Conservative management or cesarean hysterectomy for placenta accreta spectrum: the PACCRETA prospective study.

BACKGROUND: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management. OBJECTIVE: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ). STUDY DESIGN: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias. RESULTS: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy. CONCLUSION: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy.

Measuring severe neonatal morbidity using hospital discharge data in France.

BACKGROUND: Measuring infant health at birth is key for surveillance and research in obstetrics and neonatology, but there is no international consensus on morbidity indicators. The Neonatal Adverse Outcome Indicator (NAOI) is a composite indicator, developed in Australia, which measures the burden of severe neonatal morbidity using hospital discharge data. OBJECTIVE: To evaluate the applicability of the NAOI in France for surveillance and research. METHODS: We constituted a cohort of live births ≥24 weeks' gestational age in Metropolitan France from 2014 to 2015 using hospital discharge, insurance claims and cause of death data. Outlier hospitals were identified using funnel plots of standardised morbidity ratios (SMR), and their coding patterns were assessed. We compared the NAOI and its component codes with published Australian and English data and estimated unadjusted and adjusted risk ratios for known risk factors for neonatal morbidity. RESULTS: We included 1,459,123 births (511 hospitals). Twenty-eight hospitals had SMR above funnel plot control limits. Newborns with NAOI morbidities in these hospitals had lower mortality and shorter stays than in other hospitals. Amongst within-limit hospitals, NAOI prevalence was 4.8%, comparable to Australia (4.6%) and England (5.4%). Most individual components had a similar prevalence, with the exception of respiratory support, intravenous fluid procedures and infection. NAOI was lowest at 39 weeks (2.2%) with higher risks for maternal age ≥40 (relative risk [RR] 1.47, 95% confidence interval [CI] 1.42, 1.51), state medical insurance (RR 1.60, 95% CI 1.52, 1.68), male sex (RR 1.21, 95% CI 1.19, 1.23) and birthweight <3rd percentile (RR 4.60, 95% CI 4.51, 4.69). CONCLUSIONS: The NAOI provides valuable information on population prevalence of severe neonatal morbidity and its risk factors. Whilst the prevalence was similar in high-income countries with comparable neonatal mortality levels, ensuring valid comparisons between countries and hospitals will require further work to harmonize coding procedures, especially for infection and respiratory morbidity.

Impact of the SARS-CoV-2 pandemic and first lockdown on pregnancy monitoring in France: the COVIMATER cross-sectional study.

BACKGROUND: In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, consultations and pregnancy monitoring examinations had to be reorganised urgently. In addition, women themselves may have postponed or cancelled their medical monitoring for organisational reasons, for fear of contracting the disease caused by SARS-CoV-2 (COVID-19) or for other reasons of their own. Delayed care can have deleterious consequences for both the mother and the child. Our objective was therefore to study the impact of the SARS-CoV-2 pandemic and the first lockdown in France on voluntary changes by pregnant women in the medical monitoring of their pregnancy and the associated factors. METHODS: A cross-sectional study was conducted in July 2020 using a web-questionnaire completed by 500 adult (> 18 years old) pregnant women during the first French lockdown (March-May 2020). A robust variance Poisson regression model was used to estimate adjusted prevalence ratios (aPRs). RESULTS: Almost one women of five (23.4%) reported having voluntarily postponed or foregone at least one consultation or pregnancy check-up during the lockdown. Women who were professionally inactive (aPR = 1.98, CI95%[1.24-3.16]), who had experienced serious disputes or violence during the lockdown (1.47, [1.00-2.16]), who felt they received little or no support (1.71, [1.07-2.71]), and those who changed health professionals during the lockdown (1.57, [1.04-2.36]) were all more likely to have voluntarily changed their pregnancy monitoring. Higher level of worry about the pandemic was associated with a lower probability of voluntarily changing pregnancy monitoring (0.66, [0.46-0.96]). CONCLUSIONS: Our results can guide prevention and support policies for pregnant women in the current and future pandemics.

Composite neonatal morbidity indicators using hospital discharge data: A systematic review.

