Neuropathological hallmarks of antenatal mitochondrial diseases with a corpus callosum defect.

Corpus callosum defects are frequent congenital cerebral disorders caused by mutations in more than 300 genes. These include genes implicated in corpus callosum development or function, as well as genes essential for mitochondrial physiology. However, in utero corpus callosum anomalies rarely raise a suspicion of mitochondrial disease and are characterized by a very large clinical heterogeneity. Here, we report a detailed pathological and neuro-histopathological investigation of nine foetuses from four unrelated families with prenatal onset of corpus callosum anomalies, sometimes associated with other cerebral or extra-cerebral defects. Next generation sequencing allowed the identification of novel pathogenic variants in three different nuclear genes previously reported in mitochondrial diseases: TIMMDC1, encoding a Complex I assembly factor never involved before in corpus callosum defect; MRPS22, a protein of the small mitoribosomal subunit; and EARS2, the mitochondrial tRNA-glutamyl synthetase. The present report describes the antenatal histopathological findings in mitochondrial diseases and expands the genetic spectrum of antenatal corpus callosum anomalies establishing OXPHOS function as an important factor for corpus callosum biogenesis. We propose that, when observed, antenatal corpus callosum anomalies should raise suspicion of mitochondrial disease and prenatal genetic counselling should be considered.

Prenatal diagnosis of isolated bilateral clubfoot: Is amniocentesis indicated?

INTRODUCTION: The aim of this study is to evaluate the benefit of cytogenetic testing by amniocentesis after an ultrasound diagnosis of isolated bilateral talipes equinovarus. MATERIAL AND METHODS: This multicenter observational retrospective study includes all prenatally diagnosed cases of isolated bilateral talipes equinovarus in five fetal medicine centers from 2012 through 2021. Ultrasound data, amniocentesis results, biochemical analyses of amniotic fluid and parental blood samples to test neuromuscular diseases, pregnancy outcomes, and postnatal outcomes were collected for each patient. RESULTS: In all, 214 fetuses with isolated bilateral talipes equinovarus were analyzed. A first-degree family history of talipes equinovarus existed in 9.8% (21/214) of our cohort. Amniocentesis was proposed to 86.0% (184/214) and performed in 70.1% (129/184) of cases. Of the 184 karyotypes performed, two (1.6%) were abnormal (one trisomy 21 and one triple X syndrome). Of the 103 microarrays performed, two (1.9%) revealed a pathogenic copy number variation (one with a de novo 18p deletion and one with a de novo 22q11.2 deletion) (DiGeorge syndrome). Neuromuscular diseases (spinal muscular amyotrophy, myasthenia gravis, and Steinert disease) were tested for in 56 fetuses (27.6%); all were negative. Overall, 97.6% (165/169) of fetuses were live-born, and the diagnosis of isolated bilateral talipes equinovarus was confirmed for 98.6% (139/141). Three medical terminations of pregnancy were performed (for the fetuses diagnosed with Down syndrome, DiGeorge syndrome, and the 18p deletion). Telephone calls (at a mean follow-up age of 4.5 years) were made to all parents to collect medium-term and long-term follow-up information, and 70 (33.0%) families were successfully contacted. Two reported a rare genetic disease diagnosed postnatally (one primary microcephaly and one infantile glycine encephalopathy). Parents did not report any noticeably abnormal psychomotor development among the other children during this data collection. CONCLUSIONS: Despite the low rate of pathogenic chromosomal abnormalities diagnosed prenatally after this ultrasound diagnosis, the risk of chromosomal aberration exceeds the risks of amniocentesis. These data may be helpful in prenatal counseling situations.

Biochemical Screening for Fetal Trisomy 21: Pathophysiology of Maternal Serum Markers and Involvement of the Placenta.

