Emerging and re-emerging infectious diseases in pregnant women in an amazonian region: a large retrospective study from French Guiana.

PURPOSE: Over the past decade, the Amazon basin has faced numerous infectious epidemics. Our comprehension of the actual extent of these infections during pregnancy remains limited. This study aimed to clarify the clinical and epidemiological features of emerging and re-emerging infectious diseases during pregnancy in western French Guiana and along the Maroni River over the previous nine years. METHODS: This retrospective cohort study enrolled pregnant women living in west French Guiana territory and giving birth in the only local referral center after 22 weeks of gestation between 2013 and 2021. Data on symptomatic or asymptomatic biologically confirmed emerging or re-emerging diseases during pregnancy was collected. RESULTS: Six epidemic waves were experienced during the study period, including 498 confirmed Zika virus infections (2016), 363 SARS-CoV-2 infections (2020-2021), 87 chikungunya virus infections (2014), 76 syphilis infections (2013-2021), and 60 dengue virus infections (2013-2021) at different gestational ages. Furthermore, 1.1% (n = 287) and 1.4% (n = 350) of pregnant women in west French Guiana were living with HIV and HTLV, respectively. During the study period, at least 5.5% (n = 1,371) faced an emerging or re-emerging infection during pregnancy. CONCLUSION: These results highlight the diversity, abundance, and dynamism of emerging and re-emerging infectious agents faced by pregnant women in the Amazon basin. Considering the maternal and neonatal adverse outcomes associated with these infections, increased efforts are required to enhance diagnosis, reporting, and treatment of these conditions.

Maternal and neonatal outcomes of French prospective multicenter cohort study COVIPREG during the first two COVID-19 waves.

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).

[Prevention of Rh D Alloimmunization in the first trimester of the pregnancy: French College of Obstetricians and Gynecologists guidelines for clinical practice.] / Prévention de l'allo-immunisation anti-RH1 au premier trimestre de la grossesse: recommandations pour la pratique clinique du Collège National des Gynécologues-Obstétriciens Français.

OBJECTIVE: To provide recommendations for the prevention of Rh D alloimmunization in the first trimester of pregnancy. MATERIALS AND METHODS: The quality of evidence of the literature was assessed following the GRADE methodology with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on Pubmed, Cochrane, EMBASE, and Google Scholar databases. The quality of evidence was assessed (high, moderate, low, very low) and a recommendation was formulated: (i) strong, (ii) weak, or (iii) no recommendation. The recommendations were reviewed in two rounds with reviewers from the scientific board of the French College of the OB/GYN (Delphi survey) to select the consensus recommendations. RESULTS: The three recommendations from PICO questions reached agreement using the Delphi method. It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in case of abortion or miscarriage, in RhD negative patients when the genitor is RhD positive or unknown (Weak recommendation. Very low-quality evidence). It is recommended not to administer Rh D immunoglobulin before 12 weeks of gestation to reduce the risk of alloimmunization in cases of bleeding in an ongoing intrauterine pregnancy (Weak recommendation. Very low-quality evidence). The literature data are insufficient in quality and quantity to determine if the injection of Rh D immunoglobulin reduces the risk of alloimmunization in the case of an ectopic pregnancy (No recommendation. Very low-quality evidence). CONCLUSION: Even though the quality of evidence from the studies is very low, it is recommended not to administer Rh D immunoglobulin in case of abortion, miscarriage or bleeding before 12 weeks of amenorrhea. The quality of evidence was too low to issue a recommendation regarding ectopic pregnancy.

Impact of an e-learning training for interpreting intrapartum fetal heart rate monitoring to avoid perinatal asphyxia: A before-after multicenter observational study.