BACKGROUND: Neonatal morbidity is associated with lifelong impairments, but the absence of a consensual definition and the need for large data sets limit research. OBJECTIVES: To inform initiatives to define standard outcomes for research, we reviewed composite neonatal morbidity indicators derived from routine hospital discharge data. DATA SOURCES: PubMed (updated on October 12, 2018). The search algorithm was based on three components: "morbidity," "neonatal," and "hospital discharge data." STUDY SELECTION AND DATA EXTRACTION: Studies investigating neonatal morbidity using a composite indicator based on hospital discharge data were included. Indicators defined for specific conditions (eg congenital anomalies, maternal addictions) were excluded. The target population, objectives, component morbidities, diagnosis and procedure codes, validation methods, and prevalence of morbidity were extracted. SYNTHESIS: For each study, we assessed construct validity by describing the methods used to select the indicator components and evaluated whether the authors assessed internal and external validity. We also calculated confidence intervals for the prevalence of the morbidity composite. RESULTS: Seventeen studies fulfilled inclusion criteria. Indicators targeted all (n = 4), low-/moderate-risk (n = 9), and very preterm (VPT, n = 4) infants. Components were similar for VPT infants, but domains and diagnosis codes within domains varied widely for all and low-/moderate-risk infants. Component selection was described for 8/17 indicators and some form of validation reported for 12/17. Neonatal morbidity prevalence ranged from 4.6% to 9.0% of all infants, 0.4% to 8.0% of low-/moderate-risk infants, and 17.8% to 61.0% of VPT infants. CONCLUSIONS: Multiple neonatal morbidity indicators based on hospital discharge data have been used for research, but their heterogeneity limits comparisons between studies. Standard neonatal outcome measures are needed for benchmarking and synthesis of research results.

Prevalence of and Risk Factors for Anal Oncogenic Human Papillomavirus Infection Among HIV-Infected Women in France in the Combination Antiretroviral Therapy Era.

BACKGROUND: Little is known about the type-specific prevalence of anal human papillomavirus (HPV) infection and risk factors for anal high-risk (HR) HPV infection in human immunodeficiency virus (HIV)-infected women. METHODS: A cross-sectional study of anal and cervical HPV infection was nested within a gynecological cohort of HIV-infected women. Specimens were tested for type-specific DNA using a polymerase chain reaction-based assay. RESULTS: The study population consisted of 311 women with a median age of 45.3 years, of whom 42.8% originated from sub-Saharan Africa and 96.8% were receiving combination antiretroviral therapy. The median CD4(+)cell count was 612/µL, and the HIV load was <50 copies/mL in 84.1%. HR-HPV types were detected in the anal canal in 148 women (47.6%) and in the cervix in 82 (26.4%). HPV-16 was the most prevalent type in both the anal canal (13.2% of women) and the cervix (5.1%). In multivariable analysis, factors associated with prevalent anal HR-HPV infection were CD4(+)count <350/µL (odds ratio, 2.9; 95% confidence interval, 1.3-6.5), concurrent cervical lesions (2.6; 1.0-4.3), and cervical HR-HPV infection (1.8; 1.0-3.2). CONCLUSIONS: The high prevalence of HR-HPV types, including HPV-16, in the anal canal of HIV-positive women is concerning. Anal cancer screening should be considered for HIV-positive women as part of their routine care.

High Prevalence of Anal Human Papillomavirus-Associated Cancer Precursors in a Contemporary Cohort of Asymptomatic HIV-Infected Women.

BACKGROUND: Although human immunodeficiency virus (HIV)-infected women are at high risk for anal cancer, few data have been published on prevalence of and risk factors for anal precancer and potential screening strategies in this risk group. METHODS: A cross-sectional anal screening study was nested in a gynecological cohort of HIV-infected women. Anal swab specimens were collected for cytology and human papillomavirus (HPV) testing. High-resolution anoscopy, with biopsy when indicated, was systematically performed. RESULTS: Among the 171 enrolled women, median age was 47.3 years and 98% were receiving combination antiretroviral therapy. Median CD4(+) count was 655 cells/µL and HIV load was <50 copies/mL in 89% of subjects. High-grade anal intraepithelial neoplasia or worse (HG-AIN+) was diagnosed in 12.9% (n = 21). In multivariable analysis, a history of cervical squamous intraepithelial lesion (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.1-16.4) and anal HPV-16 infection (OR, 16.1; 95% CI, 5.4-48.3) was associated with increased risk of HG-AIN+. Abnormal anal cytology and HPV-16 infection performed best as a screening strategy for HG-AIN+ histology, with positive likelihood ratios of 3.4 (95% CI, 2.3-5.1) and 4.7 (95% CI, 2.5-8.7) and negative likelihood ratios of 0.2 (95% CI, .07-.8) and 0.4 (95% CI, .2-.9), respectively. CONCLUSIONS: HIV-infected women with a history of HPV-associated cervical disease are at increased risk for HG-AIN+ and should be offered anal cancer screening. Anal cytology and HPV-16 genotyping had the best screening performance. Anal cytology is easy to perform routinely; it may be the best candidate for screening for HG-AIN among HIV-infected women.