It is now well established that maternal serum markers are often abnormal in fetal trisomy 21. Their determination is recommended for prenatal screening and pregnancy follow-up. However, mechanisms leading to abnormal maternal serum levels of such markers are still debated. Our objective was to help clinicians and scientists unravel the pathophysiology of these markers via a review of the main studies published in this field, both in vivo and in vitro, focusing on the six most widely used markers (hCG, its free subunit hCGß, PAPP-A, AFP, uE3, and inhibin A) as well as cell-free feto-placental DNA. Analysis of the literature shows that mechanisms underlying each marker's regulation are multiple and not necessarily directly linked with the supernumerary chromosome 21. The crucial involvement of the placenta is also highlighted, which could be defective in one or several of its functions (turnover and apoptosis, endocrine production, and feto-maternal exchanges and transfer). These defects were neither constant nor specific for trisomy 21, and might be more or less pronounced, reflecting a high variability in placental immaturity and alteration. This explains why maternal serum markers can lack both specificity and sensitivity, and are thus restricted to screening.

Neonatal Morbidity of Monoamniotic Twin Pregnancies: A Systematic Review and Meta-analysis.

OBJECTIVE: This study was aimed to report the incidence of neonatal morbidity in monochorionic monoamniotic (MCMA) twin pregnancies according to gestational age at birth and type of management adopted (inpatient or outpatient). STUDY DESIGN: Medline and Embase databases were searched. Inclusion criteria were nonanomalous MCMA twins. The primary outcome was a composite score of neonatal morbidity, defined as the occurrence of at least one of the following outcomes: respiratory morbidity, overall neurological morbidity, severe neurological morbidity, and infectious morbidity, necrotizing enterocolitis at different gestational age windows (24-30, 31-32, 33-34, and 35-36 weeks). Secondary outcomes were the individual components of the primary outcome and admission to neonatal intensive care unit (NICU). Subanalysis according to the type of surveillance strategy (inpatient compared with outpatient) was also performed. Random effect meta-analyses were used to analyze the data. RESULTS: A total of 14 studies including 685 MCMA twin pregnancies without fetal anomalies were included. At 24 to 30, 31 to 32, 33 to 34, and 35 to 36 weeks of gestation, the rate of composite morbidity was 75.4, 65.5, 37.6, and 18.5%, respectively, the rate of respiratory morbidity was 74.2, 59.1, 35.5, and 12.2%, respectively, while overall neurological morbidity occurred in 15.3, 10.2, 4.3, and 0% of the cases, respectively. Infectious morbidity complicated 13, 4.2, 3.1, and 0% of newborns while 92.1, 81.6, 58.7, and 0% of cases required admission to NICU. Morbidity in pregnancies delivered between 35 and 36 weeks of gestation was affected by the very small sample size of cases included. When comparing the occurrence of overall morbidity according to the type of management (inpatient or outpatient), there was no difference between the two surveillance strategies (p = 0.114). CONCLUSION: MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity that gradually decreases with increasing gestational age at delivery with a significant reduction for pregnancies delivered between 33 and 34 weeks. We found no difference in the occurrence of neonatal morbidity between pregnancies managed as inpatient or outpatient. KEY POINTS: · MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity.. · Neonatal morbidity gradually decreases with increasing GA at delivery, mostly between 33 and 34 weeks.. · There is no difference in the occurrence of neonatal morbidity between in- or outpatient management..

Persistence of group B Streptococcus vaginal colonization and prevalence of hypervirulent CC-17 clone correlate with the country of birth: a prospective 3-month follow-up cohort study.

To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.

Does women's place of birth affect their opportunity for an informed choice about Down syndrome screening? A population-based study in France.

BACKGROUND: To examine disparities by maternal place of birth in the opportunity to make an informed choice about Down syndrome screening, in France, where the national guidelines recommend that physicians offer it to all pregnant women. METHODS: We used population-based data from the nationally representative French Perinatal Surveys in 2010 and 2016 (N=24,644 women) to analyze the opportunity for an informed choice for prenatal screening, measured by a composite indicator. RESULTS: Among the 24 644 women in the study, 20 612 (83.6%) were born in France, 861 (3.5%) elsewhere in Europe, 1550 (6.3%) in North Africa, and 960 (3.9%) in sub-Saharan Africa. The probability of screening was lower for women born outside France. After adjustment for survey year, maternal age, parity, education level, and the maternity unit's level of perinatal care, women born outside France had the opportunity to make an informed choice less often than women born in France. This association remained essentially the same even after excluding women without adequate prenatal care. CONCLUSIONS: Women born outside France, including those with adequate prenatal care, had less opportunity than women born in France to make an informed choice about prenatal screening for Down syndrome.

