Placental T2* and BOLD effect in response to hyperoxia in normal and growth-restricted pregnancies: multicenter cohort study.

OBJECTIVES: Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non-invasive in-vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). METHODS: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non-FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5-Tesla MRI system, the same multi-echo gradient-recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* - baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non-FGR), presence/absence of Doppler anomalies and birth weight (small-for-gestational age (SGA) vs non-SGA). RESULTS: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5-48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1-48.5%) vs 33.7% (22.7-47.4%); P = 0.95). Baseline T2* Z-score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non-FGR pregnancies (median, -1.27 (IQR, -4.87 to -0.10) vs 0.33 (IQR, -0.81 to 1.02); P = 0.001). Baseline T2* Z-score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non-SGA neonate (n = 62) (median, -0.75 (IQR, -3.48 to 0.29) vs 0.35 (IQR, -0.79 to 1.05); P = 0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Brain cortical maturation assessed by magnetic resonance imaging in unaffected or mildly affected fetuses with cytomegalovirus infection.

OBJECTIVES: To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. METHODS: This was a retrospective case-control study of consecutive pregnancies with a CMV-infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low-risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV-DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto-occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non-parametric trend analysis. RESULTS: Twenty-four CMV-infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV-infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9-9.9) mm vs 3.9 (IQR, 2.6-5.3) mm; left side, 7.5 (IQR, 6.0-10.9) mm vs 4.2 (IQR, 3.2-5.3) mm), significantly decreased parieto-occipital sulcus depth (right side, 12.6 (IQR, 11.3-13.5) mm vs 15.9 (IQR, 13.5-17.3) mm; left side, 12.3 (IQR, 10.6-13.5) mm vs 16.0 (IQR, 13.3-17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4-16.3) mm vs 17.5 (IQR, 16.1-18.7) mm; left side, 14.6 (IQR, 14.1-15.6) mm vs 16.7 (IQR, 15.6-18.9) mm) (P < 0.001 for all). Compared with controls, CMV-infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8-45.8°) vs 48.9° (IQR, 38.4-64.7°); left side, 40.9° (IQR, 34.2-45.8°) vs 48.2° (IQR, 41.9-60.7°)) and lower (right side, 41.6° (IQR, 34.4-49.2°) vs 48.9° (IQR, 40.6-60.9°); left side, 42.2° (IQR, 38.8-46.9°) vs 48.9° (IQR, 39.5-57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV-infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto-occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small-for-gestational age as a confounding factor. CONCLUSIONS: Unaffected and mildly affected CMV-infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non-severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

New data on efficacy of valacyclovir in secondary prevention of maternal-fetal transmission of cytomegalovirus.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is the leading cause of non-genetic hearing and neurological deficits. The aim of our study was to evaluate the efficacy and safety of valacyclovir (VCV) treatment in preventing CMV transmission to the fetus after maternal primary infection. METHODS: This was a retrospective, multicenter study evaluating the rate of maternal-fetal CMV transmission in pregnancies with maternal primary CMV infection treated with VCV at a dosage of 8 g per day (VCV group) compared with a control group of untreated women. Each case underwent virological testing to confirm maternal primary infection and to provide accurate dating of onset of infection. The primary outcome was the presence of congenital CMV infection at birth diagnosed based on polymerase chain reaction analysis of saliva, urine and/or blood samples. The efficacy of VCV treatment was assessed using logistic regression analysis adjusted for a propensity score. RESULTS: In total, 143 patients were included in the final analysis, of whom 59 were in the VCV group and 84 were in the untreated control group. On propensity-score-adjusted analysis, VCV treatment was significantly associated with an overall reduction in the rate of maternal-fetal CMV transmission (odds ratio, 0.40 (95% CI, 0.18-0.90); P = 0.029). The rate of maternal-fetal CMV transmission, determined at birth, in the VCV vs control group was 7% (1/14) vs 10% (1/10) after periconceptional maternal primary infection (P = 1.00), 22% (8/36) vs 41% (19/46) after first-trimester maternal primary infection (P = 0.068) and 25% (2/8) vs 52% (14/27) after second-trimester maternal primary infection (P = 0.244). When analyzing the efficacy of VCV treatment according to maternal viremia at treatment initiation, there was a trend towards greater efficacy when patients were viremia-positive (21% vs 43%; P = 0.072) compared with when they were viremia-negative (22% vs 17%; P = 0.659). Maternal side effects associated with VCV were mild and non-specific in most cases. CONCLUSION: Our findings indicate that VCV treatment of pregnant women with primary CMV infection reduces the risk of maternal-fetal transmission of CMV and may be effective in cases with primary infection in the first and second trimesters. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Caesarean section in the second delivery to prevent anal incontinence after asymptomatic obstetric anal sphincter injury: the EPIC multicentre randomised trial.