Risk factors for placenta accreta spectrum disorders in women with any prior cesarean and a placenta previa or low lying: a prospective population-based study.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

Mental health of pregnant women during the SARS-CoV-2 pandemic in France: Evolution of self-perceived psychological state during the first lockdown, and anxiety frequency two months after the lockdown ended.

Previous pandemics and related lockdowns have had a deleterious impact on pregnant women's mental health. We studied the impact of the SARS-CoV-2/Covid-19 pandemic and France's first lockdown on pregnant women's mental health. A cross-sectional study was conducted in July 2020 using a web-questionnaire completed by 500 adult women who were pregnant during the first lockdown in France (March-May 2020). Questions focused on their self-perceived psychological state and affects they felt before and during the lockdown and anxiety symptomatology (HAD) two months after it ended. A robust variance Poisson regression model was used to estimate adjusted prevalence ratios (aPR) for anxiety and self-perceived psychological state evolution. One in five respondents (21.1%) reported psychological deterioration during lockdown. Associated determinants were: i) little or no social support (self-perceived) (aRP = 1.77, 95%CI[1.18-2.66]), ii) increased workload (1.65, [1.02-2.66]), and iii) poor/moderate knowledge about SARS-CoV-2 transmission (1.60, [1.09-2.35]). Seven percent of women reporting psychological deterioration had access to professional psychological support during lockdown, while 19% did not despite wanting it. Women reported heightened powerlessness (60.3%), frustration (64%) and fear (59.2%) during lockdown. One in seven respondents (14.2%, 95%CI[10.9-18.2]) had anxiety symptoms. Determinants associated: i) at least one pregnancy-related pathology (aPR = 1.82, 95%CI[1.15-2.88]), ii) overweightness or obesity (1.61, [1.07-2.43]), iii) one child under the age of six years in the household during the lockdown (3.26, [1.24-8.53]), iv) little or no social support (self-perceived) during the lockdown (1.66, [1.07-2.58]), v) friend or relatives diagnosed with Covid-19 or with symptoms of the disease (1.66; [1.06-2.60]), vi) no access to medication for psychological distress (2.86, [1.74-4.71]), and vii) unsuccessfully seeking exchanges with healthcare professionals about their pregnancy during the pandemic (1.66, [1.08-2.55]). Our results can guide prevention and support policies for pregnant women during pandemics, current or future, with or without lockdowns. Preventing perinatal mental health problems is essential to ensure a supportive environment for the child's development.

Impact of the 1st Wave of the COVID-19 Pandemic and Lockdown on In Utero Transfer Activity in the Paris Area, France.

BACKGROUND: To assess changes in the number and profile of in utero transfer requests during the first lockdown. METHODS: An observational, retrospective, cohort study. All pregnant women, from the Paris area (France), for whom a request for in utero transfer to the transfer unit was made during the first lockdown in France (from 17 March to 10 May 2020) or during a mirror period (years 2016 to 2019) were included. We compared the numbers and proportions of various indications for in utero transfer, the rates of in utero transfer acceptance and the proportion of outborn deliveries. RESULTS: 206 transfer requests were made during the lockdown versus 227, 236, 204 and 228 in 2016, 2017, 2018 and 2019, respectively. The relative proportion of requests for threatened preterm births and for fetal growth restriction decreased from 45% in the mirror period to 37% and from 8 to 3%, respectively. The transfer acceptance rates and outborn deliveries did not differ between time periods. CONCLUSIONS: Although a reduction in in utero transfer requests was observed for certain indications, the first lockdown was not associated with a decrease in acceptance rates nor in an increase in outborn births of pregnancies with a high risk of prematurity in the Paris area.

Does the Quality of Postpartum Hemorrhage Local Protocols Improve the Identification and Management of Blood Loss after Vaginal Deliveries? A Multicenter Cohort Study.