Risk Factors for Infant Colonization by Hypervirulent CC17 Group B Streptococcus: Toward the Understanding of Late-onset Disease.

BACKGROUND: In infants, the mode of acquisition of CC17 group B Streptococcus (GBS), the hypervirulent clone responsible for late-onset disease (LOD), remains elusive. METHODS: In a prospective multicenter study in France, we evaluated GBS colonization in mother-baby pairs with 2 months of follow-up between 2012 and 2015. Criteria included positivity for GBS colonization at antenatal screening or at delivery. Maternal vaginal samples and infant oral cavity and stool samples were analyzed at delivery, 21 ± 7 days (D21), and 60 ± 7 days (D60) post-delivery. RESULTS: A total of 890 mother-baby pairs were analyzed. GBS colonized 7%, 21%, and 23% of the infants at birth, D21, and D60, respectively, of which 10%, 11%, and 13% were identified as CC17 GBS. Concordance between maternal and infant GBS type was 96%. At D21, the main risk factors for infant colonization by GBS were simultaneous maternal colonization of the vagina (odds ratio [OR], 4.50; 95% confidence interval [CI], 1.69-15.61) and breast milk (OR, 7.93; 95% CI, 3.81-17.14). Importantly, 38% (95% CI, 23%-56%) of infants colonized by CC17 GBS appeared colonized for the first time at D60 vs 18% (95% CI, 14%-24%; P < .049) of infants colonized by non-CC17 GBS. Multivariate analysis showed a higher risk for de novo infant colonization by CC17 at D60 than by other GBS (OR, 2.45; 95% CI, 1.02-5.88). CONCLUSIONS: The high incidence of CC17 GBS in LOD is likely due to an enhanced post-delivery mother-to-infant transmission.

Lack of consensus in the choice of termination of pregnancy for Turner syndrome in France.

BACKGROUND: The observed rate of termination of pregnancy (TOP) for Turner syndrome varies worldwide and even within countries. In this vignette study we quantified agreement among ten multidisciplinary prenatal diagnosis centers in Paris. METHODS: We submitted online three cases of Turner syndrome (increased nuchal translucency, normal ultrasound, aortic coarctation) to fetal medicine experts: one obstetrician, one pediatrician and one geneticist in each of the ten Parisian centers. Each case was presented in the form of a progressive clinical history with conditional links dependent upon responses. The background to each case was provided, along with the medical history of the parents and the counseling they got from medical staff. The experts indicated online whether or not they would accept the parents' request for TOP. We assessed the percentage of agreement for acceptance or refusal of TOP. We also used a multilevel logistic regression model to evaluate differences among obstetrician-gynecologists, pediatricians and cytogeneticists. RESULTS: Overall agreement among the experts to accept or refuse TOP was, respectively, 25 and 28%. The percentage of disagreement was 47%. The percentage of agreement to accept TOP was 33, 8 and 33% for obstetrician-gynecologists, pediatricians and cytogeneticists, respectively. The respective percentages of agreement to refuse TOP were 19, 47 and 26%. CONCLUSION: Our results show the lack of consensus with regard to decisions related to termination of pregnancy for Turner Syndrome. This lack of consensus in turn underscores the importance of multidisciplinary management of these pregnancies in specialized fetal medicine centers.

Non-invasive prenatal diagnosis of paternally inherited disorders from maternal plasma: detection of NF1 and CFTR mutations using droplet digital PCR.

BACKGROUND: To limit risks of miscarriages associated with invasive procedures of current prenatal diagnosis practice, we aim to develop a personalized medicine-based protocol for non-invasive prenatal diagnosis (NIPD) of monogenic disorders relying on the detection of paternally inherited mutations in maternal blood using droplet digital PCR (ddPCR). METHODS: This study included four couples at risk of transmitting paternal neurofibromatosis type 1 (NF1) mutations and four couples at risk of transmitting compound heterozygous CFTR mutations. NIPD was performed between 8 and 15 weeks of gestation, in parallel to conventional invasive diagnosis. We designed specific hydrolysis probes to detect the paternal mutation and to assess the presence of cell-free fetal DNA by ddPCR. Analytical performances of each assay were determined from paternal sample, an then fetal genotype was inferred from maternal plasma sample. RESULTS: Presence or absence of the paternal mutant allele was correctly determined in all the studied plasma DNA samples. CONCLUSIONS: We report an NIPD protocol suitable for implementation in an experienced laboratory of molecular genetics. Our proof-of-principle results point out a high accuracy for early detection of paternal NF1 and CFTR mutations in cell-free DNA, and open new perspectives for extending the technology to NIPD of many other monogenic diseases.

