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Background & Aims: Vitamin D status during pregnancy and in newborns has never been studied in France. This study aims at determining the vitamin D status during the first and third trimesters of pregnancy (T1, T3) and in cord blood (CB) in the middle-north of France., Methods: We conducted a prospective cohort study in five French centers (latitude 47.22 to 48.86°N). Serum 25(OH)-vitamin D (25(OH)D) concentrations were measured using a radioimmunoassay during T1, T3 and in CB. According to the French guidelines, pregnant women received cholecalciferol, 100,000 IU, in the seventh month., Results: Between April 2012 and July 2014, 2832 women were included, of whom 2803 were analyzed (mean ± SD age: 31.5 ± 5.0 years; phototypes 5-6: 21.8%). Three and 88.6% of participants received supplementation during the month before inclusion and in the seventh month, respectively. At T1, T3, and CB, mean 25(OH)D concentrations were 21.9 ± 10.4, 31.8 ± 11.5, and 17.0 ± 7.2 ng/mL, respectively, and 25(OH)D was <20 ng/mL in 46.5%, 14.0%, and 68.5%, respectively. At T1, body mass index ≥25 kg/m 2 , dark phototypes, sampling outside summer, and no supplementation before inclusion were independently associated with vitamin D insufficiency (25(OH)D < 20 ng/mL). Women who received cholecalciferol supplementation in month 7 had higher 25(OH)D at T3 than non-supplemented women (32.5 ± 11.4 versus 25.8 ± 11.4 ng/mL, p = <0.001) and marginally higher 25(OH)D in CB (17.2 ± 7.2 versus 15.5 ± 7.1 ng/mL, p = 0.004)., Conclusions: Despite the recommended supplementation, vitamin D insufficiency is frequent during pregnancy and in newborns in France., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide., Methods: This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications., Discussion: The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

Fetal cells circulating in the peripheral blood of pregnant women are a potential target for noninvasive genetic analyses. They include epithelial (trophoblastic) cells, which are larger than peripheral blood leukocytes. We enriched circulating trophoblastic cells using the isolation by size of epithelial tumor cells (ISET) method. Peripheral blood was obtained at 11 to 12 weeks of pregnancy. Cells isolated by ISET were stained by hematoxylin and eosin or by immunohistochemistry. Large epithelial cells were microdissected and fetal cell identification was obtained by polymerase chain reaction with short tandem repeats and/or Y-specific primers. By analyzing only 2 ml of blood, we found a variable number (n = 1 to 7) of Y-positive cells (overall 15 of 23) in all of the six mothers carrying a male fetus. In contrast, none of the 26 cells isolated from seven mothers carrying a female fetus scored positive. Eleven cells were analyzed by using short tandem repeat-specific markers: six of them showed a fetal profile and five showed a maternal profile consistently with Y-specific results. Only one-fifth of the single cell DNA was used for fetal cell assessment, leaving enough material for further genetic tests. We also show that the ISET approach allows the performance of fluorescence in situ hybridization analyses and the detection of DNA point mutations in single microdissected cells. We conclude that this is a powerful approach to enrich circulating fetal cells and prove their fetal origin, and that it may have implications for noninvasive prenatal diagnosis of genetic disorders.

Recent literature from China, Italy, and the United States suggests that pregnant women are not at higher risk for severe forms of coronavirus disease (COVID-19) from infection with severe acute [...]

