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.

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.

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.

Outcome of subsequent pregnancies in women with complete uterine rupture: A population-based case-control study.

INTRODUCTION: In the attempt of a trial of labor after a cesarean section approximately one in 200 women experience a complete uterine rupture. As a complete uterine rupture is associated with an adverse perinatal outcome, data regarding subsequent pregnancies are needed to provide proper care and guidance to women with a complete uterine rupture when informing them of future possibilities. The objective of this study was to investigate the fetal and maternal outcomes in subsequent pregnancies after a complete uterine rupture. MATERIAL AND METHODS: Retrospective population-based case-control study. Denmark 1997-2017. A total of 175 women with complete uterine rupture during an attempted trial of labor after cesarean (TOLAC) at term (cases) and a corresponding group of 272 women with no uterine rupture during an attempted TOLAC at term (controls) were labeled as index deliveries. Index deliveries were included from January 1, 1997 to December 31, 2008. From the date of the index delivery to December 31, 2017 the information on subsequent pregnancies and deliveries, and on referral to hospital with any obstetric or gynecological diagnosis were retrieved from the Danish Medical Birth Registry and National Patient Registry. Main outcome measures were miscarriage, perinatal death, neonatal morbidity, preterm birth, and recurrence of uterine rupture. Outcome measures were compared between cases and controls. RESULTS: After the index deliveries; there were 109 pregnancies and 70 deliveries after gestational age 22+0  weeks in the population of cases. In the population of controls, there were 183 pregnancies and 126 deliveries after 22+0  weeks. Cases had a significantly higher risk of miscarriage (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.36-13.17). The incidence of uterine rupture was 8.6% among cases and 0.8% among controls (OR 11.7; 95% CI 1.36-543.1). Among cases, 98.6% had live-born infants, and none of these had severe neonatal morbidity. No significant association was found between previous complete uterine rupture and preterm delivery, placenta previa, hysterectomy in relation to subsequent births, diagnosis such as meno/metrorrhagia, dysmenorrhea, or procedures such as hysteroscopy or hysterectomy. CONCLUSIONS: In pregnancies following complete uterine rupture continuing after 22+0  weeks, maternal and fetal outcomes are good when managed promptly with cesarean delivery.

Gender incongruence in Denmark, a quantitative assessment.

INTRODUCTION: The number of persons with gender incongruence referred to health care is increasing, but national data on the incidence of gender incongruence are lacking. The aim of this study was to quantify the development in number of individuals with gender incongruence over time and to estimate the national incidence in Denmark. MATERIAL AND METHODS: Historical descriptive cohort study. Individuals older than 18 years with legal sex-change in their person registration number were achieved from Statistics Denmark, and the National Health Register provided data on contact diagnoses related to gender-identity conditions. By combining these two data sources, we made estimates on incidence and incidence rates for individuals with gender incongruence in Denmark through a 41-year period 1980-2020. RESULTS: Through 1980-2020, the annual number of legal sex-changes increased in individuals assigned female at birth from 5 to approximately 170 and among individuals assigned male at birth from 10 to approximately 150. The cumulative number of legal sex-changes at the end of 2019 was 1275 assigned female at birth and 1422 assigned male at birth and 66% of the legal sex-changes were in individuals below 30 years. Correspondingly, the annual number of contacts with the healthcare system due for gender-identity-related conditions increased from 30 during 1990-1999 to around 500 in 2017 (both genders combined), with a 10-fold increase from 2010 to 2017. CONCLUSIONS: The number of legal sex-changes and healthcare contacts due to gender-identity-related diagnoses increased substantially over the last 40 years with a more than 10-fold increase during the last decade. This calls for research on possible explanations for this increase, for research on the short-term and long-term health consequences of hormonal and surgical treatment regimens and for ensuring adequate healthcare facilities.

Pregnancy loss: A 40-year nationwide assessment.