Comparison of the Induction-to-Delivery Interval in Terminations of Pregnancy with or without Dilapan-S®.

OBJECTIVE: In France, terminations of pregnancy (TOP) for medical reasons beyond the second trimester use mifepristone and misoprostol. We sought to determine the effectiveness of Dilapan-S®, an osmotic cervical dilator, in shortening the induction-to-delivery interval (IDI). MATERIALS AND METHODS: This retrospective study of TOP in 2010-2012 compared the results from 2 hospitals with different TOP protocols starting at 16 weeks' gestation, one (164 women) with and one (106) without Dilapan-S®. The principal endpoint was the IDI. Results were analyzed according to 2 definitions of induction onset: definition 1, first dose of misoprostol in both centers, or definition 2, dilator placement if used, and otherwise first dose of misoprostol. RESULTS: With definition 1, the IDI was shorter with dilators (5 h 48 min vs. 10 h 18 min, p < 0.001); the rates of uterine evacuation within 12 and 24 h were higher (94.5 and 100 vs. 68.9 and 91.5%, p < 0.001), and the time between first misoprostol dose and amniotomy was shorter (0 h 47 min vs. 4 h 30 min, p < 0.001). Under definition 2, the IDI was longer with dilators (18 h 24 min vs. 10 h 18 min, p < 0.001), but the rate of evacuation within 24 h did not differ significantly. CONCLUSION: Dilapan-S® acts on cervical ripening and dilatation, thereby allowing early amniotomy. Assessing potential side effects and women's satisfaction requires prospective trials.

Droplet digital PCR combined with minisequencing, a new approach to analyze fetal DNA from maternal blood: application to the non-invasive prenatal diagnosis of achondroplasia.

BACKGROUND: Achondroplasia is generally detected by abnormal prenatal ultrasound findings in the third trimester of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained by aspiration of amniotic fluid. This invasive procedure presents a small but significant risk for both the fetus and mother. Therefore, non-invasive procedures using cell-free fetal DNA in maternal plasma have been developed for the detection of the fetal achondroplasia mutations. METHODS: To determine whether the fetus carries the de novo mis-sense genetic mutation at nucleotide 1138 in FGFR3 gene involved in >99% of achondroplasia cases, we developed two independent methods: digital-droplet PCR combined with minisequencing, which are very sensitive methods allowing detection of rare alleles. RESULTS: We collected 26 plasmatic samples from women carrying fetus at risk of achondroplasia and diagnosed to date a total of five affected fetuses in maternal blood. The sensitivity and specificity of our test are respectively 100% [95% confidence interval, 56.6-100%] and 100% [95% confidence interval, 84.5-100%]. CONCLUSIONS: This novel, original strategy for non-invasive prenatal diagnosis of achondroplasia is suitable for implementation in routine clinical testing and allows considering extending the applications of these technologies in non-invasive prenatal diagnosis of many other monogenic diseases. © 2016 John Wiley & Sons, Ltd.

Prevalence of COVID-19 among pregnant women and its impact on childbirth in March 2021: Data from the French National Perinatal Survey.