OBJECTIVE: To determine whether planned caesarean section (CS) for a second delivery protects against anal incontinence in women with obstetric anal sphincter lesions. DESIGN: Randomised trial. SETTING: Six maternity units in the Paris area. SAMPLE: Women at high risk of sphincter lesions (first delivery with third-degree laceration and/or forceps) but no symptomatic anal incontinence. METHODS: Endoanal ultrasound was performed in the third trimester of the second pregnancy. Women with sphincter lesions were randomised to planned CS or vaginal delivery (VD). MAIN OUTCOME MEASURES: Anal incontinence at 6 months postpartum. Secondary outcomes were urinary incontinence, sexual morbidity, maternal and neonatal morbidities and worsening of external sphincter lesions. RESULTS: Anal sphincter lesions were detected by ultrasound in 264/434 women enrolled (60.8%); 112 were randomised to planned VD and 110 to planned CS. At 6-8 weeks after delivery, there was no significant difference in anal continence between the two groups. At 6 months after delivery, median Vaizey scores of anal incontinence were 1 (interquartile range 0-4) in the CS group and 1 (interquartile range 0-3) in the VD group (P = 0.34). There were no significant differences for urinary continence, sexual functions or for other maternal and neonatal morbidities. CONCLUSIONS: In women with asymptomatic obstetric anal sphincter lesions diagnosed by ultrasound, planning a CS had no significant impact on anal continence 6 months after the second delivery. These results do not support advising systematic CS for this indication. TWEETABLE ABSTRACT: Caesarean section for the second delivery did not protect against anal incontinence in women with asymptomatic obstetric anal sphincter lesions.

Early- and late-onset postpartum depression exhibit distinct associated factors: the IGEDEPP prospective cohort study.

OBJECTIVE: To identify risk factors for early- and late-onset postpartum depression (PPD) among a wide range of variables, including sociodemographic characteristics, childhood trauma, stressful life events during pregnancy and history of personal and family psychiatric disorders, and to assess the contribution of each risk factor. DESIGN: Nested case-control study in a prospective longitudinal cohort study. SETTING: Eight maternity departments in the Paris metropolitan area, France. SAMPLE: A cohort of 3310 women with deliveries between November 2011 and June 2016. METHODS: Cases were women with early- or late-onset PPD. Controls were women without depression during pregnancy or the postpartum period. Logistic regression adjusted on sociodemographic variables was performed for each outcome and a multivariable model was proposed based on a stepwise selection procedure. MAIN OUTCOME MEASURES: Early- and late-onset PPD assessed at 2 months and 1 year postpartum, respectively. RESULTS: Stressful life events during pregnancy have a dose-response relationship with both early- and late-onset PPD. CONCLUSIONS: Early- and late-onset PPD presented distinct patterns of determinants. These results have important consequences in terms of prevention and specific care. TWEETABLE ABSTRACT: Early- and late-onset postpartum depression are associated with stressful life events and psychiatric history.

Transvaginal ultrasound probes are human papillomavirus-free following low-level disinfection: cross-sectional multicenter survey.