Substandard care, which can result from a delayed recognition of the severity of blood loss, can increase maternal morbidity. Our objectives were to assess the incidence of postpartum hemorrhage (PPH) and of second-line procedures in maternity units according to the quality of their PPH protocol. We used a mixed design, a prospective cohort (3442 women with PPH after vaginal delivery; February−July 2011), and an audit of the written protocols (177 French maternity units; September 2010−June 2011). A quality score was calculated for the protocol of each unit. Maternity units were classified into three categories according to this score: category 1 (total score: 0−8), category 2 (9−12.5), and category 3 (>12.5). The PPH incidence (>500 mL) was 3.2%, 3.3% and 4.6% among maternity units in categories 1, 2 and 3, respectively (p < 0.0001). The incidence of severe maternal morbidity (surgery and/or artery embolization and/or blood transfusion) was higher among maternity units in category 1 (54.8%; 95% CI: 51.9, 57.7) than in either category 2 (50.1%; 95% CI: 47.8, 52.5) or 3 (38.0%; 95% CI: 33.8, 42.4]) (p < 0.0001). The risks of severe maternal morbidity were lower for category 3 than category 1 and 2 (respectively, adjusted RR 0.68, 95% CI 0.60−0.86 and 0.77, 95% CI 0.68−0.87). Finally, maternity units with higher scores identified PPH better and used fewer curative second-line procedures.

Pregnant women's unmet need to communicate with a health professional during the SARS-CoV-2 pandemic lockdown in France: The Covimater cross-sectional study.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic lockdown, communication between pregnant women and health professionals may have become complicated due to restrictions on movement and saturated health services. This could have impacts on pregnancy monitoring and women's wellbeing. We aimed to i) describe the unmet need of pregnant women living in France to communicate with health professionals about the pandemic and their pregnancy during the lockdown, ii) assess the socio-demographic, medical and contextual factors associated with this unmet need. The Covimater cross-sectional study, conducted in July 2020, includes data on 500 adult women's experiences of pregnancy during the first lockdown period in France (i.e., from March to May 2020). The women, all residents in metropolitan France, answered a web-based questionnaire about their conversations with health professionals during the lockdown, as well as their social and medical characteristics. A robust variance Poisson regression model was used to estimate crude or adjusted prevalence ratios (aPRs) for their unmet need to communicate with health professionals about the pandemic and their pregnancy. Forty-one percent of participants reported an unmet need to communicate with a health professional during the lockdown, mainly about the risk of transmitting SARS-CoV-2 to their baby and the consequences for the latter. Factors associated were: i) being professionally inactive (aPR = 1.58,CI95%[(1.14-2.21]), ii) having an educational level below secondary school diploma (1.38,[1.05,-1.81]), iii) having experienced serious arguments/violence (2.12,[1.28-3.52]), iv) being very worried about the pandemic (1.41,[1.11-1.78]), v) being primiparous (1.36,[1.06-1.74]) and vi) having had pregnancy consultations postponed/cancelled by health professionals during the lockdown (1.35,[1.06-1.73]). These results can be used to develop targeted strategies that ensure pregnant women are able to i) communicate with health professionals about the potential impact of the SARS-CoV-2 pandemic on their pregnancy, and ii) access up-to-date and reliable information on the consequences of SARS-CoV-2 for themselves and their child.

Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study).

We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.3. This good penetration of raltegravir may contribute to the control of viral replication in the female genital tract.

Is a planned cesarean necessary in twin pregnancies?

OBJECTIVE: Evaluation of elective cesarean section for twin delivery as a standard of care. DESIGN: Historical cohort in a national database (2 597 twin pregnancies). SETTING: France. SAMPLE: Twins with first child in cephalic presentation. METHODS: Decision analysis. MAIN OUTCOME MEASURES: All neonatal complications, i.e. death, whether intrapartum or in the delivery room or the immediate postpartum period, or neonatal transfer to intensive (or special) care, or trauma, of one or both twins. RESULTS: When we focused on neonatal complications for either or both twins, the strategy of planned vaginal delivery was preferable; the weight of its decision tree branch was lower than that for planned cesarean (26.5 vs. 31.7). If only twin 2 was considered, vaginal delivery was also preferred (weight of vaginal delivery=27.6 vs. 32.7 for planned cesarean). As long as the morbidity and mortality of twin 1 or twin 2 or both during a cesarean for twin 2 in the case of planned vaginal delivery does not exceed 31.5%, all else being equal, vaginal delivery should be preferred to a planned cesarean for twin 1 and twin 2. The two-variable sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The results of our study do not support a policy of planned cesarean delivery for twin pregnancies at and after 34 weeks of gestation. LEVEL OF EVIDENCE: II.