INTRODUCTION: Perinatal asphyxia, a condition that results from compromised placental or pulmonary gas exchange during the birth process, is rare but can lead to serious neonatal and long-term consequences. The visual analysis of cardiotocography (CTG) is designed to avoid perinatal asphyxia, but its interpretation can be difficult. Our aim was to test the impact of an e-learning training program for interpreting CTG on the rate of avoidable perinatal asphyxia at term. METHOD: We conducted a retrospective multicenter before-after study comparing two periods, before and after the implementation of e-learning training program from July 1, 2016 to December 31, 2016, in CTG interpretation for midwives and obstetricians in five maternity hospitals in the Paris area, France. The training involved theoretical aspects such as fetal physiology and heart rhythm abnormalities, followed by practical exercises using real case studies to enhance skills in interpreting CTG. We included all term births that occurred between the "before" period (July 1 to December 31, 2014) and the "after period (January 1 to June 30, 2017). We excluded multiple pregnancies, antenatal detection of congenital abnormalities, breech births and all scheduled caesarean sections. Perinatal asphyxia cases were analyzed by a pair of experts consisting of midwives and obstetricians, and avoidability of perinatal asphyxia was estimated. The main criterion was the prevalence of avoidable perinatal asphyxia. RESULTS: The e-learning program was performed by 83 % of the obstetrician-gynecologists and 65 % of the midwives working in the delivery rooms of the five centers. The prevalence of perinatal asphyxia was 0.45 % (29/7902 births) before the training and 0.54 % (35/7722) after. The rate of perinatal asphyxia rated as avoidable was 0.30 % of live births before the training and 0.28 % after (p = 0.870). The main causes of perinatal asphyxia deemed avoidable were delay in reactions to severe CTG anomalies and errors in the analysis and interpretation of the CTG. These causes did not differ between the two periods. CONCLUSION: One session of e-learning training to analyze CTG was not associated with a reduction in avoidable perinatal asphyxia. Other types of e-learning, repeated and implemented over a longer period should be evaluated.

Trends in harmful drug exposure during pregnancy in France between 2013 and 2019: A nationwide cohort study.

OBJECTIVE: Describe the trends of exposure to harmful drugs during pregnancy over recent years in France. DESIGN: Nationwide cohort study. SETTING: The French National administrative health Data System (SNDS). POPULATION: Pregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths. METHODS: Each pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs. MAIN OUTCOME MEASURES: Prevalence of pregnancies exposed to at least one harmful drug. RESULTS: Among 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids. CONCLUSIONS: In this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.

[Preeclampsia: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies to reduce maternal and neonatal morbidity related to preeclampsia. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and recommendations were formulated as a (i) strong, (ii) weak or (iii) no recommendation. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Preeclampsia is defined by the association of gestational hypertension (systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg) and proteinuria≥0.3g/24h or a Proteinuria/Creatininuria ratio≥30mg/mmol occurring after 20 weeks of gestation. Data from the literature do not show any benefit in terms of maternal or perinatal health from implementing a broader definition of preeclampsia. Of the 31 questions, there was agreement between the working group and the external reviewers on 31 (100%). In general population, physical activity during pregnancy should be encouraged to reduce the risk of preeclampsia (Strong recommendation, Quality of the evidence low) but an early screening based on algorithms (Weak recommendation, Quality of the evidence low) or aspirin administration (Weak recommendation, Quality of the evidence very low) is not recommended to reduce maternal and neonatal morbidity related to preeclampsia. In women with preexisting diabetes or hypertension or renal disease, or multiple pregnancy, the level of evidence is insufficient to determine whether aspirin administration during pregnancy is useful to reduce maternal and perinatal morbidity (No recommendation, Quality of the evidence low). In women with a history of vasculo-placental disease, low dose of aspirin (Strong recommendation, Quality of the evidence moderate) at a dosage of 100-160mg per day (Weak recommendation, Quality of the evidence low), ideally before 16 weeks of gestation and not after 20 weeks of gestation (Strong recommendation, Quality of the evidence low) until 36 weeks of gestation (Weak recommendation, Quality of the evidence very low) is recommended. In a high-risk population, additional administration of low molecular weight heparin is not recommended (Weak recommendation, Quality of the evidence moderate). In case of preeclampsia (Weak recommendation, Quality of the evidence low) or suspicion of preeclampsia (Weak recommendation, Quality of the evidence moderate, the assessment of PlGF concentration or sFLT-1/PlGF ratio is not routinely recommended) in the only goal to reduce maternal or perinatal morbidity. In women with non-severe preeclampsia antihypertensive agent should be administered orally when the systolic blood pressure is measured between 140 and 159mmHg or diastolic blood pressure is measured between 90 and 109mmHg (Weak recommendation, Quality of the evidence low). In women with non-severe preeclampsia, delivery between 34 and 36+6 weeks of gestation reduces severe maternal hypertension but increases the incidence of moderate prematurity. Taking into account the benefit/risk balance for the mother and the child, it is recommended not to systematically induce birth in women with non-severe preeclampsia between 34 and 36+6 weeks of gestation (Strong recommendation, Quality of evidence high). In women with non-severe preeclampsia diagnosed between 37+0 and 41 weeks of gestation, it is recommended to induce birth to reduce maternal morbidity (Strong recommendation, Low quality of evidence), and to perform a trial of labor in the absence of contraindication (Strong recommendation, Very low quality of evidence). In women with a history of preeclampsia, screening maternal thrombophilia is not recommended (Strong recommendation, Quality of the evidence moderate). Because women with a history of a preeclampsia have an increased lifelong risk of chronic hypertension and cardiovascular complications, they should be informed of the need for medical follow-up to monitor blood pressure and to manage other possible cardiovascular risk factors (Strong recommendation, Quality of the evidence moderate). CONCLUSION: The purpose of these recommendations was to reassess the definition of preeclampsia, and to determine the strategies to reduce maternal and perinatal morbidity related to preeclampsia, during pregnancy but also after childbirth. They aim to help health professionals in their daily clinical practice to inform or care for patients who have had or have preeclampsia. Synthetic information documents are also offered for professionals and patients.