OBJECTIVES: To assess the frequency of detection of high-risk human papillomavirus (hrHPV) on transvaginal ultrasound (TVS) probes and keyboards and evaluate operator compliance with national recommendations for prevention of cross-infection during TVS. METHODS: This was a multicenter observational survey involving 46 public and private centers, in the Paris region of France, in which at least five consecutive TVS examinations were performed per day. We audited 676 TVS procedures. We recorded preventive hygiene actions undertaken by the operator at three stages: (1) during TVS; (2) during probe disinfection; and (3) during preparation of the probe for the next TVS. After probe disinfection, we collected one sample from the bare probe and one from the ultrasound keyboard; following probe preparation for the next examination, an additional sample was obtained from the covered probe. The samples were tested for presence of hrHPV DNA using the Cobas® 4800 System. RESULTS: We did not detect hrHPV DNA in samples collected from uncovered or covered probes (0%; 95% CI, 0.00-0.55%). Keyboard samples were positive for hrHPV in two cases (0.3%; 95% CI, 0.04-1.07%). During TVS, the operator avoided touching the keyboard with a hand that had touched the patient's vulva in 86% of cases and held the probe with a gloved hand in 68%. Before probe disinfection, the operator wore new gloves, or performed hand disinfection in 8% of cases. The probe disinfection technique used was adequate in 87% of cases, not performed at all in 12% and insufficient in 1%. Before preparing the probe for the next scan, the operators disinfected their hands or used new gloves in 81% of cases. The probe cover and the coupling gel used complied with recommendations in 98% and 46% of cases, respectively. Of the seven preventive hygiene actions recommended in national guidelines, all were performed in 2%, three to six in 95% and two in 3% of observations. In four (9%) centers, disinfection was not performed in over half the observations. CONCLUSIONS: No evidence of hrHPV DNA was found on TVS probes and probe covers following low-level disinfection, despite suboptimal compliance with hygiene guidelines. Routine TVS practice could be made easier and safer with a global approach to probe disinfection and hand hygiene. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Performance of semiconductor sequencing platform for non-invasive prenatal genetic screening for fetal aneuploidy: results from a multicenter prospective cohort study in a clinical setting.

OBJECTIVE: To validate and evaluate the performance metrics of the high-throughput semiconductor sequencing platform, Ion Proton®, in non-invasive prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical setting. METHODS: This prospective cohort study included 2505 pregnant women from eight academic genetics laboratories (695 high risk for trisomy 21 (risk ≥ 1/250) pregnancies in a validation study, and 1810 such pregnancies, without ultrasound anomalies, in a real-life NIPS clinical setting). Outcome was available for all cases in the validation cohort and for 521 in the clinical cohort. Cell-free DNA from plasma samples was sequenced using the Ion Proton sequencer, and sequencing data were analyzed using the open-access software, WISECONDOR. Performance metrics for detection of trisomies 21, 18 and 13 were calculated based on either fetal karyotype result or clinical data collected at birth. We also evaluated the failure rate and compared three methods of fetal fraction quantification (RASSF1A assay, and DEFRAG and SANEFALCON software). RESULTS: Results from both cohorts were consistent and their gestational age was not significantly different so their data were combined to increase the sample size for analysis. Sensitivities and specificities, respectively, were as follows: for trisomy 21, 98.3% (95% CI, 93.5-99.7%) and 99.9% (95% CI, 99.4-100%); for trisomy 18, 96.7% (95% CI, 80.9-99.8%) and 100% (95% CI, 99.6-100%); and for trisomy 13, 94.1% (95% CI, 69.2-99.7%) and 100% (95% CI, 99.6-100%). Our failure rate was 1.2% initially and as low as 0.6% after retesting some of the failed samples. Fetal fraction estimation by the RASSF1A assay was consistent with DEFRAG results, and both were adequate for routine diagnosis. CONCLUSIONS: We describe one of the largest studies evaluating Ion Proton-based NIPS and the first clinical study reporting pregnancy outcome in a large series of patients. This platform is highly efficient in detecting the three most common trisomies. Our protocol is robust and can be implemented easily in any medical genetics laboratory. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Adverse effects of maternal enterovirus infection on the pregnancy outcome: a prospective and retrospective pilot study.