A French audit of maternity unit protocols for immediate postpartum hemorrhage: A cross-sectional study (HERA).

OBJECTIVES: The principal objective of this work was to assess how well the written protocols of maternity units used for the prevention and management of postpartum hemorrhage (PPH) corresponded to the 2004 French guidelines on this topic. The second objective was to assess whether or not this correspondence with the national guidelines varied according to hospital level (basic, specialized, and subspecialized) and status (teaching, public, and private). METHODS: This observational multicenter cross-sectional study took place in September 2010 and included French perinatal networks that volunteered to participate. We asked 300 French maternity units belonging to these networks to participate by emailing a copy of their department's protocol for PPH to the study team. This team designed and performed a clinical audit of these protocols, defining 16 criteria that incorporated the 2004 French guidelines for prevention and management of PPH. The main outcome measure was the percentage of units reporting protocols meeting these criteria. RESULTS: Of the 244 maternity units responding, 97.1 % had a written protocol but only 67.0 % had a local protocol. Protocol correspondence with the 2004 French guidelines was good for the criteria involving quantitative assessment of the quantity of blood loss (83.5 %) and secondary management of PPH (>80 %). Correspondence with the guidelines was poor in terms of defining PPH in the protocol (25.3 %) and of requiring the recording of the time of PPH diagnosis (53.2 %) and of the volume of blood loss (55.7 %). These results differed only slightly according to maternity unit status or level. CONCLUSION: In all, 67.0 % (159/237) of maternity units had a local protocol for PPH. The contents of these protocols should be improved to be closer to the national guidelines.

Is a breech presentation at term more frequent in women with a history of cesarean delivery?

OBJECTIVE: The purpose of this study was to determine whether breech presentation at term is more common among women with at least 1 previous cesarean delivery. STUDY DESIGN: This historic cohort study (n = 84,688) included women with a singleton term pregnancy and at least 1 previous delivery. Results were expressed as crude relative risks and adjusted odds ratios. RESULTS: While 2.46% of women had a fetus in breech presentation at term, 14.91% of women had had 1 or more previous cesareans. The relative risk of a breech presentation at term for women with a history of cesarean was 2.18 (95%CI: 1.98-2.39). It did not differ according to the number of previous cesareans. The logistic regression analysis took into account confounding factors including gestational age, maternal age, parity, birthweight, and oligohydramnios. The adjusted odds ratio was 2.12 (95%CI: 1.91-2.36). CONCLUSION: Women with previous cesarean deliveries have a risk of breech presentation at term twice that of women with previous vaginal deliveries.

Atazanavir in pregnancy: impact on neonatal hyperbilirubinemia.

OBJECTIVE: To study the impact on the neonate of maternal antiretroviral therapy with atazanavir (ATV). STUDY DESIGN: An observational study of 22 HIV-infected women receiving, for clinical indications, antiretroviral therapy with ATV 300 mg and ritonavir 100mg during pregnancy and their 23 HIV infants (including a twin pair). RESULTS: Mothers had received ATV for a median duration of 19 months [range 3-49] by delivery. At delivery, plasma HIV-RNA was <40 copies/mL in all patients. Liver enzymes were normal in 19/22 patients, but one woman had grade 3-4 liver toxicity. Maternal serum bilirubin concentrations were above the upper limit of normal in most patients, with grade 3 toxicity in 5 patients. All but one woman had trough ATV concentrations during pregnancy above the minimum effective concentration. The median cord blood ATV concentration was 130 ng/mL [range<30-758]; the cord/maternal ratio was 21%. All neonates were born at term [median 38.2 weeks]. Three neonates had mildly elevated AST transaminase levels. Bilirubin concentrations at birth were significantly higher than maternal concentrations, with a median of 44 µm/L [range 24-129]; values on days 2-3 were 63 [8-212]. Five neonates had jaundice requiring phototherapy, without liver damage, and recovered without sequelae. CONCLUSION: Neonates whose mothers were treated with ATV should be monitored for hyperbilirubinemia, which may be due to placental transfer of unconjugated bilirubin from the mother and/or a direct effect of transplacental ATV on bilirubin metabolism in the fetus.