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).

Sickle cell disease and pregnancy.

Pregnancy is a particularly risky period in the life of patients with sickle cell disease (SCD). Physiological changes during pregnancy increase the risk of vaso-occlusive crises (VOC), acute chest syndrome, venous thromboembolic events, and infections. This concerns haemoglobin (Hb) S/C and S/ß+-thalassaemia patients as much than S/S or S/ß0-thalassaemia patients. SCD also increases the risk of obstetrical complications, such as preeclampsia, in utero foetal death, preterm delivery mostly induced, and intrauterine growth restriction. Thus, pregnancy should be planned and closely monitored by a multidisciplinary team involving obstetricians and sickle cell disease specialists. Before pregnancy, the parents should also be informed about the risk of transmission of this autosomal recessive disease, and the father should therefore be prescribed haemoglobin electrophoresis. Treatments have to be revised when planning pregnancy: hydroxyurea (HU) should be stopped as soon as pregnancy is suspected or confirmed. Preventive blood transfusion is not systematic, but is recommended in the case of a pre-existing transfusion program prior to pregnancy, severe pre-existing organ damage, severe obstetric history, and severe or repeated crises during follow-up, especially in patients taking HU before. Despite the risks of prematurity, systematic administration of corticosteroids for foetal lung maturation is not recommended due to the risk of maternal vaso-occlusive event. Although more frequent, due to obstetrical and maternal complications, caesarean section is not systematic, in the absence of maternal contraindications. It is advisable not to exceed the term of 39 weeks of amenorrhoea. Post-partum follow-up is recommended, particularly because of the risk of thromboembolism.

Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial.

BACKGROUND: Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. METHODS: STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091. FINDINGS: Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population. INTERPRETATION: Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin. FUNDING: French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.

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.

Non-Hemorrhagic Adrenal Infarction during Pregnancy: The Diagnostic Imaging Keys.

Background: non-hemorrhagic adrenal infarction (NHAI) is a rare cause of acute abdominal/flank pain during pregnancy; in order to ensure prompt and appropriate treatment, this diagnosis should not be overlooked. This case series highlights pertinent imaging findings, including ultrasounds (USs), computed tomography (CT), and magnetic resonance imaging (MRI) of recent NHAI cases. Methods: we compiled all consecutive NHAI cases from two university hospitals over a two-year period and checked the relevant clinical, laboratory, and imaging findings. Relevant articles on NHAI published from January 2010 to March 2021 were analyzed. Results: six cases were found in our database. CT-scans typically showed enlarged, hypodense, and non-enhanced adrenal glands. Unenhanced MRIs allowed for diagnoses and showed enlarged adrenal glands in the signal hyperintensity on T2 and diffusion-weighted imaging, without any signal hyperintensity on T1. In two of our six cases, USs showed swollen adrenal glands with fluid collection. Conclusion: NHAI and its differential diagnosis-in cases of acute pain during pregnancy-highlight the crucial roles of integrated radiological examination and cooperation between obstetricians and radiologists, both of whom should consider the location of the pain, the accessibility and tolerance of MRI, and the radiation exposure of CT. Despite its supposed poor sensitivity, an US performed because the patient reports pain should also be used to examine the adrenal gland regions. Non-enhanced MRI is clearly of value and access to it in emergencies is important to avoid radiation exposure.

Impact of simulation-based prenatal invasive procedure training on professional practice, a preliminary study.

INTRODUCTION: Amniocentesis and chorionic villus sampling remain the cornerstone of prenatal diagnosis. These procedures are associated with a risk of miscarriage estimated at approximately 0.5 %. Our team has developed a training model for performing simulation-based prenatal invasive procedures. Several simulation sessions are offered each year to obstetricians-gynecologists involved in fetal medicine in France and abroad. This simulation-based learning has already been conclusively evaluated according to levels I and II of the Kirkpatrick model. Here, we carried out a preliminary study according to level III: does participation in training in prenatal invasive procedures through simulation have an influence on professional practice? METHODS: An anonymous online survey was sent to 82 obstetricians-gynecologists who participated in the training in prenatal invasive procedures at the Antoine Béclère maternity hospital between January 1st, 2014 and December 31, 2018. This questionnaire, entitled "Evaluation of the professional impact of training in invasive procedures through simulation", included 20 quantitative and qualitative items. RESULTS: 48 (59 %) obstetricians-gynecologists responded to the questionnaire. 98 % of the participants considered that participation in the training had a significant impact on their professional practice. Half considered this impact to be major. 60 % of the former participants are now attached to a Multidisciplinary Center for Prenatal Diagnosis. CONCLUSION: Participation in training is considered by former participants to have a significant impact on their professional practice. In order to finalize the evaluation of this learning, a study of the benefits for patients and their pregnancy should be discussed.

SARS-COV-2 IgG antibody response in pregnant women at delivery.

BACKGROUND: The prevalence of COVID-19 infection during pregnancy is not known. COVIPREG is a prospective French multicenter study to assess the seroprevalence at the time of delivery and the maternal and neonatal impact of COVID-19 infection during pregnancy. In order to study factors associated with poor outcomes after COVID-19 Infection during pregnancy and adapt the sample size of the study, a preliminary assessment of the prevalence of SARS-CoV-2 IgG was planned after 500 inclusions in a one perinatal center of Paris area. OBJECTIVES: To assess the prevalence of SARS-CoV-2 IgG antibody response in pregnant women at the time of delivery during the COVID-19 pandemia. STUDY DESIGN: A prospective observational study at Cochin hospital (Level III maternity). Patients admitted for delivery were offered to participate to the study. Each patient participating to the study was tested for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. RESULTS: Among the 529 patients included in the COVIPREG study between April 29 and June 26, 529 were assessed for SARS-CoV-2 IgG antibody response and 25 had a positive test, ie 4.7 % with a confidence interval at 95 % [3.0 %-6.9 %]). CONCLUSIONS: Four months after the beginning of the infection in Paris, the seroprevalence of SARS-CoV-2 IgG in pregnant women at the time of delivery is low. Studies evaluating the impact of COVID-19 infection during pregnancy should take this information in account in order to adapt the sample size.

Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France.

BACKGROUND: To fight the COVID-19 pandemic, lockdown has been decreed in many countries worldwide. The impact of pregnancy as a severity risk factor is still debated, but strict lockdown measures have been recommended for pregnant women. OBJECTIVES: To evaluate the impact of the COVID-19 pandemic and lockdown on the seroprevalence and circulation of SARS-CoV-2 in a maternity ward in an area that has been significantly affected by the virus. STUDY DESIGN: Prospective study at the Antoine Béclère Hospital maternity ward (Paris area, France) from May 4 (one week before the end of lockdown) to May 31, 2020 (three weeks after the end of lockdown). All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well concomitant SARS-CoV-2 RT-PCR on one nasopharyngeal sample. RESULTS: A total of 249 women were included. Seroprevalence of SARS-CoV-2 was 8%. The RT-PCR positive rate was 0.5%. 47.4% of the SARS-CoV-2-IgG-positive pregnant women never experienced any symptoms. A history of symptoms during the epidemic, such as fever (15.8%), myalgia (36.8%) and anosmia (31.6%), was suggestive of previous infection. CONCLUSIONS: Three weeks after the end of French lockdown, SARS-CoV-2 infections were scarce in our region. A very high proportion of SARS-CoV-2-IgG-negative pregnant women, which is comparable to that of the general population, must be taken into consideration in the event of a resurgence of the pandemic. The traces of a past active circulation of the virus in this fragile population during the spring wave should encourage public health authorities to take specific measures for this independent at-risk group, in order to reduce viral circulation in pregnant patients.

Added-Value of Endometrial Biopsy in the Diagnostic and Therapeutic Strategy for Pelvic Actinomycosis.

The particularity of pelvic actinomycosis lies in the difficulty of establishing the diagnosis prior to treatment. The objective of this retrospective bicentric study was to evaluate the pertinence and efficacy of the different diagnostic tools used pre- and post-treatment in a cohort of patients with pelvic actinomycosis. The following data were collected: clinical, paraclinical, type of treatment, and the outcome and pertinence of the two diagnostic methods, bacteriological or histopathological, were evaluated. Twenty-seven women were included, with a pre-treatment diagnosis proposed for 66.7% (n = 18) of them. The diagnosis was established in 13.6% (n = 3) of cases through bacteriological samples, and in 93.8% (n = 15) of cases through histopathological samples, with endometrial biopsy positive in 100% of cases. The treatment was surgical with antibiotics for 55.6% (n = 15) of patients, medical with antibiotic therapy for 40.7% (n = 11) of patients, and surgical without antibiotics for one patient. All patients achieved recovery without recurrence, with a median follow-up of 96 days (4-4339 days). Our study suggested an excellent performance of histopathological analysis, and in particular endometrial biopsy, in the diagnosis of pelvic actinomycosis. This tool allowed early diagnosis and, in some cases, the use of antibiotic therapy alone, making it possible to avoid surgery.

Usefulness and reliability of cell free fetal DNA screening for main trisomies in case of atypical profile on first trimester maternal serum screening.

BACKGROUND: Patients with atypical values of HCG and/or PAPP-A are at higher risk of chromosomal abnormality and vascular complications of pregnancy. The performance of cfDNA in this particular population has not yet been evaluated. OBJECTIVES: The primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy's vascular complications. METHOD: Between June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy's vascular complications. RESULTS: Among the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4-100) and specificity 100% (458/458) (IC 95% 99.2-100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79-0.96, p = 0.006). CONCLUSION: cfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.

Management of Cytomegalovirus Seroconversion during Pregnancy in France.

INTRODUCTION: Guidelines for the management of cytomegalovirus (CMV) infection of the fetus are rare. Our main objective was to evaluate how health care practitioners in France manage cases of CMV seroconversion during pregnancy. MATERIAL AND METHODS: A questionnaire was e-mailed to health care practitioners potentially concerned by CMV seroconversion during pregnancy. They were asked if they would recommend amniocentesis, fetal cerebral MRI examination and fetal blood analysis (FBA), depending on the ultrasound results. They then had to indicate whether they would accept termination of pregnancy (TOP), depending on the results of these examinations. RESULTS: A total of 380 health care practitioners responded, mainly obstetricians (73.9%) and midwives (20.2%). Overall, 57% of respondents recommended amniocentesis in the case of CMV seroconversion during the first trimester of pregnancy, ultrasound findings being normal. In cases of positive amniocentesis and a major ultrasound abnormality, 84.5% of respondents would perform cerebral MRI, and 44.4% would perform FBA. In this case, the rate of acceptance of TOP was not significantly different whether the examinations were normal (337/372, 90.6%) or not performed (339/374, 93.3%; p = 0.17). DISCUSSION: Amniocentesis is too infrequently used and should be encouraged. The results of MRI and FBA are often not taken into account in the final decision concerning TOP. Guidelines are needed to clarify the management of CMV seroconversion during pregnancy.