BACKGROUND: Enteroviruses account for about one billion infections worldwide each year, the majority remain asymptomatic. Data on enterovirus infections during pregnancy appear to be very rare. Several cases have been reported in the literature of fetal and neonatal complications attributed to these viruses, but prospective data on these infections during pregnancy are not available. OBJECTIVE: To estimate the prevalence of enterovirus infections in febrile syndromes in pregnant women, and in case of in utero fetal death (IUFD). METHODS: Ttri-centric observational cohort study. We performed prospective inclusion for patients with fever during a four-month period. We also analyzed the amniotic fluid in patients with unexplained IUFD retrospectively during a five-year period. Investigations of enteroviruses are made by RT-PCR from routine biological samples (amniocentesis, RT-PCR in maternal blood or CSF). RESULTS: Prospectively, 33 patients were included during the study period. We have identified 4 cases of confirmed enterovirus infection (12.4%). We have recorded a severe form of perinatal enterovirus infection involving the vital prognosis of the newborn. In the retrospective cohort of 75 IUFD cases, we had only one case of enterovirus-positive RT-PCR in amniotic fluid during 5 years, meaning a frequency of 1.3%. We did not had any positive EV case in case of early miscarriage, but the limited number of inclusions cannot help us to conclude. CONCLUSION: Enteroviruses are probably an underestimated cause of obstetric and neonatal complications. Investigation of enterovirus by PCR should be discussed during pregnancy and peripartum in case of febrile syndrome with no obvious bacterial cause, and unexplained IUFD.

Intrapartum group B Streptococcus screening in the labor ward by Xpert® GBS real-time PCR.

Group B Streptococcus (GBS) is the leading cause of neonatal infections in industrialized countries. Intrapartum antibiotic prophylaxis (IAP) given to colonized parturients is a key step for the prevention of neonatal early-onset infection. We compared the performances of Xpert® GBS polymerase chain reaction (PCR) (Cepheid, Sunnyvale, CA, USA) as a point-of-care system in labor wards to standard culture for intrapartum GBS detection. Pregnant women with a GBS-positive antenatal screening were prospectively included. A vaginal double swab was collected at the time of delivery for point-of-care Xpert® GBS PCR and GBS culture. A total of 565 pregnant women were included. Valid Xpert® GBS results were obtained for 488 (86.4%) women on the first attempt. Repeat testing improved the PCR success to 516 (91.3%) women. Among the 305 women positive for GBS by culture at delivery, only 238 (78.0%) were positive by Xpert® GBS PCR, cycle thresholds being correlated to culture quantification. Among 260 women negative for GBS culture, 56 (21.5%) were positive by Xpert® GBS PCR, including 50 where IAP was initiated before vaginal sampling. Overall, among the 565 women with GBS antenatal positive culture, only 335 (59.3%) were still positive at delivery whatever the technique used, resulting in unnecessary IAP for 40% of them. This large cohort study comparing intrapartum to antepartum GBS detection provides evidence that (i) Xpert® GBS PCR might be a valuable solution for intrapartum GBS detection compared to culture-based strategies and (ii) laboratory training of non-specialized staff is mandatory to reach the performances required for point-of-care tests.

Association between inadequate antenatal care utilisation and severe perinatal and maternal morbidity: an analysis in the PreCARE cohort.

OBJECTIVE: Because the effectiveness of antenatal care in reducing pregnancy complications is still discussed despite widespread recommendations of its use, we sought to assess the association between utilisation of recommended antenatal care and severe maternal (SMM) and perinatal morbidity (SPM). DESIGN: Prospective cohort study. SETTING: Four maternity units around Paris in 2010-2012. SAMPLE: 9117 women with singleton pregnancies. METHODS: Logistic regression models adjusted for maternal social, demographic and medical characteristics. MAIN OUTCOME MEASURES: Antenatal care utilisation was assessed by: (1) initiation of care after 14 weeks, (2) < 50% of recommended visits made, according to gestational age, (3) absence of the first, second or third trimester ultrasounds, (4) two modified Adequacy of Prenatal Care Utilisation indexes, combining these components. The two main outcomes were composite variables of SMM and SPM. RESULTS: According to the modified Adequacy of Prenatal Care Utilisation index, 34.6% of women had inadequate antenatal care utilisation; the incidence of severe maternal morbidity (SMM) was 2.9% and severe perinatal morbidity (SPM) 5.5%. A percentage of recommended visits below 50% (2.6% of women) was associated with SMM [adjusted odds ratio (OR) 2.40 (1.38-4.17)] and SPM [aOR 2.27 (1.43-3.59)]. Late initiation of care (17.0% of women) was not associated with SMM or SPM. Failure to undergo the recommended ultrasounds (16, 17 and 22% of women) was associated with SPM. Inadequate antenatal care utilisation according to the index was associated with SPM [aOR 1.37 (1.05-1.80)]. CONCLUSION: Inadequate antenatal care utilisation is associated with SMM and SPM, to degrees that vary with the component of care and the outcome considered. TWEETABLE ABSTRACT: Inadequate antenatal care utilisation is associated with severe maternal and perinatal morbidity.