This study aimed to describe the characteristics of fetal demise after SARS-CoV-2 infections and clarify whether it is associated with clinical severity, placental lesions, or malformations or due to actual fetal infections. PubMed and Web of Science databases were searched between December 1, 2019, and April 30, 2022. Cohort, cross-sectional, and case-control studies and case series or case reports describing stillbirths or late miscarriages (ie, pregnancy loss occurring between 14 and 22 weeks of gestation, before and after the onset of labor) from mothers with SARS-CoV-2 infection during pregnancy (demonstrated by at least 1 positive real-time reverse transcription-polymerase chain reaction from nasopharyngeal swabs and/or SARS-CoV-2 placental infection). No language restriction was applied; cases with other causes possibly explaining the fetal demise were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines were followed. The quality of the case series and case reports was evaluated using the specific Mayo Clinic Evidence-Based Practice Center tool. Maternal and clinical fetal data and placental and fetal virology and histology findings were collected. Data were summarized with descriptive statistics using the World Health Organization criteria to classify disease severity and fetal-neonatal infections. Data from 184 mothers and 190 fetuses were analyzed. No clear link to maternal clinical severity or fetal malformation was evident. Approximately 78% of fetal demise cases occurred during the second and third trimesters of pregnancy, approximately 6 to 13 days after the diagnosis of SARS-CoV-2 infection or the onset of symptoms. Most placentas (88%) were positive for SARS-CoV-2 or presented the histologic features of placentitis (massive fibrin deposition and chronic intervillositis) previously observed in transplacentally transmitted infections (85%–91%). Of note, 11 fetuses (5.8%) had a confirmed in utero transmitted SARS-CoV-2 infection, and 114 fetuses (60%) had a possible in utero transmitted SARS-CoV-2 infection. The synthesis of available data showed that fetal demise generally occurs a few days after the infection with histologic placental inflammatory lesions associated with transplacental SARS-CoV-2 transmission and eventually causing placental insufficiency. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To compare maternal complications and describe neonatal outcomes in women with severe preeclampsia at ≤ 26+0 weeks in two countries with different management policies: expectant management (Brazil) versus termination of pregnancy (France). Methods: We conducted a retrospective comparative study by reviewing the medical records of women with severe preeclampsia at ≤ 26+0 weeks, from January 2010 to June 2018, in two centers: Hospital das Clínicas da Faculdade de Medicina, in Sao Paulo, Brazil (where medical abortion is forbidden in this indication) and Hôpital Antoine-Béclère, Clamart, France (where medical termination is accepted). We collected information on maternal characteristics, laboratory tests, maternal complications and fetal and newborn characteristics. We used Student's t-test and the Mann-Whitney U nonparametric test to compare quantitative variables, and Chi-square test or Fisher's exact test to evaluate the associations between the qualitative variables. Results: There was no between-group difference in maternal complications during hospitalization (p = 0.846). In Brazil, the rate of cesarean section was 66.7%, and 20% of patients had vertical incision. The rate of spontaneous fetal death was 35.6% and among the live-born infants 26.6% were discharged from hospital. In France, one patient had a cesarean section with vertical incision. Conclusion: When comparing termination of pregnancy to expectant management in severe preeclampsia before 26 weeks, maternal complications were equivalent but maternal reproductive future might have been compromised in 20% of cases due to a higher risk of uterine rupture in subsequent pregnancies for patients having classic cesarean (vertical incision). 26.6% of children survived the neonatal period when pregnancy was pursued, however we lack information on their long-term follow-up. [ABSTRACT FROM AUTHOR]