Twice-daily versus once-daily vaginal dinoprostone gel for induction of labor at term: A randomized controlled trial.

OBJECTIVE: The aim of this study was to compare twice-daily versus once-daily administration of intravaginal PGE2 for induction of labor at term. Efficacy, safety, and patient satisfaction were evaluated. STUDY DESIGN: For this single-center, randomized, comparative, open-label, two-arm, and parallel study, pregnant women with term singleton live pregnancies ≥ 37 weeks of gestation, medical indications for induction of labor, and Bishop score ≤ 6 were randomized to either the control group (induction of labor with PGE2 gel with repeat dose after 24 h) or the experimental group (repeat dose after 12 h). The primary outcome was induction-to-delivery interval time. Secondary outcomes were maternal and neonatal outcomes and patient satisfaction. RESULTS: In total, 246 women were randomized to the control (n = 121) or experimental groups (n = 125). The mean time for initiation of induction to delivery was 9.4 h shorter in the experimental group compared to controls (p = 0.007). For control vs experimental, there were no differences in tachysystole (19/121, 15.7 % vs 21/124, 16.9 %, respectively; p = 0.79), cesarean section rate (18/121, 14.9 % vs 28/124, 22.6 % respectively; p = 0.12), or other main obstetrical or neonatal outcomes. Patients in the experimental group reported higher satisfaction with their induction (48/96, 50 % with once-daily vs 60/86, 69.8 % with twice-daily; p = 0.010). CONCLUSION: Among women admitted for induction of labor at term, closer interval of vaginal PGE2 administration was associated with a significantly shorter induction-to-delivery time without increasing maternal or neonatal morbidity. Furthermore, the reduction in induction time was associated with improved patient experience of delivery.

Prevalence and associated factors of antibiotic exposure during pregnancy in a large French population-based study during the 2010-19 period.

