Preterm Birth Following Active Surveillance vs Loop Excision for Cervical Intraepithelial Neoplasia Grade 2.

Importance: Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) is being implemented in many high-income countries due to the association of excisional treatment with preterm birth. However, it is unknown whether active surveillance results in lower risk of preterm birth given that cervical dysplasia itself is associated with higher risk of preterm birth. Objective: To compare the preterm birth risk between women with CIN2 undergoing active surveillance or immediate loop electrosurgical excision procedure (LEEP). Design, Setting, and Participants: This historical population-based cohort study included women with a first-time diagnosis of CIN2 and a subsequent singleton birth from 1998 to 2018 in Denmark. Women with prior CIN grade 3 or greater or LEEP were excluded. Data were collected from 4 Danish health care registries. Analyses were conducted from October 2022 to June 2023. Exposure: Women were categorized into active surveillance (cervical biopsy and/or cytology) or immediate LEEP based on their first cervical sample after CIN2 diagnosis. The active surveillance group was further subdivided based on whether a delayed LEEP was performed within 28 months from CIN2 diagnosis. Main Outcomes and Measures: Risk of preterm birth (<37 + 0 weeks) was assessed and relative risks (RRs) were calculated using modified Poisson regression. Analyses used inverse probability treatment weighting of the propensity scores to adjust for age, parity, calendar year, index cytology, and smoking. Results: A total of 10 537 women with CIN2 and a singleton birth were identified; 4430 (42%) underwent active surveillance and 6107 (58%) were treated with immediate LEEP. For both groups, most were aged 23 to 29 years at CIN2 diagnosis (3125 [70%] and 3907 [64%], respectively). Overall, 869 births (8.2%) were preterm. The risk of preterm birth was comparable between active surveillance and immediate LEEP (RR, 1.03; 95% CI, 0.90-1.18). However, for women undergoing delayed LEEP after active surveillance (1539 of the active surveillance group [35%]), the risk of preterm birth was higher than for women treated with immediate LEEP (RR, 1.29; 95% CI, 1.08-1.55). Conclusions and relevance: In this cohort study of women with CIN2, the risk of preterm birth was comparable between active surveillance and immediate LEEP. However, delayed LEEP was associated with 30% higher risk of preterm birth than immediate LEEP. Thus, risk stratification at CIN2 diagnosis is important to identify women with increased risk of delayed LEEP.

Breastfeeding among parous women offered home-visit by a midwife after early discharge following planned cesarean section: Secondary analysis of a randomized controlled trial.

INTRODUCTION: Early discharge holds several advantages and seems safe after planned cesarean section among low-risk women. However, breastfeeding rates are lower after cesarean section. Thus, concern has been raised that early discharge among these women may affect breastfeeding even further. Therefore, we aimed to assess the effect of early discharge the day after planned cesarean section on breastfeeding, among parous women when a home-visit by a midwife was provided the day after discharge. METHODS: We conducted a secondary analysis of a randomized trial. Parous women (n=143) planned for cesarean section were allocated to either discharge within 28 hours after planned cesarean section followed by a home visit the day after (early discharge) or discharge at least 48 hours after planned cesarean section (standard care). The participants filled in questionnaires approximately 2 weeks before delivery and 1 week, 4 weeks, and 6 months postpartum. RESULTS: The proportions of women initiating breastfeeding were 84% versus 87% (early discharge vs standard care). After 6 months, 23% versus 21% were exclusively breastfeeding, while 29% versus 42% were partially breastfeeding. The mean duration of exclusive breastfeeding was 3.4 months (SD=2.3) in both groups. None of these differences was statistically significant. In both groups, the women's breastfeeding self-efficacy score before cesarean section correlated with the duration of breastfeeding. After 4 weeks, low-score rates were 28% versus 30%. CONCLUSIONS: Early discharge with follow-up home visits by a midwife after planned cesarean section in parous women is feasible without compromising breastfeeding.

Cardiac arrest during hyperacute caesarean section due to peripartum cardiomyopathy.