Objective: To assess whether antibiotics used for treatment in asymptomatic second-trimester women positive for Mycoplasma or Ureaplasma spp. detected by amniotic-fluid PCR prevents preterm delivery. Design: A randomized, double-blind, placebo-controlled trial. Setting: 10 maternal fetal medicine centers in France. Population: Women with a singleton pregnancy who underwent amniocentesis between 16 and 20 weeks’ gestation (weeks) for Down syndrome screening. A sample of 238 women with PCR-positive findings per treatment group was needed to show a 50% reduction in the preterm delivery rate. Methods: Amniotic fluid was tested. Women with positive findings on real-time PCR of amniotic fluid for Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum and Ureaplasma parvum were randomized to receive josamycin or placebo. Amniotic fluid was also tested for 16S PCR. Main outcome measures: The primary outcome was delivery before 37 weeks. Results: In total, 1043 women underwent amniotic-fluid screening with specific PCR detection between July 2008 and July 2011: PCR detection failed in 27 (2.6%), and 20 (1.9%) underwent termination of pregnancy. Among the 1016 women with PCR results, 980 had available data for the primary outcome (delivery before 37 weeks) and 29 (3.0%) were positive for Ureaplasma and/or Mycoplasma spp. Because of the low rate of women with PCR-positive findings, the trial was stopped prematurely. In total, 19 women were randomized to receive placebo (n = 8) or josamycin (n = 11) and their characteristics were comparable, as was the rate of preterm delivery and secondary outcomes. In comparing all PCR-positive and -negative women regardless of treatment, PCR positivity for Ureaplasma and/or Mycoplasma spp. was not associated with any adverse pregnancy or neonatal outcome. Amniotic-fluid screening by 16S PCR showed no other bacterial colonization associated with preterm birth. Conclusions: Because of a low amniotic fluid colonization rate, the trial was interrupted. Maternal amniotic-fluid colonization by Mycoplasma and/or Ureaplasma spp. at 16–20 weeks in asymptomatic women is rare and not associated with adverse pregnancy outcomes. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia is a rare disease associated with high mortality and morbidity. Antenatal ultrasound screening identifies more than 70% of cases, providing the opportunity for in utero referral to a tertiary care center for expert assessment and perinatal management. Additional genetic and morphologic assessment may be used to rule out associated anomalies. In isolated cases, the outcome may be predicted prenatally by medical imaging. The combination of lung size and liver herniation is a widely accepted method to stratify fetuses into groups with an increasing degree of pulmonary hypoplasia and corresponding mortality rates. Ultrasound measurement of the observed to expected lung-to-head ratio (o/e LHR) is most widely used. The o/e LHR is an independent predictor of survival and short-term morbidity. Finally, evaluation of stomach position has recently been introduced as an indirect method to estimate severity of the disease in left-sided defects, as it has been shown to correlate with the proportion of intrathoracic liver. Herein, we propose a protocol for the standardized ultrasound assessment of fetuses with isolated CDH and individualized prediction of neonatal outcome. [ABSTRACT FROM AUTHOR]

Background: Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models. Methods: Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks. Results: With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice. Conclusions: Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures. [ABSTRACT FROM AUTHOR]

Background: Zika virus (ZIKV) is an arthropod-borne virus of the family Flaviviridae, genus Flavivirus. ZIKV is currently the focus of an ongoing pandemic and worldwide public health emergency. Although originally isolated in 1947, its pathogenesis was poorly known and very few documented infections were published until recently. Its route of transmission and its impact on reproduction and pregnancy have only recently begun to be disclosed.Objective and Rationale: This review summarizes the most recent knowledge about ZIKV infection and pathogenesis and focuses on its impacts on male and female genital tracts, including the risks of sexual transmission and to pregnancy. The consequences of ZIKV infection for pregnancy planning and ART are also discussed.Search Methods: The PubMed and EMBASE databases were inter-rogated using specific terms, such as 'ZIKV', 'transmission', 'male', 'female', fertility', 'pregnancy, 'semen', 'testis', 'ovary' and 'genital tract', up to 17 March 2017.Outcomes: ZIKV has long been considered a harmless virus, but increasing evidence suggests that it has adverse effects on the neurological system and on pregnancy outcomes. In mice, ZIKV slows foetal growth and damages the foetal brain. In humans, the virus is able to cross the placental barrier and to induce foetal death and major anomalies, such as microcephaly, brain defects and long-term neurologic sequelae, i.e. the 'congenital Zika syndrome'. In addition to its transmission by mosquitoes, ZIKV may be transmitted sexually. Currently available data indicate that ZIKV RNA can remain detectable in semen for several months, whereas shedding in the female genital tract appears to be rare and of short duration. Current guidance on preventing the sexual transmission of ZIKV is based on the assumption that transmission occurs from a male partner to a receptive partner. Furthermore, in mouse models, the virus can actively replicate in male genital organs and induce severe orchitis, which raises concerns about its possible impact on human male fertility.Wider Implications: These new and relevant findings have led many countries and institutions to release updated and regular guidance for preconception counselling and ART to prevent the sexual transmission of ZIKV. Progress in understanding the sexual transmission of ZIKV and its dissemination to genital systems would also help to better anticipate and control outbreaks of potentially sexually transmissible infectious agents. [ABSTRACT FROM AUTHOR]