INTRODUCTION: Pregnancy loss is frequent. We aimed to assess the frequency and trends in pregnancy losses according to female age and mode of conception over a 40-year follow-up period. MATERIAL AND METHODS: In a national historical prospective cohort study, we followed all Danish women 10-49 years over the 40-year study period 1978-2017. Data on pregnancies and their outcomes were obtained from the National Health Registry, the Medical Birth Registry and the National Fertility Registry. Incidence rates per 100 pregnancies and per 1,000 women-years as well as lifetime risks per 100 women were calculated. Women included in the lifetime analysis were followed from age 12 to age 49. Pregnancy loss included spontaneous abortion, missed abortion and anembryonic pregnancy. RESULTS: In 3 519 455 recorded pregnancies, 337 008, or 9.6%, were diagnosed with a pregnancy loss. The proportion increased from 7.5% in 1978-1979, peaked at 10.7% in 2000 and thereafter decreased to 9.1% in 2015-2017. Pregnancy loss rate in women 10-14 years was 3.9%, increasing gradually with age to 26.9% in pregnant women 45-49 years, a 6.9-fold increase. Loss rates were slightly lower in naturally conceived pregnancies than in assisted pregnancies except for women above 45 years, where the risk of loss was higher in the spontaneously conceived group. Lifetime risk of specific numbers of losses were: 0: 76.9%, 1: 17.9%, 2: 3.9%, 3: 0.87%, and 4+: 0.35%. CONCLUSIONS: The proportion of women experiencing pregnancy loss has changed little throughout four decades and is still primarily influenced by female age. More than 75% of pregnant women are never recorded with a pregnancy loss, and <1.5% will experience three or more losses.

Is cesarean section a cause of affective disorders?-A national cohort study using sibling designs.

BACKGROUND: The gut microbiota of children delivered by cesarean section differs from that of children delivered vaginally. In light of the gut-brain axis hypothesis, cesarean section may influence risk of affective disorders. METHODS: Population based prospective cohort study included Danish children born 1982 through 2001, with follow-up until 2015. The effect of delivery mode on the risk of affective disorders was assessed using a standard Cox model and two types of Cox sibling models. Diagnostic codes or prescriptions for antidepressants and lithium were used to define cases of affective disorders. RESULTS: 1,009,444 children were followed for 8,880,794 person-years from the age of 13 years, with relevant covariates available from birth. There are strong calendar time trends in the occurrence of affective disorders with an increasingly younger age at first diagnosis and with a hotspot between the years 2007-2012. Fully adjusted standard Cox models showed an increased risk of affective disorders for both pre-labor (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.08-1.15) and intrapartum (HR, 1.07; 95% CI, 1.05-1.10) cesarean section, compared to vaginal delivery. This effect disappeared in the between-within sibling model for pre-labor (HR, 1.00; 95% CI, 0.94-1.07) but not intrapartum (HR, 1.05; 95% CI, 1.00-1.12) cesarean section. LIMITATIONS: Interpretation of results from sibling models may not be relevant to children without siblings. CONCLUSIONS: These results do not support the hypothesis that a delivery-mode dependent change in gut microbiota is a cause of subsequent affective disorders, despite an apparent association with delivery mode.

Reduced Complications Following Implementation of Laparoscopic Hysterectomy: A Danish Population-based Cohort Study of Minimally Invasive Benign Gynecologic Surgery between 2004 and 2018.

STUDY OBJECTIVE: To monitor and report nationwide changes in the rates of and complications after different methods for benign hysterectomy, operative hysteroscopy, myomectomy, and embolization in Denmark. To report the national mortality after benign hysterectomy DESIGN: National prospective, observational cohort study. SETTING: The Danish Hysterectomy and Hysteroscopy Database. PATIENTS: Women undergoing surgery for benign gynecologic diseases: 64 818 hysterectomies, 84 175 hysteroscopies, 4016 myomectomies, and 1209 embolizations in Denmark between 2004 and 2018. INTERVENTIONS: National meetings with representatives from all departments, annual working reports of institutional complication rates, workshops, and national guideline initiative to improve minimally invasive surgical methods. MEASUREMENTS AND MAIN RESULTS: Rates of the different methods and complications after each method with follow-up to 5 years as recorded by the database directly in the National Patient Registry. Nationwide, a decline in the use of hysterectomy, myomectomy, embolizations, and endometrial ablation. The total short-term complications were 9.8%, 7.5%, 8.9%, and 2.7% respectively, however, with a persistent risk of approximately 20% for recurrent operations within 5 years after endometrial ablation. Initially, we urged for increased use of vaginal hysterectomy, but only reached 36%. From 2010, we urged for reducing abdominal hysterectomies by implementing laparoscopic hysterectomy and reached 72% laparoscopic and robotic procedures. Since 2015, we used coring or contained morcellation for removal of large uterus at laparoscopic hysterectomy. The major and minor complication rates (modified Clavien-Dindo classification) were reduced significantly from 8.1% to 4.1% and 9.9% to 5.7% respectively. Mortality after benign hysterectomy was 0.27‰. The odds ratio for major complications after abdominal hysterectomy was 1.66 (1.52-1.81) compared to minimally invasive hysterectomy independent of the length of stay, high-volume departments, indications, comorbidity, age, and calendar year. CONCLUSION: Fifteen years with a national database has resulted in a marked quality improvement. Denmark has 85% minimally invasive hysterectomies and has reduced the number of major complications by 50%.

Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder.

BACKGROUND: Increasing attention deficit hyperactivity disorder (ADHD) incidence has been proposed to be caused by factors influencing microbiota in early life. We investigated the potential causality between ADHD and two surrogate markers for changes in children's microbiota: birth delivery mode and early childhood antibiotic use. METHOD: This population-based, prospective cohort study linked nationwide registers of data for native Danish singleton live births in Denmark from 1997 to 2010. Exposure variables were delivery mode and antibiotic use during the first 2 years of life. The main outcome measure was ADHD diagnosis or redeemed ADHD medication prescriptions. For statistical analysis, we used both advanced sibling models and a more traditional approach. RESULTS: We included 671,592 children, followed from their second birthday in the period 1999-2014 for 7,300,522 person-years. ADHD was diagnosed in 17,971. In total, 17.5% were born by cesarean delivery, and 72% received antibiotic treatment within their first 2 years of life. In the adjusted between-within sibling survival model, mode of delivery or antibiotics had no effect on ADHD when compared with vaginal delivery or no antibiotic treatment as hazard ratios were 1.09 (95% confidence interval 0.97-1.24) for intrapartum cesarean, 1.03 (0.91-1.16) for prelabor cesarean, 0.98 (0.90-1.07) for penicillin, and 0.99 (0.92-1.06) for broader spectrum antibiotics. In a sibling-stratified Cox regression, intrapartum cesarean was associated with increased ADHD risk, but other exposures were not. In a descriptive, nonstratified Cox model, we found increased risk for ADHD for all exposures. CONCLUSIONS: Detailed family confounder control using the superior between-within model indicates that cesarean delivery or use of antibiotics during the first 2 years of life does not increase ADHD risk. Therefore, our study suggests that changes in children's microbiota related to cesarean delivery or antibiotic use, do not cause ADHD.

Relation Between Infant Microbiota and Autism?: Results from a National Cohort Sibling Design Study.

BACKGROUND: Hypotheses concerning adverse effects of changes in microbiota have received much recent attention, but unobserved confounding makes them difficult to test. We investigated whether surrogate markers for potential adverse microbiota change in infancy affected autism risk, addressing unobserved confounding using a sibling study design. METHODS: This is a population-based, prospective cohort study including all singleton live births in Denmark from 1997 to 2010. The exposure variables were cesarean delivery and antibiotic use in the first 2 years of life. The outcome was a subsequent autism diagnosis. We used the between- and within-sibling model and compared it with sibling-stratified Cox models and simpler standard Cox models that ignored sibship. RESULTS: Of our study population including 671,606 children, who were followed for up to 15 years (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted that both cesarean (compared with vaginal) delivery and antibiotics increased the risk of autism. In the sibling-stratified Cox model, only broader spectrum antibiotics were associated with increased risk of autism: hazard ratio (HR) = 1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18); and broader spectrum antibiotics HR = 1.05 (0.95, 1.16). CONCLUSIONS: The between-within model rendered more precise estimates than sibling-stratified Cox models, and we believe that it also provided more valid estimates. Results from these preferred models do not support a causal relation between antibiotic treatment during infancy, cesarean delivery, and autism. See video abstract at, http://links.lww.com/EDE/B432.

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 109, Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

Postpartum urinary tract infection by mode of delivery: a Danish nationwide cohort study.