BACKGROUND: Several series reported obstetric complications among pregnant women hospitalized for COVID. These data, because they focused on women with the most severe presentations or with specific immunosuppression, were likely to overestimate the risks associated with the infection at a global level. To date, population-based studies, most of which collected data from registers of women hospitalized during pregnancy for COVID-19, remain sparse. Neither the prevalence of COVID-19 in pregnant women nor the overall extent of obstetric complications worldwide, compared with uninfected pregnant women is clear. The impact of COVID-19 on perinatal care and obstetric management is thus difficult to evaluate. OBJECTIVES: To evaluate the prevalence and determinants of COVID-19 diagnosis during pregnancy and assess related obstetric practices and perinatal outcomes. STUDY DESIGN: Used data collected at childbirth in France from women included in the 2021 national perinatal survey, we compared women with and without a COVID-19 diagnosis (for sociodemographic characteristics) and then women with no COVID-19 diagnosis during pregnancy, women diagnosed more than 15 days preceding childbirth, and those diagnosed within those 15 days for outcomes. RESULTS: The COVID-19 prevalence during pregnancy was 5.7 % (95 %CI 5.3-6.1) (678/11 930). The aOR for COVID-19 diagnosis associated with non-French nationality was 1.27 (95 %CI 1.03-1.58), with non-smoking 0.63 (95 %CI 0.55-0.81) and with multiparity 1.21 (95 %CI 1.02-1.45). Diagnosis occurred in the third trimester for 49 % -28.5 % in the 15 days before childbirth. Women with COVID-19 diagnosed during pregnancy had preterm births more often (9.6 %) than women without this diagnosis (6.9 %) (P = 0.007). Women with COVID-19 diagnosed within the 15 days preceding childbirth had more cesarean deliveries (28.3 %) than those diagnosed earlier (17.4 %) (P = 0.02). CONCLUSIONS: COVID-19 diagnosis during pregnancy was associated with an increased risk of preterm birth. Obstetric outcomes were poorer in women with a COVID-19 diagnosis in the 15 days preceding childbirth.

Usefulness of early morphological ultrasound in association with cell-free DNA testing in case of atypical serum markers in first trimester of pregnancy: A retrospective study over 5 years.

BACKGROUND: Early morphologic ultrasound, generally carried out in case of atypical first trimester serum markers (PAPP-A and/or free hCGß <0.30 MoM), has not been re-evaluated since the possibility of performing a cell-free fetal DNA analysis in this indication. Our objective was to evaluate the usefulness of early morphological ultrasound in case of atypical profile of serum markers performed in association with Non-Invasive Prenatal Testing (NIPT). METHODS: This was a single-center retrospective study in a tertiary maternity. Between January 2017 and December 2021, women with an atypical first trimester serum markers and low/intermediate risk for trisomy 21 (<1/50) were included. The clinical data, results of first trimester serum markers, NIPT, early morphological ultrasound and subsequent ultrasounds and other investigations (amniocentesis, pregnancy outcomes) were analyzed. RESULTS: After exclusion of women with high-risk of trisomy 21 and lost to follow-up, 163 women were included. In 72 % of cases (117/163), women had a low risk of trisomy 21, and 39 % (59/163) had an early morphological ultrasound. Early morphological ultrasound was useful to detect severe IUGR leading to the suspicion of triploidy (3/163, 1.8 %). In all other situations, it did not allow earlier management. After analysis of the 3 triploidy cases, a collapsed profile for both serum markers was demonstrated (<0.25 MoM). CONCLUSIONS: Systematic early morphological ultrasound in case of an atypical serum marker profile seems useless considering the performance of NIPT. An ultrasound restricted to women with both markers below 0.25 MoM would allow the early detection of triploidy.

[Fetal death: Expert consensus from the College of French Gynecologists and Obstetricians]. / Mort fœtale : consensus formalisé d'experts du Collège national des gynécologues et obstétriciens français.