BACKGROUND: Although bacterial infections are frequent during pregnancy, the prescription of antibiotics to pregnant women represents a challenge for physicians, driven by the benefit-risk balance. OBJECTIVES: To assess the extent of prenatal antibiotic exposure and its associated factors. METHODS: This study included pregnancies in the National Mother-Child EPI-MERES Register 2010-19 (built from the French Healthcare Data System) regardless of outcome. Antibiotic exposure was defined as having at least one antibiotic prescription filled during pregnancy. The prevalence of pregnancies exposed to antibiotics was estimated. Univariable Poisson regression with generalized estimating equations was used to compare the number of antibiotic prescriptions filled during pregnancy and the period after pregnancy with the period 1 year before pregnancy. Multivariable Poisson regression was used to investigate factors associated with antibiotic exposure during pregnancy. RESULTS: Among 9 769 764 pregnancies, 3 501 294 (35.8%) were exposed to antibiotics and amoxicillin was the most common. Compared with a similar period 1 year before pregnancy, the number of filled antibiotic prescriptions was lower during pregnancy [incidence rate ratio (IRR) 0.903 (95% CI 0.902-0.905)] and during the period 1 year after pregnancy [IRR 0.880 (95% CI 0.879-0.881)]. Region of residence, deprivation index, smoking-related conditions and chronic diseases (especially chronic respiratory diseases) were associated with antibiotic exposure during pregnancy. CONCLUSIONS: Antibiotic prescriptions are filled less frequently during pregnancy than during the preceding year. This may be due to a more relevant benefit-risk assessment. Pregnant women living with social deprivation, those with smoking-related conditions and those with chronic diseases are more likely to fill antibiotic prescriptions.

Impact of prenatal corticosteroid therapy on sickle cell disease in pregnant women.

OBJECTIVE: To evaluate safety of prenatal corticosteroids in pregnancies of women with sickle cell disease. METHODS: A multicenter observational study of patients with sickle cell disease, comparing vaso-occlusive crises (VOC) requiring hospital care between pregnancies with versus without prenatal corticosteroids. RESULTS: In 40 pregnancies exposed to prenatal corticosteroids, compared with 370 unexposed pregnancies, VOC were not more frequent (62.5% vs 57.9%, P = 0.578) but they were more severe, with more intensive care hospitalizations (25.0% vs 12.9%, P = 0.039), emergency transfusions (44.7% vs 22.7%, P = 0.006), and acute chest syndromes (22.5% vs 8.9%, P = 0.010). These differences persisted after adjustment for severity and type of sickle cell syndrome (for intensive care admission adjusted odds ratio [aOR] 2.73, 95% confidence interval [CI] 1.10-6.79, P = 0.031 and for acute chest syndrome aOR 4.15, 95% CI 1.57-14.4, P = 0.008). VOC occurred on average 1.2 days following steroid administration. When comparing 36 patients receiving corticosteroids for fetal maturation with 58 patients who were hospitalized for obstetrical complications before 34 weeks of pregnancy but that did not receive corticosteroids, VOC incidence was not significantly higher (41.7% vs 31.5%, P = 0.323). CONCLUSION: The present study was the first to study the impact of prenatal corticosteroids on sickle cell disease. They were associated with more severe VOC, suggesting that steroids should be avoided in these women.

Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study.

OBJECTIVES: Because NRTIs can have fetal toxicities, we evaluated a perinatal NRTI-sparing strategy to prevent perinatal HIV transmission. Our primary objective was to determine the proportion maintaining a viral load (VL) of <50 copies/mL up to delivery on darunavir/ritonavir monotherapy, without requiring treatment intensification. METHODS: In a one-arm, multicentre Phase 2 clinical trial, eligible patients in the first trimester of pregnancy on ART with plasma VL < 50 copies/mL received maintenance monotherapy with darunavir/ritonavir, 600/100 mg twice daily. VL was monitored monthly. ART was intensified in the case of VL > 50 copies/mL. Neonates received nevirapine prophylaxis for 14 days. RESULTS: Of 89 patients switching to darunavir/ritonavir monotherapy, 4 miscarried before 22 weeks' gestation, 2 changed treatment for elevated liver enzymes without virological failure, and 83 were evaluable for the main outcome. Six had virological failure confirmed on a repeat sample (median VL = 193 copies/mL; range 78-644), including two before switching to monotherapy. In these six cases, ART was intensified with tenofovir disoproxil fumarate/emtricitabine. The success rate was 75/83, 90.4% (95% CI, 81.9%-95.7%) considering two patients with VL missing at delivery as failures, and 77/83, 92.8% (95% CI, 84.9%-97.3%) when considering them as successes since both had undetectable VL on darunavir/ritonavir throughout pregnancy. In ITT, the last available VL before delivery was <50 copies/mL in all of the patients. There was no case of perinatal HIV transmission. CONCLUSIONS: Darunavir/ritonavir maintenance monotherapy required intensification in nearly 10% of cases. This limits its widespread use, thus other regimens should be evaluated in order to limit exposure to antiretrovirals, particularly NRTIs, during pregnancy.