Reference values for biochemical tests during pregnancy: analysis of the PRECAREbio Cohort and correlation with precarious status.

OBJECTIVE: To establish normal current values of various biochemical parameters during pregnancy in the northern area of Paris (France) in a subgroup from the PreCARE cohort and to study their changes according to the term of pregnancy, and to determine the influence of maternal precarity. DESIGN: The PreCAREbio cohort of pregnant women was defined in the PreCARE study, a multicenter cohort study. SETTING: Participants completed detailed questionnaires at enrolment and immediately postpartum. Data were collected prospectively. 26 biochemical parameters were longitudinally assessed. POPULATION: All women registered to deliver or who delivered at one of the four participating university hospitals in Paris between October 2010 and November 2011 were eligible for study inclusion (n=10,419). METHODS: We studied 26 biochemical markers during pregnancy and the influence of maternal social deprivation. MAIN OUTCOME MEASURES: Baseline values for 26 biochemical markers and their changes according to the term of pregnancy, and the influence of maternal social deprivation on these biochemical markers. RESULTS: 386 patients with 1733 blood samples recruited in one of the four centers in the PreCARE cohort were included. Baseline concentrations (median, 2.5th and 97.5th percentile) for each marker and did not differ at the different time points. Mean concentrations of each biochemical marker did not differ between socially deprived women and non-socially deprived women. CONCLUSIONS: We have established normal values for 26 biochemical parameters during pregnancy. We have also shown no difference in these values between socially deprived and non- socially deprived women.

Placental transfer of maraviroc in an ex vivo human cotyledon perfusion model and influence of ABC transporter expression.

Nowadays, antiretroviral therapy is recommended during pregnancy to prevent mother-to-child transmission of HIV. However, for many antiretroviral drugs, including maraviroc, a CCR5 antagonist, very little data exist regarding placental transfer. Besides, various factors may modulate this transfer, including efflux transporters belonging to the ATP-binding cassette (ABC) transporter superfamily. We investigated maraviroc placental transfer and the influence of ABC transporter expression on this transfer using the human cotyledon perfusion model. Term placentas were perfused ex vivo for 90 min with maraviroc (600 ng/ml) either in the maternal-to-fetal (n = 10 placentas) or fetal-to-maternal (n = 6 placentas) direction. Plasma concentrations were determined by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fetal transfer rates (FTR) and clearance indexes (CLI) were calculated as ratios of fetal to maternal concentrations at steady state (mean values between 30 and 90 min) and ratios of FTR of maraviroc to that of antipyrine, respectively. ABC transporter gene expression levels were determined by quantitative reverse transcription (RT)-PCR and ABCB1 protein expression by Western blotting. For the maternal-to-fetal direction, the mean FTR and CLI were 8.0% ± 3.0 and 0.26 ± 0.07, respectively, whereas the mean CLI was 0.52 ± 0.23 for the fetal-to-maternal direction. We showed a significant inverse correlation between maraviroc CLI and ABCC2, ABCC10, and ABCC11 placental gene expression levels (P < 0.05). To conclude, we report a low maraviroc placental transfer probably involving ABC efflux transporters and thus in all likelihood associated with a limited fetal exposition. Nevertheless, these results would need to be supported by in vivo data obtained from paired maternal and cord blood samples.

Non-disclosure of a pregnant woman's HIV status to her partner is associated with non-optimal prevention of mother-to-child transmission.