Fetal death is defined as the spontaneous cessation of cardiac activity after fourteen weeks of amenorrhea. In France, the prevalence of fetal death after 22 weeks is between 3.2 and 4.4/1000 births. Regarding the prevention of fetal death in the general population, it is not recommended to counsel for rest and not to prescribe vitamin A, vitamin D nor micronutrient supplementation for the sole purpose of reducing the risk of fetal death (Weak recommendations; Low quality of evidence). It is not recommended to prescribe aspirin (Weak recommendation; Very low quality of evidence). It is recommended to offer vaccination against influenza in epidemic periods and against SARS-CoV-2 (Strong recommendations; Low quality of evidence). It is not recommended to systematically look for nuchal cord encirclements during prenatal screening ultrasounds (Strong Recommendation; Low Quality of Evidence) and not to perform systematic antepartum monitoring by cardiotocography (Weak Recommendation; Very Low Quality of Evidence). It is not recommended to ask women to perform an active fetal movement count to reduce the risk of fetal death (Strong Recommendation; High Quality of Evidence). Regarding evaluation in the event of fetal death, it is suggested that an external fetal examination be systematically offered (Expert opinion). It is recommended that a fetopathological and anatomopathological examination of the placenta be carried out to participate in cause identification (Strong Recommendation. Moderate quality of evidence). It is recommended that chromosomal analysis by microarray testing be performed rather than conventional karyotype, in order to be able to identify a potentially causal anomaly more frequently (Strong Recommendation, moderate quality of evidence); to this end, it is suggested that postnatal sampling of the placental fetal surface for genetic purposes be preferred (Expert Opinion). It is suggested to test for antiphospholipid antibodies and systematically perform a Kleihauer test and a test for irregular agglutinins (Expert opinion). It is suggested to offer a summary consultation, with the aim of assessing the physical and psychological status of the parents, reporting the results, discussing the cause and providing information on monitoring for a subsequent pregnancy (Expert opinion). Regarding announcement and support, it is suggested to announce fetal death without ambiguity, using simple words and adapting to each situation, and then to support couples with empathy in the various stages of their care (Expert opinion). Regarding management, it is suggested that, in the absence of a situation at risk of disseminated intravascular coagulation or maternal vitality, the patient's wishes should be taken into account when determining the time between the diagnosis of fetal death and induction of birth. Returning home is possible if it's the patient wish (Expert opinion). In all situations excluding maternal life-threatening emergencies, the preferred mode of delivery is vaginal delivery, regardless the history of cesarean section(s) history (Expert opinion). In the event of fetal death, it is recommended that mifepristone 200mg be prescribed at least 24hours before induction, to reduce the delay between induction and delivery (Low recommendation. Low quality of evidence). There are insufficient data in the literature to make a recommendation regarding the route of administration (vaginal or oral) of misoprostol, neither the type of prostaglandin to reduce induction-delivery time or maternal morbidity. It is suggested that perimedullary analgesia be introduced at the start of induction if the patient asks, regardless of gestational age. It is suggested to prescribe cabergoline immediately in the postpartum period in order to avoid lactation, whatever the gestational age, after discussing the side effects of the treatment with the patient (Expert opinion). The risk of recurrence of fetal death after unexplained fetal death does not appear to be increased in subsequent pregnancies, and data from the literature are insufficient to make a recommendation on the prescription of aspirin. In the event of a history of fetal death due to vascular issues, low-dose aspirin is recommended to reduce perinatal morbidity, and should not be combined with heparin therapy (Low recommendation, very low quality of evidence). It is suggested not to recommend an optimal delay before initiating another pregnancy just because of the history of fetal death. It is suggested that the woman and co-parent be informed of the possibility of psychological support. Fetal heart rate monitoring is not indicated solely because of a history of fetal death. It is suggested that delivery not be systematically induced. However, induction can be considered depending on the context and parental request. The gestational age will be discussed, taking into account the benefits and risks, especially before 39 weeks. If a cause of fetal death is identified, management will be adapted on a case-by-case basis (expert opinion). In the event of fetal death occurring in a twin pregnancy, it is suggested that the surviving twin be evaluated as soon as the diagnosis of fetal death is made. In the case of dichorionic pregnancy, it is suggested to offer ultrasound monitoring on a monthly basis. It is suggested not to deliver prematurely following fetal death of a twin. If fetal death occurs in a monochorionic twin pregnancy, it is suggested to contact the referral competence center, in order to urgently look for signs of acute fetal anemia on ultrasound in the surviving twin, and to carry out weekly ultrasound monitoring for the first month. It is suggested not to induce birth immediately.

Perinatal survival among very preterm singletons born after detection of early-onset fetal growth restriction with or without maternal hypertensive disorders: A population-based study in France.