Peripartum cardiomyopathy is a rare and potentially dangerous form of heart failure presenting in women in the last month of pregnancy until five months post partum. The pathogenesis is believed to be multifactorial. This case report describes a young woman with adiposity and preeclampsia who was admitted to hospital and whose clinical condition quickly deteriorated. During the emergency caesarian section, the woman suffered a cardiac arrest and was successfully resuscitated. Echocardiography showed heart failure with an ejection fraction less-than 45% confirming the diagnosis of peripartum cardiomyopathy.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Length of hospital stay after cesarean section in Denmark from 2004 to 2016: A national register-based study.

INTRODUCTION: Length of hospital stay after birth has decreased during the last decades, but nationwide data on length of hospital stay after cesarean section are lacking. Elements of Enhanced Recovery Programs were reported to reduce the length of hospital stay. The aim of this nationwide study was to describe the length of hospital stay after cesarean section in Denmark from 2004 to 2016 taking into account birth- and health-related factors as well as demographic changes and, further, to assess potential differences between the five Danish regions. MATERIAL AND METHODS: Length of hospital stay was assessed in 164 209 deliveries by cesarean section in Denmark from 2004 to 2016. Data were obtained from the Danish National Patient Register. All deliveries by cesarean section at gestational age <22 weeks were excluded. Median length of hospital stay was reported based on crude and adjusted analyses. RESULTS: The median length of hospital stay was significantly reduced by 39 hours (95% confidence interval [CI] 37.9-40.1), from 97 hours (4.0 days) in 2004 to 58 hours (2.4 days) in 2016. Reductions were observed among both planned and emergency cesarean sections. When birth- and health-related factors as well as demographic changes were accounted for, median length of hospital stay was reduced by 30 hours (95% CI 29.3-30.8) in the period. The decrease in length of hospital stay from 2004 to 2016 varied between the five Danish regions, with adjusted reductions between 19 and 46 hours. CONCLUSIONS: A nationwide decrease in length of hospital stay after cesarean section was observed from 2004 to 2016 across all five regions but with significant regional variations. Further studies on the optimal length of hospital stay are needed, especially with regard to implementation of enhanced recovery programs.

Effect of early discharge after planned cesarean section on recovery and parental sense of security. A randomized clinical trial.

INTRODUCTION: In some European countries, discharge the day after planned cesarean section has become an accepted procedure. However, little is known about the patients' perception of early discharge. The aim of this study was to compare early discharge with standard care in relation to parental sense of security. Further, we evaluated postoperative pain, mobilization, and readmission. MATERIAL AND METHODS: We performed a randomized clinical trial including parous, singleton pregnant women with a planned cesarean section at term. The women were allocated to either discharge within 28 hours (intervention group) or after 48 hours (standard care group) following the cesarean section. Women discharged within 28 hours after cesarean section were offered a home visit by a midwife the following day. The primary outcome was the postnatal sense of security, which was reported by the woman and her partner in the "Parents' Postnatal Sense of Security" questionnaire 1 week postpartum. Secondary outcomes were pain score, use of analgesics, mobilization, readmission, and contacts with the healthcare system in the postoperative period. RESULTS: We included 143 women, of whom 72 were allocated to the intervention group and 71 were allocated to the standard care group. There were no differences in baseline characteristics. The two groups did not differ concerning the postnatal sense of security for the women (P = .98) or the postnatal sense of security for the partners (P = .38). We found no difference in pain scores, step count, use of analgesics, or number of contacts with the health-care system between the groups. CONCLUSIONS: Parental postnatal sense of security is not compromised by discharge within 28 hours followed by a home visit compared with discharge after 48 hours after planned cesarean section among parous women.

Cervical collagen is reduced in non-pregnant women with a history of cervical insufficiency and a short cervix.