Objectives: To validate a model predicting the risk of threatened preterm delivery and to establish the optimal threshold for this risk scoring system. Materials and methods: Two cohorts were studied: one of singleton pregnancies without preterm premature rupture of membranes (PPROM) and no cervical cerclage (cohort 1) and one of twin pregnancies without PPROM and no cervical cerclage (cohort 2). Patients were included from January 1st 2013 until December 31st 2013 by the Regional Perinatal Network of Ile de France with patients transferred because of threatened preterm delivery at 22 to 32 weeks of gestation. The individual probability of delivery within 48 hours of admission was calculated using the nomogram for every patient. Discrimination and calibration of the nomogram as well as the optimal threshold were determined using R studio. Results: The nomogram accurately predicted obstetric outcome. Discrimination and calibration were excellent, with an area under the curve (AUC) of 0.88 (95% CI 0.86–0.90) for cohort 1 and 0.73 (95% CI 0.66–0.80) for cohort 2. The optimal threshold would be 15% for cohort 1 and 10% for cohort 2. Using these thresholds, the performance characteristics of the nomogram were: sensitivity 80% (cohort 1) and 69% (cohort 2), negative predictive value 94.8% (cohort 1) and 91.3% (cohort 2). Use of the nomogram would avoid 253 unnecessary transfers in cohort 1. Conclusions: The nomogram was efficient and clinically relevant in our high risk population. A threshold set at 15% would help minimize the risk of preterm deliveries in singleton pregnancies and should reduce unnecessary, costly and stressful in utero transfer. [ABSTRACT FROM AUTHOR]

Background: Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use.Methods and Findings: We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts.Conclusions: This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 can be vertically transmitted from the mother to the fetus and the neonate. This transmission route is rare compared to the environmental or horizontal spread and therefore, the risk can be deemed inconsequential by some medical providers. However, severe, although just as rare, feto-neonatal consequences are possible: fetal demise, severe/critical neonatal COVID-19 and multi-inflammatory syndrome (MIS-N) have been described. Therefore, it is important for the clinicians to know the mechanism of vertical transmission, how to recognize this, and how to deal with neonatal COVID-19 and MIS-N. Our knowledge about this field has significantly increased in the last three years. This is a summary of the pathophysiology, diagnostics, and therapeutics of vertical SARS-CoV-2 transmission that clinicians apply in their clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the accuracy of ultrasonography and magnetic resonance imaging (MRI) in the diagnosis of placenta accreta and to define the most relevant specific ultrasound and MRI features that may predict placental invasion. Material and Methods: This study was approved by the institutional review board of the French College of Obstetricians and Gynecologists. We retrospectively reviewed the medical records of all patients referred for suspected placenta accreta to two university hospitals from 01/2001 to 05/2012. Our study population included 42 pregnant women who had been investigated by both ultrasonography and MRI. Ultrasound images and MRI were blindly reassessed for each case by 2 raters in order to score features that predict abnormal placental invasion. Results: Sensitivity in the diagnosis of placenta accreta was 100% with ultrasound and 76.9% for MRI (P = 0.03). Specificity was 37.5% with ultrasonography and 50% for MRI (P = 0.6). The features of greatest sensitivity on ultrasonography were intraplacental lacunae and loss of the normal retroplacental clear space. Increased vascularization in the uterine serosa-bladder wall interface and vascularization perpendicular to the uterine wall had the best positive predictive value (92%). At MRI, uterine bulging had the best positive predictive value (85%) and its combination with the presence of dark intraplacental bands on T2-weighted images improved the predictive value to 90%. Conclusion: Ultrasound imaging is the mainstay of screening for placenta accreta. MRI appears to be complementary to ultrasonography, especially when there are few ultrasound signs. [ABSTRACT FROM AUTHOR]