Impact of SARS-CoV-2 Infection on Unvaccinated Pregnant Women: Non-Reassuring Fetal Heart Rate Tracing Because of Placentitis.

In 2020, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. SARS-CoV-2 infection has been shown to be highly morbid in pregnant women, being a risk factor for several obstetric conditions leading to increased maternal and neonatal mortality. A few studies since 2020 have shown SARS-CoV-2 maternal-fetal transmission and noted placental abnormalities grouped under the term placentitis. We hypothesized that these placental lesions could be responsible for abnormalities in placental exchange and therefore abnormalities in cardiotocographic monitoring, leading to premature fetal extraction. The objective is to identify the clinical, biochemical, and histological determinants associated with the occurrence of non-reassuring fetal heart rate (NRFHR) outside labor in fetuses of SARS-CoV-2-infected mothers. We conducted a retrospective multicenter case series of the natural history of maternal SARS-CoV-2 infections resulting in fetal delivery outside labor due to NRFHR. Collaboration was sought with the maternity hospitals in the CEGORIF, the APHP and Brussels hospitals. The investigators were contacted by e-mail on three successive occasions over a period of one year. Data from 17 mothers and 17 fetuses were analyzed. Most women had a mild SARS-CoV-2 infection; only two women presented severe infection. No woman was vaccinated. We found a substantial proportion of maternal coagulopathy at birth: elevation of APTT ratio (62%), thrombocytopenia (41%) and liver cytolysis (58.3%). Iatrogenic prematurity was noted in 15 of 17 fetuses, and 100% were born by cesarean delivery due to emergency criteria. One male neonate died on the day of birth due to peripartum asphyxia. Three cases of maternal-fetal transmission were recorded following WHO criteria. Placental analysis in 15 cases revealed eight cases of SARS-CoV-2 placentitis, causing placental insufficiency. In total, 100% of the placentas analyzed showed at least one lesion suggestive of placentitis. SARS-CoV-2 maternal infection during pregnancy is likely to generate neonatal morbidity in relation to placental damage resulting in placental insufficiency. This morbidity may be the consequence of induced prematurity as well as acidosis in the most severe situations. Placental damage occurred in unvaccinated women and in women with no identified risk factor, in contrast to severe maternal clinical forms.

Failed induction of labor in term nulliparous women with an unfavorable cervix: Comparison of cervical ripening by two forms of vaginal prostaglandins (slow-release pessary and vaginal gel).

OBJECTIVE: To compare the rate of failed induction after cervical ripening by two forms of vaginal prostaglandins. MATERIAL AND METHODS: This two-year retrospective study (January 1, 2016, through December 31, 2017) in two tertiary maternity units included nulliparous women with a singleton fetus in cephalic presentation and an unfavorable cervix requiring labor induction for prolonged pregnancy. The principal endpoint was the rate of failed induction, defined by the performance of a cesarean delivery before 6 cm of dilation. Cervical ripening was initiated by prostaglandins for 24 h, using a slow-release pessary (unit A) or a vaginal gel (unit B). The care protocol of the two groups after the first 24 h were similar. The women's individual characteristics were compared between the two units. The rates of failed induction were then compared between the two units, first by univariate and then by multivariable analysis adjusted for the characteristics that differed significantly between the units. RESULTS: Among the 17,217 women delivered in the two maternity units during the study period, 178 met our inclusion criteria (125 in unit A (slow-release pessary) and 53 in unit B (vaginal gel)). The rate of failed induction was similar: 21.6% in unit A (slow-release pessary) and 17.0% in unit B (vaginal gel) (P = 0.48). The multivariate analysis did not show any difference about failed induction, time from the onset of induction to delivery, and vaginal delivery rate within 24h. CONCLUSION: The rate of failed induction of labor did not differ between slow-release pessary and vaginal gel.