INTRODUCTION: Preterm cervical shortening and cervical insufficiency may be caused by a constitutional weakness of the cervix. The aim of this study was to assess the cervical collagen concentration in non-pregnant women with a history of cervical insufficiency or of a short cervix in the second trimester of pregnancy. MATERIAL AND METHODS: In this case-control study we included non-pregnant women one year or more after pregnancy: 55 controls with a history of normal delivery; 27 women with a history of cervical insufficiency; and 10 women with a history of a short cervix (<5th percentile) and 10 women with a history of a long cervix (>95th percentile) at gestational weeks 18-20. We obtained biopsies (3 × 3-4 mm) from the ectocervix and determined the collagen concentration by measuring the hydroxyproline concentration. RESULTS: Women with cervical insufficiency had lower collagen concentrations (63.5 ± 5.1%; mean ± SD) compared with controls (68.2 ± 5.4%; p = 0.0004); area under the ROC curve 0.73 (95% CI 0.62-0.84). A cut-off value at 67.6% collagen resulted in a positive likelihood ratio of 3.2, a sensitivity of 60%, and a specificity of 81%. Also, women with a short cervix in the second trimester had lower collagen concentrations in a non-pregnant state (62.1% ± 4.9%) compared with women with a long cervix (67.8% ± 5.0%; p = 0.02). CONCLUSIONS: Both cervical insufficiency and a short cervix in the second trimester of pregnancy are associated with low cervical collagen concentrations in a non-pregnant state more than one year after pregnancy.

Recurrence rates after abdominal and vaginal cerclages in women with cervical insufficiency: a validated cohort study.

PURPOSE: To estimate the incidence of cervical insufficiency and compare recurrence rates of second trimester miscarriage/delivery in second and third pregnancies after prophylactic vaginal cerclage, abdominal cerclage, or no cerclage. METHODS: Retrospective chart review of a representative register-based sample of 621 women with a spontaneous second trimester miscarriage/delivery in the first pregnancy in Denmark (1997-2012). We used strict criteria for the diagnosis of cervical insufficiency. The outcome of subsequent pregnancies was described by treatment with prophylactic vaginal cerclage, abdominal cerclage, or no prophylactic cerclage. Women were followed until June 2015. RESULTS: Of 621 women, 149 (24%) fulfilled the strict criteria of cervical insufficiency. Prophylactic treatment with abdominal cerclage (n = 20), vaginal cerclage (n = 59), and no prophylactic cerclage (n = 61) resulted in a second pregnancy ending before 28 weeks in 5, 30, and 72% (p < 0.001) and before 34 weeks in 10, 46, and 84% (p < 0.001), respectively. Take-home baby rate was 95% after abdominal cerclage, 73% after vaginal cerclage, and 33% after no cerclage. In a third pregnancy, abdominal cerclage (n = 47), vaginal cerclage (n = 38), and no cerclage (n = 8) resulted in pregnancy ending before 34 weeks of gestation in 2, 21, and 25%, respectively (p = 0.01). CONCLUSIONS: Cervical insufficiency was diagnosed in 24% of women with an initial second trimester spontaneous miscarriage/delivery. In second and third pregnancies, recurrence rates were significantly lower after prophylactic vaginal or abdominal cerclage compared with no cerclage.

RETRACTED: Long-term follow-up after abdominal cerclage: A population-based cohort study.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and the Authors as the Authors failed to request and receive permission to use the data from Aarhus Hospital.

Recurrence of second trimester miscarriage and extreme preterm delivery at 16-27 weeks of gestation with a focus on cervical insufficiency and prophylactic cerclage.