Background. The genotoxicity of zidovudine has been established in experimental models. The objective of the study was to identify genotoxicity markers in cord blood cells from newborns exposed in utero to antiretroviral (ARV) combinations containing zidovudine.Methods. Cells were investigated by karyotyping and gene expression analysis of the CD34+ hematopoietic stem/progenitor cell (HPC) compartment.Results. Karyotyping of the cord blood cells from 15 ARV-exposed newborns and 12 controls revealed a higher proportion of aneuploid cells in the exposed group (median, 18.8% [interquartile range, 10.0%–26.7%] vs 6.6% [interquartile range, 3.1%–11.7%]; P < .001). All chromosomes were involved, with a random distribution of these alterations. Gene expression profiling of CD34+ HPCs from 7 ARV-exposed and 6 control newborns revealed that >300 genes were significantly upregulated or downregulated by at least 1.5-fold in the exposed group (P < .05 for all comparisons). Significant alterations of genes involved in cell cycle control, mitotic checkpoints, and DNA repair were identified. Although this study does not allow discrimination between the roles of each of the 3 drugs, both cytogenetic and transcriptional findings are similar to those in cellular experiments that used zidovudine alone.Conclusions. The cord blood cells, including hematopoietic stem cells, from newborns exposed in utero to a zidovudine-based ARV combination present cytogenetic and transcriptional abnormalities compatible with DNA damage. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the potential of 3-dimensional (3D) power Doppler imaging to predict neonatal outcome and pulmonary arterial hypertension (PAH) in congenital diaphragmatic hernia (CDH). Study design: In this prospective observational study, 3D-power Doppler ultrasonography was performed in 21 cases with isolated CDH between 23 and 33 weeks of gestation and in 58 controls between 20 and 40 weeks. Using the same preestablished settings for all cases, power Doppler was applied to each lung, and fetal lung volumes (FLV) were estimated using the rotational technique. The 3D power Doppler histogram was used to determine the vascular indices, which were plotted against gestational age and compared with neonatal outcome, PAH, gestational age, and FLV. Results: Fetal pulmonary vascular indices showed a constant distribution throughout gestation, being significantly lower in cases with CDH than in controls (P < .001). Among CDH cases, the vascular indices were significantly lower in fetuses who died (P < .05), and in fetuses with neonatal PAN (P < .05). The severity of neonatal PAH was also associated with a progressive reduction in prenatal vascular indices (P < .05). All vascular indices correlated with o/e-FLV, but not with gestational age. Conclusion: All vascular indices seem to be constant throughout gestation. In isolated CDH, perinatal outcome and postnatal PAH can be predicted using the vascular indices assessed by 3D power Doppler histogram. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the accuracy of the none-invasive prenatal determination of polymerase chain reaction (PCR)-based fetal RhD genotyping. Study design: A prospective case series was undertaken on all RhD-negative pregnant women presenting for genetic counseling in our prenatal diagnosis center from January 2001 until December 2002. Results were compared with serologic RhD typing of the newborns. Results: Among the 285 pregnant women who participated in the study, fetal RhD status could be determined for 283 patients. In 2 cases, the RhD-negative phenotype of the mother was not the result of a complete RHD gene deletion, and therefore, the status of the fetus could not be determined. Neither false-negative nor false-positive results were observed. Conclusion: The present report demonstrates that a reliable fetal RHD genotype determination can be achieved with 100% accuracy. It is therefore possible to consider that such an assay could be systematically proposed to all RhD-negative pregnant women in order to more effectively utilize RhD prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to determine whether the RhD gene is expressed in trophoblast at any stage of gestation.Study Design: Trophoblast and fetal tissue were obtained from 18 pregnancies at 8 to 40 weeks' gestation. Deoxyribonucleic acid and ribonucleic acid were extracted from trophoblast. Complementary deoxyribonucleic acid was synthesized from ribonucleic acid, and reverse transcriptase-polymerase chain reaction was performed using primers specific for the RhD gene. Deoxyribonucleic acid was extracted from fetal tissue to determine the fetal RhD status by means of polymerase chain reaction. Antigen expression was also sought by analytic cytometric analysis (flow cytometry and immunocytochemistry) using a monoclonal anti-D antibody.Results: Trophoblast was studied from various combinations of RhD-positive and RhD-negative fetuses (on deoxyribonucleic acid) from mothers to find no RhD gene expression in any sample. Flow cytometry and immunocytochemistry confirmed this by demonstrating no RhD antigen sites on trophoblast cells.Conclusion: Contrary to a previous report, we conclude that the RhD gene is not expressed in human trophoblast in any trimester. [ABSTRACT FROM AUTHOR]