OBJECTIVE: To investigate the management and survival of very preterm singletons born because of fetal growth restriction (FGR) with or without maternal hypertensive disorders in France. STUDY DESIGN: From a population-based cohort of very preterm births between 22 and 31 weeks in France in 2011, the study population included all non-anomalous singleton pregnancies delivered because of detected FGR with or without maternal hypertensive disorders. Antenatal detection of FGR was defined as an estimated fetal weight <10th percentile with or without fetal Doppler abnormalities or growth arrest. All fetuses were alive at the time of detection of FGR. Indicators of active perinatal management (antenatal steroids, pre-labor cesarean and birth in level 3 maternity unit) and fetal/neonatal outcomes (terminations of pregnancy (TOP), stillbirths, neonatal deaths and survival to discharge) were compared by gestational age between FGR associated with maternal hypertensive disorders and isolated FGR. RESULTS: Overall, 398 pregnancies delivered before 32 weeks for FGR associated with hypertensive disorders and 234 for isolated FGR. Active perinatal care was rare before 26 weeks in both groups and about one in five cases associated with maternal hypertensive disorders received steroids and was born by prelabor cesarean compared to none for isolated FGR. Before 25 weeks of gestation age, more pregnancies resulted in TOP when FGR was associated with hypertensive disorders compared to isolated FGR (respectively, 76.2 % vs 28.0 % at 22-23 weeks, P = 0.002 and 57.9 % vs 21.1 % at 24 weeks, P = 0.028) whereas stillbirths were more common among isolated FGR (respectively, 23.8 % vs 72.0 % at 22-23 weeks, P = 0.002 and 36.8 % vs 73.7 % at 24 weeks, P = 0.030). Survival to discharge was higher at any gestational age when the cause of birth was FGR associated with hypertensive disorders compared to isolated FGR. CONCLUSION: The management and pregnancy outcomes differed when FGR was associated with maternal hypertensive disorders or isolated. The proportion of TOP was higher when FGR was associated with hypertensive disorders and the proportion of stillbirths was higher in isolated FGR.

A dramatic fetal outcome following transplacental transfer of dasatinib.

Chronic myeloid leukemia is a chronic myeloproliferative disorder of hematopoietic stem cells that occurs in 10% of cases in women of childbearing age. Treatment is mainly based on tyrosine kinase inhibitors such as imatinib, dasatinib, or nilotinib. However, the maternal and embryofetal safety of these drugs in pregnant women is poorly documented. Here, we report the case of a 23-year-old woman diagnosed with a chronic myeloid leukemia. She was treated with dasatinib while she was diagnosed as being pregnant at 7 weeks of gestation. Obstetric monitoring showed fetal hydrops associated with severe fetal bicytopenia, leading to termination of pregnancy at 16 weeks of gestation. Dasatinib concentrations were 4 ng/ml in maternal plasma (usual concentration), 3 ng/ml in fetal plasma, and 2 ng/ml in amniotic fluid. Fetal karyotype was normal. To our knowledge, this is the first report clearly quantifying the amount of transplacental transfer of dasatinib. Moreover, fetal hematological toxicity (leukopenia and thrombocytopenia), edema, ascites, and pleural effusions described in this case report are well-known side effects of dasatinib in adults. Hence, this case highlights the imputability of dasatinib in this adverse outcome, and clearly questions its safety during pregnancy.

Meconium peritonitis in both fetuses with early twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin bloodflow through placental vascular anastomoses. We present a TTTS case treated with fetoscopic laser photocoagulation (FLP) that was complicated by perinatal meconium peritonitis in both twins. Ten weeks following laser treatment, the two fetuses showed intra-abdominal hyperechogenicity and ascites. After birth, the two newborns were surgically managed for peritonitis. We discuss the pathogenesis of this double insult. The present case highlights the role of end-circulation bowel thrombi as the potential cause of subsequent intestinal perforation.

[Factors Associated with Prolonged Duration of Labor in Medical Termination of Pregnancy in the 2nd and 3rd Trimesters]. / Facteurs associés à une durée de travail prolongée en cas d'interruption médicale de grossesse aux 2e et 3e trimestres.