INTRODUCTION: The objective of this study was to describe recurrence rates of second trimester miscarriage and extreme preterm delivery by phenotype and use of prophylactic cerclage in a register-based cohort. MATERIAL AND METHODS: We included women with a first second trimester miscarriage or extreme preterm delivery (16+0 to 27+6 gestational weeks) in Denmark in 1997-2012 (n = 9602) by combined use of the Danish Medical Birth Register and the Danish National Patient Register. Eight phenotypes were identified by ICD-10 codes in a hierarchy with the following sequence: major fetal anomaly, multiple gestation, uterine anomaly, placental insufficiency, antepartum bleeding, cervical insufficiency, preterm premature rupture of membranes, and intrauterine fetal death. Recurrence rate after a second trimester miscarriage/spontaneous delivery in the period was calculated based on the register data. In cervical insufficiency outcome was stratified by prophylactic cerclage applied <16 weeks of gestation. RESULTS: Overall recurrence rate was 7.3% (n = 452), a rate that differed by phenotype from <5% (fetal anomaly, multiple gestations, intrauterine fetal death) to 21% (cervical insufficiency). In women with cervical insufficiency the recurrence rate was 28% without cerclage; vaginal cerclage was associated with a significant reduction [adjusted odds ratio (OR) 0.47; 95% CI 0.29-0.76] and abdominal cerclage with an even greater reduction (adjusted OR 0.14; 95% CI 0.03-0.61). CONCLUSIONS: The overall recurrence rate of second trimester miscarriage or extreme preterm delivery was 7%, but it differed significantly by phenotype. The highest rate, 28%, was found in cervical insufficiency, and prophylactic cerclage was associated with a significant reduction in recurrence.

Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency.

OBJECTIVE: To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 (MBL2), collagen1α1 (COL1A1), factor II and factor V Leiden genes. METHODS: In a case-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. RESULTS: Homozygous carriers of the interleukin 6 (IL6) -174 genotype GG had an odds ratio (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and MBL2 genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than in controls (median 408 and 1,985 ng/ml, respectively, p < 0.01). CONCLUSIONS: Single nucleotide polymorphisms in the IL6 gene and the MBL2 gene and low MBL levels related to the latter polymorphism may increase the risk of preterm birth due to cervical insufficiency.

Validation of second trimester miscarriages and spontaneous deliveries.

OBJECTIVE: To validate the diagnosis of second trimester miscarriages/deliveries (16+0 weeks to 27+6 weeks of gestation) recorded as miscarriages in the Danish National Patient Registry or spontaneous deliveries in the Danish Medical Birth Registry, and asses the validity of risk factors, pregnancy complications, and cerclage by review of medical records. MATERIALS AND METHODS: In a cohort of 2,358 women with a second trimester miscarriage/delivery in first pregnancy and a subsequent delivery during 1997-2012, we reviewed a representative sample of 682 medical records. We searched for clinically important information and calculated positive predictive values of the registry diagnoses stratified by type of registry, as well as sensitivity, specificity, positive predictive value, and kappa coefficients of risk factors, pregnancy complications, and cerclage. RESULTS: Miscarriage/spontaneous delivery in the second trimester was confirmed in 621/682 patients (91.1%). Pregnancy complications in second trimester miscarriages were underreported, resulting in low sensitivities and poor to moderate agreements between records and registries. There was a good agreement (kappa >0.6) between medical records and the registries regarding risk factors and cerclage. The diagnosis of cervical insufficiency had "moderate" kappa values for both miscarriages and deliveries (0.55 and 0.57). CONCLUSION: Spontaneous second trimester deliveries and miscarriages recorded in the registers were confirmed by medical records in 91%, but register-based information on pregnancy complications need to be improved. We recommend that all pregnancies ending spontaneously beyond the first trimester are included in the national birth registry and described by appropriate variables.

Cervical collagen concentration within 15 months after delivery.

OBJECTIVE: Cervical collagen concentration decreases during pregnancy. The increased risk of preterm birth after a short interpregnancy interval may be explained by an incomplete remodeling of the cervix. The objective of this study was to describe the changes in cervical collagen concentration over 15 months after delivery. STUDY DESIGN: The collagen concentrations were determined in cervical biopsy specimens that were obtained from 15 women at 3, 6, 9, 12, and 15 months after delivery. RESULTS: The mean cervical collagen concentrations were 50%, 59%, 63%, 65%, and 65% of dry weight (SD, 4.2-6.5). This increase was statistically significant until month 9, but not between months 9 and 12. CONCLUSION: Low collagen concentrations in the uterine cervix may contribute to the association between a short interpregnancy interval and preterm birth.