Maternal 25-hydroxyvitamin D (25-OHD) deficiency during pregnancy may increase the risk of preterm and small-for-gestational age (SGA) birth, but studies report conflicting results. We used a multicenter prospective cohort of 2813 pregnant women assessed for 25-OHD levels in the first trimester of pregnancy to investigate the association between maternal 25-OHD concentrations and risks of preterm birth (<37 weeks) and SGA (birthweight <10th percentile). Odds ratios were adjusted (aOR) for potential cofounders overall and among women with light and dark skin separately, based on the Fitzpatrick scale. 25-OHD concentrations were <20 ng/mL for 45.1% of the cohort. A total of 6.7% of women had a preterm birth. The aOR for preterm birth associated with the 1st quartile of 25-OHD concentrations compared to the 4th quartile was 1.53 (95% confidence interval (CI): 0.97–2.43). In stratified analyses, an association was observed for women with darker skin (aOR = 2.89 (95% CI: 1.02–8.18)), and no association with lighter skin. A total of 11.9% of births were SGA and there was no association overall or by skin color. Our results do not provide support for an association between maternal first trimester 25-OHD deficiency and risk of preterm or SGA birth overall; the association with preterm birth risk among women with darker skin requires further investigation. [ABSTRACT FROM AUTHOR]

* Context.--SARS-CoV-2 can undergo maternal--fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. Objective.--To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.--Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2--infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. Results.--Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.--SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement. [ABSTRACT FROM AUTHOR]

* Context.--The number of neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasing, and in a few there are reports of intrauterine infection. Objective.--To characterize the placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection. Design.--Case-based retrospective analysis by a multinational group of 19 perinatal specialists of the placental pathology findings from 2 cohorts of infants delivered to mothers testing positive for SARS-CoV-2: live-born neonates infected via transplacental transmission who tested positive for SARS-CoV-2 after delivery and had SARS-CoV-2 identified in cells of the placental fetal compartment by molecular pathology, and stillborn infants with syncytiotrophoblast positive for SARS-CoV-2. Results.--In placentas from all 6 live-born neonates acquiring SARS-CoV-2 via transplacental transmission, the syncytiotrophoblast was positive for coronavirus using immunohistochemistry, RNA in situ hybridization, or both. All 6 placentas had chronic histiocytic intervillositis and necrosis of the syncytiotrophoblast. The 5 stillborn/terminated infants had placental pathology findings that were similar, including SARS-CoV-2 infection of the syncytiotrophoblast, chronic histiocytic intervillositis, and syncytiotrophoblast necrosis. Conclusions.--Chronic histiocytic intervillositis together with syncytiotrophoblast necrosis accompanies SARS-CoV-2 infection of syncytiotrophoblast in live-born and stillborn infants. The coexistence of these 2 findings in all placentas from live-born infants acquiring their infection prior to delivery indicates that they constitute a pathology risk factor for transplacental fetal infection. Potential mechanisms of infection of the placenta and fetus with SARSCoV-2, and potential future studies, are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Serum calcium rapidly declines at birth because of the sudden interruption of the maternal-fetal calcium influx. Several factors are known to influence serum calcium in the first days of life, including circulating concentrations of maternal vitamin D. Objective was to establish the normal range variations of neonatal serum calcium according to the current French vitamin D supplementation during pregnancy, i.e., 100,000 IU of cholecalciferol during the third trimester. Methods: We included in our prospective cohort study 1,002 mother-newborn dyads recruited from April 2012 to July 2014 in two centers located in the neighborhoods of Paris, France. Results: Total serum calcium at 3 days of life in neonates varied from 2.06 mmol/L to 2.73 mmol/L [2.5 and 97.5 percentiles], with a mean of 2.45 mmol/L. Serum calcium was similar between babies born from vitamin D-supplemented mothers and those born from non-supplemented ones. In univariate and multivariable analyses, we demonstrated the importance of maternal and cord blood 25(OH)D concentrations for newborn serum calcium maintenance. Conclusion: We established that the expected serum calcium in neonates ranges between 2.06 mmol/L and 2.73 mmol/L which is significantly wider than the adult range. This finding should help physicians in the diagnosis of hypo- or hypercalcemia. In addition, our study supports the importance of vitamin D supplementation and 25(OH)D status for neonatal serum calcium maintenance. [ABSTRACT FROM AUTHOR]