OBJECTIVES: To examine the association between postpartum urinary tract infection and intended mode of delivery as well as actual mode of delivery. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: All live births in Denmark between 2004 and 2010 (n=450 856). Births were classified by intended caesarean delivery (n=45 053) or intended vaginal delivery (n=405 803), and by actual mode of delivery: spontaneous vaginal delivery, operative vaginal delivery, emergency or planned caesarean delivery in labour or prelabour. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was postpartum urinary tract infection (n=16 295) within 30 days post partum, defined as either a diagnosis of urinary tract infection in the National Patient Registry or redemption of urinary tract infection-specific antibiotics recorded in the Register of Medicinal Product Statistics. RESULTS: We found that 4.6% of women with intended caesarean delivery and 3.5% of women with intended vaginal delivery were treated for postpartum urinary tract infection.Women with intended caesarean delivery had a significantly increased risk of postpartum urinary tract infection compared with women with intended vaginal delivery (OR 1.33, 95% CI 1.27 to 1.40), after adjustment for age at delivery, smoking, body mass index, educational level, gestational diabetes mellitus, infection during pregnancy, birth weight, preterm delivery, preterm prelabour rupture of membranes, pre-eclampsia, parity and previous caesarean delivery (adjusted OR 1.24, 95% CI 1.17 to 1.46).Using actual mode of delivery as exposure, all types of operative delivery had an equally increased risk of postpartum urinary tract infection compared with spontaneous vaginal delivery. CONCLUSIONS: Compared with intended vaginal delivery, intended caesarean delivery was significantly associated with a higher risk of postpartum urinary tract infection. Future studies should focus on reducing routine catheterisation prior to operative vaginal delivery as well as improving procedures related to catheterisation.

Early postnatal hyperglycaemia is a risk factor for treatment-demanding retinopathy of prematurity.

BACKGROUND: To investigate whether neonatal hyperglycaemia in the first postnatal week is associated with treatment-demanding retinopathy of prematurity (ROP). METHODS: This is a Danish national, retrospective, case-control study of premature infants (birth period 2003-2006). Three national registers were searched, and data were linked through a unique civil registration number. The study sample consisted of 106 cases each matched with two comparison infants. Matching criteria were gestational age (GA) at birth, ROP not registered and born at the same neonatal intensive care unit. Potential 'new' risk factors were analysed in a multivariate logistic regression model, while adjusted for previously recognised risk factors (ie, GA at birth, small for gestational age, multiple birth and male sex). RESULTS: Hospital records of 310 preterm infants (106 treated; 204 comparison infants) were available. Nutrition in terms of energy (kcal/kg/week) and protein (g/kg/week) given to the preterm infants during the first postnatal week were statistically insignificant between the study groups (Mann-Whitney U test; p=0.165/p=0.163). Early postnatal weight gain between the two study groups was borderline significant (t-test; p=0.047). Hyperglycaemic events (indexed value) were statistically significantly different between the two study groups (Mann-Whitney U test; p<0.001). Hyperglycaemia was a statistically independent risk factor (OR: 1.022; 95% CI 1.002 to 1.042; p=0.031). CONCLUSION: An independent association was found between the occurrence of hyperglycaemic events during the first postnatal week and later development of treatment-demanding ROP, when adjusted for known risk factors.

Epidemiological factors associated with ESBL- and non ESBL-producing E. coli causing urinary tract infection in general practice.

The purpose of the study was to evaluate how use of antibiotics precedes the presence of ESBL-producing E.coli in general practice. The authors performed a triple-case-control study where three case groups were individually compared to a single control group of uninfected individuals. Urine samples were prospectively collected and retrospective statistical analyses were done. This study included 98 cases with urinary tract infection (UTI) caused by ESBL-producing E. coli, 174 with antibiotic-resistant (non-ESBL) E. coli, 177 with susceptible E. coli and 200 with culture negative urine samples. Case groups had significantly higher use of antibiotics than the control group within 30 days before infection (p < 0.0001). The ESBL group had significantly more hospital admissions than the other case groups (p < 0.05). Hospital admission was an independent risk factor for community onset UTI by ESBL-producing E. coli. Exposure to antibiotics was a risk factor for UTI with E. coli, while prior antibiotic usage was not an indisputable predictor for infection with ESBL-producing E.coli in general practice.