Our objective was to study relations between non-disclosure of HIV to partner, socio demographics and prevention of HIV mother-to-child transmission (PMTCT), among HIV-infected pregnant women enrolled in the French Perinatal Cohort (ANRS-EPF-CO1) from 2005 to 2009 (N = 2,952). Fifteen percent of the women did not disclose their HIV status to their partner. Non-disclosure was more frequent in women diagnosed with HIV infection late in pregnancy, originating from Sub-Saharan Africa or living alone, as well as when the partner was not tested for HIV. Non-disclosure was independently associated with non optimal PMTCT: late initiation of antiretroviral therapy, detectable viral load at delivery and lack of neonatal prophylaxis. Nonetheless, the rate of transmission did not differ according to disclosure status. Factors associated with non-disclosure reflect vulnerability and its association with non optimal PMTCT is a cause for concern although the impact on transmission was limited in this context of universal free access to care.

Impact of variants of SARS-CoV-2 on obstetrical and neonatal outcomes.

BACKGROUND: SARS-CoV-2 can lead to several types of complications during pregnancy. Variant surges are associated with different severities of disease. Few studies have compared the clinical consequences of specific variants on obstetrical and neonatal outcomes. Our goal was to evaluate and compare disease severity in pregnant women and obstetrical or neonatal complications between variants of SARS-CoV-2 that have circulated in France over a two-year period (2020-2022). METHOD: This retrospective cohort study included all pregnant women with a confirmed SARS-CoV-2 infection (positive naso-pharyngeal RT-PCR test) from March 12, 2020 to January 31, 2022, in three tertiary maternal referral obstetric units in the Paris metropolitan area, France. We collected clinical and laboratory data for mothers and newborns from patients' medical records. Variant identification was either available following sequencing or extrapolated from epidemiological data. RESULTS: There were 234/501 (47%) Wild Type (WT), 127/501 (25%) Alpha, 98/501 (20%) Delta, and 42/501 (8%) Omicron. No significative difference was found regarding two composite adverse outcomes. There were significantly more hospitalizations for severe pneumopathy in Delta variant than WT, Alpha and Omicron respectively (63% vs 26%, 35% and 6%, p<0.001), more frequent oxygen administration (23% vs 12%, 10% and 5%, p = 0,001) and more symptomatic patients at the time of testing with Delta and WT (75% and 71%) versus Alpha and Omicron variants (55% and 66% respectively, p<0.01). Stillbirth tended to be associated with variants (p = 0.06): WT 1/231 (<1%) vs 4/126 (3%), 3/94 (3%), and 1/35 (3%) in Alpha, Delta and Omicron cases respectively. No other difference was found. CONCLUSION: Although the Delta variant was associated with more severe disease in pregnant women, we found no difference regarding neonatal and obstetrical outcomes. Neonatal and obstetrical specific severity may be due to mechanisms other than maternal ventilatory and general infection.

Etravirine concentrations in the cervicovaginal compartment in HIV-1-infected women receiving etravirine-containing antiretroviral therapy: DIVA 02 study.

We studied the penetration of etravirine and HIV shedding in the genital tract among 12 HIV-1-infected women receiving an etravirine-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median etravirine concentrations were 663 ng/ml in BP and 857 ng/ml in CVF, with a CVF/BP etravirine ratio of approximately 1.2. This good penetration of etravirine may contribute to the control of viral replication in the female genital tract.

[SARS-Cov-2 vaccine's acceptance among pregnant women-A cross-sectional survey]. / Acceptabilité du vaccin-Sars CoV-2 chez les femmes enceintes, une enquête transversale par questionnaire.

OBJECTIVE: SARS-CoV-2 is more likely to cause severe cases in pregnant women. They were part of the priority groups since April 2021 to benefit from SARS-CoV-2 vaccination before its extent to general population. This contribution aims to evaluate, in the postpartum period, the achievement of COVID-19 vaccination and factors associated in women during their pregnancy. MATERIAL AND METHOD: Multicenter cross-sectional survey study conducted from September to December 2021 with online self-questionnaire. All postpartum patients hospitalized in one of the 6 participating maternity hospitals were invited to answer. The questionnaire asked patients about their demographic characteristics, vaccination modalities, vaccine tolerance, and their general perception of vaccination. RESULTS: Of the 371 women who responded, the vaccination rate was 65.7% (IC95% [60.8-70.4]), whom 98.8% entirely during pregnancy. Associated factors with vaccination during pregnancy were older age, higher socio-professional category, and prior information provided by health professionals. Factors that appear to motivate vaccination were personal protection and protection of the newborn. Finally, main factors negatively influencing the vaccination process were the fear of vaccine side effects and the negative perception of vaccines in general. DISCUSSION: Acceptability and information about the vaccine by health professionals is in constant improvement. Information campaigns should be continued to improve the acceptability of vaccination, in light of the accumulating data.