Severe infections during pregnancy and postpartum are rare, despite a high frequency of bacteraemia, but remain on of the leading cause of maternal death. Therapeutic guidelines validated in general population should be applied to pregnant women, with regards to their specificities: insidious clinical signs and rapid onset, clinical presentation often as respiratory failure due to physiological changes during pregnancy; most frequent causes: pneumonia, pyelonephritis, genitary tract infections; sensibility to virus, Listeria, malaria, due to immunological changes during pregnancy; caesarean section is the single most important risk factor of postpartum infection; aggressive treatment should be started promptly, including fluid infusion and early administration of vasoactive agents (Norepinephrine); broad-spectrum intravenous empirical antibiotic therapy must be established immediately (within the first hour), and chosen according to frequent microorganisms involved in sepsis during pregnancy; infectious source, mostly pelvic, is often accessible to surgery; if foetal extraction does not improve maternal outcomes, it remains necessary for obstetrical or foetal reasons and mandatory if chorioamnionitis is confirmed; specific attention should be drawn to streptococcus A invasive infection which experiments a recent resurgence and is correlated to a high morbidity and mortality for both the mother and the foetus; protocols should be written in every maternity. [ABSTRACT FROM AUTHOR]

Objectives: The sonographic features of endometriomas and their natural history during pregnancy remain poorly known. The objective of our study was to report our experience concerning the diagnosis, spontaneous progression and management of endometriomas during pregnancy.Study Design: A retrospective observational study in 46 patients (53 cysts) presenting with an ovarian endometrioma diagnosed during ultrasound examination at the first trimester of pregnancy. Sonographic findings (according to the criteria of the International Ovarian Tumor Analysis (IOTA) group and how they changed for each cyst during pregnancy and postpartum were reviewed, together with cyst management. The median follow-up was 4 years [IQR: 3-6]. Median age at diagnosis was 31 years [IQR: 27-35].Results: Among the 53 cysts identified as "endometriomas" on the first-trimester ultrasound examination, 49 (92%) were described like "cyst fluid with ground-glass echogenicity". Fifty-two cysts (98%) had a maximum diameter<100mm, only one cyst (2%) presented papillary projection and 5 cysts (9%) were multiloculated. During the second-trimester ultrasound monitoring of these cysts, of the 33 cysts that we monitored, 8 (24%) increased in size, 11 (34%) decreased in size, 5 (15%) disappeared and 9 (27%) did not change. During the third-trimester ultrasound monitoring of these cysts, of the 13 cysts that we monitored, 5 (39%) increased in size, 5 (39%) decreased in size, 2 (15%) disappeared and 1 (7%) did not change. All children (48 newborns) were born alive at a median gestational age of 39 weeks [IQR=39-40]. Only 10 cysts (19%) required surgical treatment. In all cases, surgery consisted of cystectomy. Two cysts were operated on during pregnancy (between 14 and 17 weeks of gestation) because of symptoms of adnexal torsion, 3 during cesarean section, and 5 postpartum. Four of the 10 (40%) cysts operated on were histopathologically "endometriomas", and one of them was decidualized. Four cysts were mucinous cystadenomas, one was a serous cystadenoma and one cyst was a dermoid cyst.Conclusion: This study underscores the difficulty of diagnosing endometriomas during pregnancy and the absolute necessity of surgical removal when ultrasonographic findings are doubtful. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to determine the value of maternal serum Down syndrome screening in patients affected by renal disease. Study Design: A study group of 54 pregnant women with renal diseases defined before pregnancy, was compared with a control group of 108 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal serum markers (free β-human chorionic gonadotropin [hCG], total hCG, alpha-fetoprotein) expressed in multiple of median and maternal renal function markers (creatinine, β2-microglobulin, α1-microglobulin) were assayed. Results: The percentage of patients in the Down syndrome at-risk group (>1:250) using free β-hCG was significantly higher (P < .02) in the renal disease group (48%) than in the control group (12%). No significant difference was observed for total hCG (25% vs 15%). Conclusion: Down syndrome screening using free β-hCG is not applicable in patients with renal disease whatever the maternal serum creatinine and can be used with caution when total hCG is used. [Copyright &y& Elsevier]