Brief Report: T-Cell Receptor α Repertoire Diversity at Birth After in utero Exposure to HIV Integrase Strand-Transfer Inhibitors.

ABSTRACT: Effectiveness of anti-HIV in the prevention of perinatal transmission has been established. Assessing the tolerance of drug exposure during pregnancy is of the utmost importance given the number of children exposed. HIV integrase and the recombinase-activating gene enzyme involved in the establishment of the T-lymphocyte repertoire show structural similarity. The inhibition of recombinase-activating (RAG) gene by anti-integrases is observed in vitro, in a variable way according to the molecules. Here, we show that in utero exposure to raltegravir did not alter the T-lymphocyte repertoire of 12 newborns. These reassuring data merit verification for other anti-integrases. ( ClinicalTrial.org NCT04024150).

Update of Perinatal Human Immunodeficiency Virus Type 1 Transmission in France: Zero Transmission for 5482 Mothers on Continuous Antiretroviral Therapy From Conception and With Undetectable Viral Load at Delivery.

BACKGROUND: Antiretroviral therapy (ART) is remarkably effective in preventing perinatal transmission (PT) of HIV-1. We evaluated the PT rate in a population of women with widespread access to ART before conception. METHODS: The analysis included 14 630 women with HIV-1 who delivered from 2000 to 2017 at centers participating in the nationwide prospective multicenter French Perinatal Cohort (ANRS-EPF). PT was analyzed according to time period, timing of ART initiation, maternal plasma viral load (pVL), and gestational age at birth. No infants were breastfed, and all received neonatal prophylaxis. RESULTS: PT decreased between 3 periods, from 1.1% in 2000-2005 (58/5123) to 0.7% in 2006-2010 (30/4600) and to 0.2% in 2011-2017 (10/4907; P < .001). Restriction of the analysis to the 6316/14 630 (43%) women on ART at conception, PT decreased from 0.42% (6/1434) in 2000-2005 to 0.03% (1/3117) in 2011-2017 (P = .007). Among women treated at conception, if maternal pVL was undetectable near delivery, no PT was observed regardless of the ART combination [95%CI 0-0.07] (0/5482). Among women who started ART during pregnancy and with undetectable pVL near delivery, PT was 0.57% [95%CI 0.37-0.83] (26/4596). Among women treated at conception but with a detectable pVL near delivery, PT was 1.08% [95%CI 0.49-2.04] (9/834). We also qualitatively described 10 cases of transmission that occurred during the 2011-2017 period. CONCLUSIONS: In a setting with free access to ART, monthly pVL assessment, infant ART prophylaxis, and in the absence of breastfeeding, suppressive ART initiated before pregnancy and continued throughout pregnancy can reduce PT of HIV to almost zero.

Trends in anti-infective use during pregnancy in France between 2010 and 2019: a nationwide population-based study.

AIMS: To describe the trends in anti-infective use during pregnancy between 2010 and 2019 and determine whether they were prescribed according to drug foetal safety international classification systems. METHODS: We conducted a population-based, nationwide study using the French national health data system including all pregnancies ended between 2010 and 2019. Anti-infective agents were considered according to their pharmacological group and potential harmful risk using the Australian and Swedish classification systems. Prevalence rate was estimated annually and by trimester. Average annual percent change (AAPC) and 95% confidence intervals (CIs) were calculated using Joinpoint regression. RESULTS: Among 7 571 035 pregnancies, 3 027 031 (40.0%) received ≥1 antibacterial. This proportion decreased significantly from 41.5% in 2010 to 36.1% in 2019 (AAPC = -1.7%, [95%CI, -2.5 to -1.0%]). Conversely, use of antiviral agents increased during the 10-year study period for anti-herpes simplex virus agents (AAPC = 4.4%, [3.7-5.2%]), influenza agents (AAPC = 25.4%, [6.2-48.1%]) and for HIV-antiretroviral agents (AAPC = 1.3%, [0.6-2.0%]). Use of influenza vaccine increased from 0.2% in 2010 to 4.2% in 2019 (AAPC = 49.7%, [39.3-60.9%]). Among all pregnancies, 0.9% had been exposed to a potentially harmful anti-infective agent increasing from 0.7% in 2010 to 1.2% in 2019 (AAPC = 6.4%, [4.4-8.5%]). CONCLUSION: Based on >7 million pregnancies identified from French nationwide data, this study showed that antibacterials are frequently prescribed during pregnancy although their use has decreased over the past 10 years. Our results suggest that anti-infective agents are generally prescribed in accordance with recommendations, although with a potential for improvement in influenza vaccination.