OBJECTIVE: In the context of a medical termination of pregnancy, prolonged labor may accentuate the difficulty of women's experience and increase the risk of associated complications. The factors associated with prolonged labor are not known. Reducing the duration of labor could limit these complications. Determining the relevant factors associated with prolonged labor defined as a delay between the onset of induction and delivery greater than or equal to 12hours and comparing the complications rates between the two groups. METHOD: We conducted a retrospective study at Port Royal Maternity Hospital from 2017 to 2019, including medical terminations of pregnancy by vaginal delivery in the 2nd and 3rd trimesters for fetal or maternal reasons. RESULTS: Two hundred twenty-seven patients were included and divided into two comparative groups based on the duration of labor: labor <12h (n=173) and labor ≥12h (n=54). The mean maternal age was 33.7 years. Forty-four percent of patients were nulliparous, 15.8 % had a history of cesarean section. The average gestational age was 20+2 weeks of gestation. The average duration of labor was 9.7hours. The duration of labor was greater than 24hours in 3% of cases (7/227). Advanced gestational age (22+3 vs. 20+5 p=0,04) and nulliparity (p=0.01) were associated with prolonged labor. Two other intermediate factors, not independent of the duration of labor, were significant: long time to rupture of membranes (239min vs. 427min p<0,01) and an unfavorable Bishop score at rupture (p=0,003). In both groups, the complications were placental retention and the occurrence of fever during labor. CONCLUSION: Two main factors affecting labor duration were identified in this study (term and nulliparity). This knowledge could allow women to be better informed about the expected time of labor and the potential associated risks.

Diagnostic value of fetal autopsy after early termination of pregnancy for fetal anomalies.

BACKGROUND: In early terminations of pregnancy for fetal anomaly (TOPFA) without identified cytogenetic abnormality, a fetal autopsy is recommended for diagnostic purposes, to guide genetic counseling. Medical induction, which allows analysis of a complete fetus, is generally preferred over surgical vacuum aspiration. Our objective was to assess the diagnostic value of fetal autopsies in these early terminations, relative to the first-trimester ultrasound, overall and by termination method. MATERIALS: For this retrospective study at the Port Royal Maternity Hospital, we identified all TOPFA performed from 11 weeks to 16 weeks diagnosed at the first-trimester ultrasound in cases with a normal karyotype. The principal endpoint was the additional value of the autopsy over /compared to the ultrasound and its impact on genetic counseling, globally and by termination method. The secondary objective was to compare the complication rate by method of termination. RESULTS: The study included 79 women during period of 2013-2017: 42 with terminations by medical induction and 37 by aspiration. Fetal autopsy found additional abnormalities in 54.4% of cases, more frequently after medical induction (77.5%) than after aspiration (21.4%, p < .01). Genetic counseling was modified in 20.6% of cases, more often after induction (32.5% vs 3.6%, p < .01). The length of stay was significantly longer and a secondary aspiration was required in 16,7% of case in the medical induction group (p < .01). CONCLUSION: Medically induced vaginal expulsion appears preferable and can change genetic counseling for subsequent pregnancies.

Implicit biases and differential perinatal care for migrant women: Methodological framework and study protocol of the BiP study part 3✰,✰✰.

BACKGROUND: The mechanisms of disparities in maternal and perinatal health between migrant and native women are multiple and remain poorly understood. Access to and quality of care are likely to participate in these mechanisms, and one hypothesis is the existence of implicit biases among caregivers through which ethno-racial belonging can influence medical decisions and consequently engender healthcare disparities. Their existence and their role in the generation of non-medically justified differential care have been documented in the United States apart from perinatal care, but remain largely unexplored in Europe. In this article, we present the study protocol and theoretical framework of a study that aims to test and quantify the existence of implicit bias toward African Sub-Saharan migrant women among caregivers working in the perinatal field, and to explore the association between implicit bias and differential care. MATERIAL AND METHODS: This study is based on an online survey to which French obstetricians, midwives, and anesthetists were invited to take part. The potential existence of implicit biases toward African Sub-Saharan migrant will be quantified through a validated tool, the Implicit Association Test. Then we will assess how implicit biases are likely to influence clinical decisions and lead to differential care using clinical vignettes designed by an experts group. DISCUSSION: Implicit bias and differential care are concept that are tricky to capture and interpret. This research program opens up in France a field of research on certain forms of health discriminations and sheds new light on the issue of social inequalities in perinatal health. STUDY REGISTRATION: Registration in the Open Science Framework portal: https://osf.io/djva7/?view_only=c6012ace3fe94165a65b05c2dc6aff9e.