Objective: To estimate the prevalence and indications of terminations of pregnancy (TOP) between 22+0 and 31+6 weeks of gestational age in France and to examine the characteristics of women by indication of TOP.Study Design: From the EPIPAGE 2 population-based cohort study of preterm births in France in 2011, we selected 5009 singleton live births, stillbirths and TOP that occurred between 22 and 31 weeks. We estimated the proportion of TOP by gestational age. We then classified terminations by indications into 4 categories: fetal anomalies (TOPFA), preterm premature rupture of the membranes (PPROM), maternal conditions and fetal growth restriction (FGR). We also classified TOPFA by type of anomaly. Maternal characteristics were compared between TOPFA and TOP for maternal or fetal conditions without congenital anomaly.Results: 23.1% of all births and 54.3% of stillbirths were terminations. The proportion of terminations was 36.9% of all births at 22 weeks, 50.2% at 24 weeks and <10% at 30-31 weeks. 85.8% of terminations were for fetal anomaly, 4.4% for PPROM, 6.1% for maternal complications and 3.7% for severe FGR. Compared to women with a TOPFA, those with a termination for maternal or fetal conditions were more often nulliparous, single, African, obese, smokers and covered by non-standard insurance for women in socially deprived circumstances.Conclusion: In France, there is a high proportion of TOP of which 14% are for indications other than congenital anomalies. Because rates of terminations have an impact on very preterm birth and perinatal mortality rates, studies on pregnancy outcome should report all terminations, not only those for congenital anomalies. [ABSTRACT FROM AUTHOR]

The measurement of calcitriol [1,25(OH 2 )D], is important for the differential diagnosis of several disorders of calcium/phosphorus metabolism but is time-consuming and tricky. We measured serum calcitriol with a new automated direct assay on the Liaison XL platform in 888 healthy French Caucasian subjects aged 18–89 years, 32 patients with a surgically-proven PHPT, 32 pregnant women at the end of the first and at the end of the third trimester, and 24 dialysis patients before and after one year of supplementation with vitamin D3 or placebo. The mean calcitriol concentration (± SD) in the healthy population was 52.9 ± 14.5 ng/L with a 95% CI interval of 29–83.6 ng/L. In PHPT patients, calcitriol concentration was 81.6 ± 29.0 ng/L, 15 of them (46.9%) having a concentration > 83.6 ng/L. In pregnant women, calcitriol was 80.4 ± 26.4 ng/L at the end of the first trimester, and 113.1 ± 33.0 ng/L at the end of the third trimester, 12 (37.5%) and 26 (81.3%) of them having a calcitriol concentration > 83.6 ng/L at the first and third trimesters respectively. In 14 dialysis patients, calcitriol was 9.5 ± 7.7 ng/L and rose to 19.3 ng/L after one year of supplementation with 50,000 IU vitamin D3/month. In 10 other dialysis patients, calcitriol was 9.9 ± 2.9 ng/L and remained stable (12.4 ± 3.7 ng/L) after one year of placebo. In conclusion, this new automated calcitriol assay, in addition to presenting excellent analytical performances, gives the expected variations in patients compared to “normal” values obtained in an extensive reference population. [ABSTRACT FROM AUTHOR]