Guidelines for the management of urgent obstetric situations in emergency medicine, 2022.

OBJECTIVE: To provide recommendations on the management of urgent obstetrical emergencies outside the maternity ward. DESIGN: A group of 24 experts from the French Society of Emergency Medicine (SFMU), the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French College of Gynaecologists and Obstetricians (CNGOF) was convened. Potential conflicts of interest were formally declared at the outset of the guideline development process, which was conducted independently of industry funding. The authors followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the level of evidence in the literature. The potential drawbacks of strong recommendations in the presence of low-level evidence were highlighted. Some recommendations with an insufficient level of evidence were not graded. METHODS: Eight areas were defined: imminent delivery, postpartum haemorrhage (prevention and management), threat of premature delivery, hypertensive disorders in pregnancy, trauma, imaging, cardiopulmonary arrest, and emergency obstetric training. For each field, the expert panel formulated questions according to the PICO model (population, intervention, comparison, outcomes) and an extensive literature search was conducted. Analysis of the literature and formulation of recommendations were conducted according to the GRADE method. RESULTS: Fifteen recommendations on the management of obstetrical emergencies were issued by the SFMU/SFAR/CNGOF panel of experts, and 4 recommendations from formalised expert recommendations (RFE) established by the same societies were taken up to answer 4 PICO questions dealing with the pre-hospital context. After two rounds of voting and several amendments, strong agreement was reached for all the recommendations. For two questions (cardiopulmonary arrest and inter-hospital transfer), no recommendation could be made. CONCLUSIONS: There was significant agreement among the experts on strong recommendations to improve practice in the management of urgent obstetric complications in emergency medicine.

Alternative to intensive management of the active phase of the second stage of labor: a multicenter randomized trial (Phase Active du Second STade trial) among nulliparous women with an epidural.

BACKGROUND: There is no consensus on an optimal strategy for managing the active phase of the second stage of labor. Intensive pushing could not only reduce pushing duration, but also increase abnormal fetal heart rate because of cord compression and reduced placental perfusion and oxygenation resulting from the combination of uterine contractions and maternal expulsive forces. Therefore, it may increase the risk of neonatal acidosis and the need for operative vaginal delivery. OBJECTIVE: This study aimed to assess the effect of the management encouraging "moderate" pushing vs "intensive" pushing on neonatal morbidity. STUDY DESIGN: This study was a multicenter randomized controlled trial, including nulliparas in the second stage of labor with an epidural and a singleton cephalic fetus at term and with a normal fetal heart rate. Of note, 2 groups were defined: (1) the moderate pushing group, in which women had no time limit on pushing, pushed only twice during each contraction, and observed regular periods without pushing, and (2) the intensive pushing group, in which women pushed 3 times during each contraction and the midwife called an obstetrician after 30 minutes of pushing to discuss operative delivery (standard care). The primary outcome was a composite neonatal morbidity criterion, including umbilical arterial pH of <7.15, base excess of >10 mmol/L, lactate levels of >6 mmol/L, 5-minute Apgar score of <7, and severe neonatal trauma. The secondary outcomes were mode of delivery, episiotomy, obstetrical anal sphincter injuries, postpartum hemorrhage, and maternal satisfaction. RESULTS: The study included 1710 nulliparous women. The neonatal morbidity rate was 18.9% in the moderate pushing group and 20.6% in the intensive pushing group (P=.38). Pushing duration was longer in the moderate group than in the intensive group (38.8±26.4 vs 28.6±17.0 minutes; P<.001), and its rate of operative delivery was 21.1% in the moderate group compared with 24.8% in the intensive group (P=.08). The episiotomy rate was significantly lower in the moderate pushing group than in the intensive pushing group (13.5% vs 17.8%; P=.02). We found no significant difference for obstetrical anal sphincter injuries, postpartum hemorrhage, or maternal satisfaction. CONCLUSION: Moderate pushing has no effect on neonatal morbidity, but it may nonetheless have benefits, as it was associated with a lower episiotomy rate.

