interviews with 19 purposefully selected Danish women. Interviews were analysed by means of thematic content analysis., Results: The analysis revealed 4 categories: (1) Stuck in a diagnosis, (2) Inflexibility of the labour market, (3) Adapting to reduced capacity for work, and (4) Being socially excluded. The women's experiences revolved around disruption of their physical functioning and expected capacity for work, a loss of professional identity, and a sense of inflexibility and exclusion from important relationships at work., Conclusions: Our findings illuminate the possibilities for workplace adjustments with the intention of reducing time spent on sick leave, maintaining pregnant women's affiliation with their workplace, and a need to explore the role of healthcare professionals in addressing women's supportive needs in relation to sick leave.

Background: Evidence has shown that there are several physical and mental advantages of exercise during pregnancy. Despite this, the recommendations for exercise during pregnancy are poorly fulfilled. The aim of this study was to illuminate non-exercising pregnant women's views and experiences concerning exercise before and during pregnancy., Method: The study had a qualitative design with an inductive approach and was analysed by content analysis. A total of 16 individual and face-to-face interviews were conducted with healthy pregnant women, mainly in the third trimester and living in Sweden. The participating women had not been exercising 3 months before pregnancy or during pregnancy., Results: The main category "Insurmountable now, but possible in the future" was based on the four categories: "Lost and lack of routines", "Feelings of inadequacy", "Having a different focus" and "Need for support". The women experienced that their lack of routines was a major barrier that prevented them from exercising. Other factors that contributed were, for example, pregnancy-related problems, long working days and prioritizing family life. The women described it as difficult to combine exercise with their focus on the pregnancy and they missed continuous support from the antenatal care provider. The women expressed a need for suggestions concerning exercise during pregnancy and follow-up on previous counselling, especially when pregnancy-related issues arose. Information about easily accessible alternatives or simple home exercises was requested. They felt immobile and were not satisfied with their inactivity and tried to partly compensate with everyday activities. The women identified the postpartum period as an important possibility for becoming more active, for their own sake, but also because they wanted to become role models for their children., Conclusion: Continuous support during pregnancy is needed concerning exercise. Pregnancy is mostly a barrier that prevents exercise for this group of women but, at the same time, may be a motivator and a possibility for better health. As the result showed that these women were highly motivated to a life-style change post-pregnancy, it may be crucial to support previously non-exercising women postpartum.

Background: Physical activity is one of the best documented activities with impacts on health in children and adults. Children born preterm show reduced physical and psychosocial function compared to children born at term. This may influence their level of physical activity. Reports on moderately preterm children's physical activities during childhood are limited. Thus, the aim of this study was to compare the leisure time physical activity at age 9-11 years of moderately preterm children with that of children born at term., Methods: Data from 4941 mother-child pairs from the Aarhus Birth Cohort (1989-91) were used. The cohort gathered clinical information, including gestational age at delivery. Information about parental socio-demographic and lifestyle factors was obtained from questionnaires completed during the second trimester of pregnancy. Information about children's physical activities was reported in a 9- to 11-year follow-up questionnaire completed by parents detailing how many times per week their child participated in sports activities outside of school, hours spent per week playing outside, and hours per week engaged in sedentary activities. Data were analysed using multiple logistic regression with the lowest activity group as a reference group., Results: A total of 158 children (3.2%) were born moderately preterm, i.e., between 32 and 36 completed weeks. Children born moderately preterm participated in sports activities as often as their peers born at term; they also participated in frequent sports activities (≥ 4 times per week) as often as their peers. There were no differences in hours per week spent playing outside or in sedentary activities between the two groups., Conclusions: Nine- to 11-year-old moderately preterm children participated in sports activities outside school to a similar extent as their peers and engaged in outdoor activities and sedentary activities for the same duration of time per week as their peers born at term.

Background: Information and communication technologies are increasingly used in health care to meet demands of efficiency, safety and patient-centered care. At a large Danish regional hospital, women report their physical, mental health and personal needs prior to their first antenatal visit. Little is known about the process of self-reporting health, and how this information is managed during the client-professional meeting., Aim: To explore women's experiences of self-reporting their health status and personal needs online prior to the first midwifery visit, and how this information may affect the meeting between the woman and the midwife., Method: Fifteen semi-structured interviews with pregnant women and 62h of observation of the first midwifery visit were carried out. Conventional content analysis was used to analyse data., Findings: Three main categories were identified; 'Reporting personal health', 'Reducing and generating risk', and 'Bridges and gaps'. Compared to reporting physical health information, more advanced levels of health literacy might be needed to self-assess mental health and personal needs. Self-reporting health can induce feelings of being normal but also increase perceptions of pregnancy-related risk and concerns of being judged by the midwife. Although women want to have their self-reported information addressed, they also have a need for the midwife's expert knowledge and advice, and of not being perceived as a demanding client., Conclusion: Self-reported health prior to the first midwifery visit appears to have both intended and unintended effects. During the midwifery visit, women find themselves navigating between competing needs in relation to use of their self-reported information., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)