[Efficiency of Bakri intra uterine tamponade balloon use in postpartum hemorrhage: Before and after study]. / Efficacité de l'utilisation du ballonnet de tamponnement intra-utérin dans l'hémorragie du post-partum. Étude rétrospective monocentrique avant/après.

OBJECTIVE: To assess the impact of the introduction of intrauterine balloon tamponade on second-line management practices for post-partum hemorrhage (PPH). METHOD: This retrospective study was conducted in a tertiary care centre where arterial embolisation was not available. Two periods were compared, before (2008-2010) and after (2015-2017) the introduction of an intrauterine tamponade balloon protocol using the Bakri balloon. All consecutive patients with PPH refractory to sulprostone in the two periods were included. Outcomes studied were the incidence of invasive procedures (conservative surgery, embolisation, hysterectomy) as well as transfer to centres with arterial embolisation facilities. RESULTS: A total of 109 patients had refractory PPH, 44 in the first period and 65 in the second period. The proportion of all PPH cases which required sulprostone did not differ between the periods (24.2 and 29.3%, respectively, P=0.25). There were significant decreases between the first and the second period in the proportion requiring a transfer to an embolisation centre (79.6% during period 1, vs. 6.2% respectively, P<0.001), embolisation (20.6% vs. 0%, P<0.001), uterine compression sutures (13.6% vs. 3.1% P=0.04) and surgical management (22.7% vs. 7.7%, P=0.025). The decrease in the incidence of hysterectomy did not reach statistical significance (11,4 vs. 1,5%, P=0.095). Among 29 cases of PPH following cesarean sections (14 in the first period and 15 in the second period), we observed a significant decrease in transfer rates (66.7% vs. 0%, P<0.01), as well as decreases in embolisation (26.7% vs. 0%, P=0.10) and invasive procedures (60% vs. 28.7%, P=0.089), which did not reach statistical significance. CONCLUSION: The introduction of intrauterine tamponade was associated with a decrease in the need for invasive procedures. In a centre without access to on-site arterial embolisation, transfer rates were reduced improving patient comfort and reducing costs.

[Toxoplasmosis in pregnancy: Practical Management]. / Toxoplasmose pendant la grossesse : proposition actuelle de prise en charge pratique.

The burden of congenital toxoplasmosis has become small in France today, in particular as a result of timely therapy for pregnant women, fetuses and newborns. Thus, the French screening and prevention program has been evaluated and recently confirmed despite a decline over time in the incidence of toxoplasmosis. Serological diagnosis of maternal seroconversion is usually simple but can be difficult when the first trimester test shows the presence of IgM, requiring referral to an expert laboratory. Woman with confirmed seroconversion should be referred quickly to an expert center, which will decide with her on treatment and antenatal diagnosis. Although the level of proof is moderate, there is a body of evidence in favor of active prophylactic prenatal treatment started as early as possible (ideally within 3 weeks of seroconversion) to reduce the risk of maternal-fetal transmission, as well as symptoms in children. The recommended therapies to prevent maternal-fetal transmission are: (1) spiramycin in case of maternal infection before 14 gestational weeks; (2) pyrimethamine and sulfadiazine (P-S) with folinic acid in case of maternal infection at 14 WG or more. Amniocentesis is recommended to guide prenatal and neonatal care. If fetal infection is diagnosed by PCR on amniotic fluid, therapy with P-S should be initiated as early as possible or continued in order reduce the risk of damage to the brain or eyes. Further research is required to validate new approaches to preventing congenital toxoplasmosis.

Prenatal diagnosis of 18q-syndrome: a case of fetal mosaicism with a normal karyotype in chorionic villi.

We report a case of fetoplacental discrepancy with normal karyotype on chorionic villi and deletion of the long arm of chromosome 18 on amniotic fluid. Cytogenetic tests were repeated because of a short corpus callosum on ultrasound examination. This 18q-syndrome has been reported to be associated with poor neurodevelopmental outcome.