Congenital lymphocytic choriomeningitis virus: A review.

INTRODUCTION: Lymphocytic choriomeningitis virus (LCMV) uses rodents such as mice and hamsters as its principal reservoir. When women acquire LCMV during pregnancy because of contact with rodents, it can lead to congenital LCMV infection, which is associated with high mortality and morbidity. Although the number of cases reported in the literature is increasing, LCMV is rarely mentioned because a history of exposure to rodents is uncommon and mostly unknown. OBJECTIVES: The main objective of this article was to summarize all morphological, antenatal, and postnatal abnormalities that may suggest a congenital LCMV infection. METHODS: We reviewed PubMed case reports and case series where an antenatal and/or a postnatal description of at least one case of congenital LCMV infection was documented. RESULTS: We found 70 cases of congenital LCMV infection, 68 of which had antenatal or postnatal brain abnormalities, which were mainly chorioretinitis (59/70), hydrocephaly (37/70), microcephaly (22/70), ventriculomegaly (11/70) and periventricular calcifications (11/70). Antenatal and postnatal extracerebral abnormalities were mainly small for gestational age, ascites, cardiomegaly or anemia. Other organ damage was rare, but could include skin abnormalities, hydrops or hepatosplenomegaly. Seventy percent (49/70) of cases had major cerebral abnormalities that could have been detected by antenatal ultrasound examination. Congenital LCMV infection is associated with a significant mortality rate (30%) and survivors often have severe neurologic sequelae. CONCLUSION: LCMV is a rare congenital infection, but awareness of the various prenatal ultrasound morphological abnormalities should be improved, and LCMV should be considered when first-line etiological explorations are negative, especially when the mother's medical history indicates exposure to rodents.

Fetal and neonatal abnormalities due to congenital syphilis: A literature review.

OBJECTIVE: The recent recrudescence of syphilis among women of childbearing age is associated with an increasing number of cases of congenital syphilis. We aimed to summarize the fetal and neonatal abnormalities due to congenital syphilis infection, particularly signs amenable to prenatal diagnosis. METHODS: Eligible studies were retrieved from the PubMed collection database. Articles focusing on postnatal and antenatal abnormalities covered the periods from 1969 to 2019 and 1975-2019, respectively. This review included cohort studies, case series and case reports reporting findings regarding congenital syphilis infections described before and/or after birth. Articles were reviewed by three experts in prenatal diagnosis, and all findings were classified as amenable or not amenable to prenatal diagnosis. RESULTS: A total of 432 cases of congenital syphilis infection were reported. Abnormalities were described antenatally in 161 cases, postnatally in 319 cases, and in both the antenatal and postnatal periods in 57 cases. The most frequently reported signs amenable to prenatal diagnosis were abdominal abnormalities (hepatomegaly, splenomegaly, and bowel abnormalities), fetal growth restriction, and elevated middle cerebral artery peak systolic velocity in the context of ascites or atypical hydrops. Brain abnormalities were rare and never isolated. In the neonatal period, the most common abnormalities were hepatosplenomegaly, bone damage and skin lesions. CONCLUSION: We found that no individual sonographic sign or pattern of signs is pathognomonic for fetal syphilis. In fetuses with ultrasound abnormalities suggestive of congenital infection, syphilis must be considered as part of the work-up.