Cell-free DNA screening for common autosomal trisomies using rolling-circle replication in twin pregnancies.

OBJECTIVE: To evaluate the performance of prenatal screening for common autosomal trisomies in twin pregnancies through the use of rolling-circle replication (RCR)-cfDNA as a first-tier test. METHOD: Prospective multicenter study. Women who underwent prenatal screening for trisomy (T) 21, 18 and 13 between January 2019 and March 2022 in twin pregnancies were included. Patients were included in two centers. The primary endpoint was the rate of no-call results in women who received prenatal screening for common autosomal trisomies by RCR-cfDNA at the first attempt, compared to that in prospectively collected samples from 16,382 singleton pregnancies. The secondary endpoints were the performance indices of the RCR-cfDNA. RESULTS: 862 twin pregnancies underwent screening for T21, T18 and T13 by RCR-cfDNA testing at 10-33 weeks' gestation. The RCR-cfDNA tests provided a no-call result from the first sample obtained from the patients in 107 (0.7%) singleton and 17 (2.0%) twin pregnancies. Multivariable regression analysis demonstrated that significant independent predictors of test failure were twin pregnancy and in vitro fertilization conception. All cases of T21 (n = 20/862; 2.3%), T18 (n = 4/862; 0.5%) and T13 (n = 1/862; 0.1%) were correctly detected by RCR-cfDNA (respectively, 20, 4 and 1 cases). Sensitivity was 100% (95% CI, 83.1%-100%), 100% (95% CI 39.8%-100%) and 100% (95% CI 2.5%-100%) for T21, T18 and T13, respectively, in twin pregnancies. CONCLUSION: The RCR-cfDNA test appears to have good accuracy with a low rate of no-call results in a cohort of twin pregnancies for the detection of the most frequent autosomal trisomies.

Neonatal herpes: case series in two obstetric centres over a 10-year period (2013-2023), France.

Neonatal herpes simplex virus (HSV) infection (HSV infection in infants less than 6 weeks of age) is rare but mortality and morbidity rates are high after disseminated disease and encephalitis. In France, the epidemiology is poorly described, and two decades ago, incidence was estimated to be 3 per 100,000 live births a year. We describe determinants, epidemiologic and clinical characteristics of neonatal HSV infection in a managed-care population attending in two major obstetric and paediatric centres, Paris, France, over a 10-year period. This retrospective case series study was conducted from 2013 to 2023, in infants less than 42 days of age who had virologically confirmed HSV infection. We report an overall rate of neonatal herpes of 5.5 per 100,000 live births a year and an incidence of symptomatic cases of 1.2 per 100,000 live births a year. HSV-1 was the major serotype involved (84.2%) and post-natal acquisition through the orolabial route reached 63.2%. All neonates who had neonatal HSV PCR screening (owing to clinical signs in parents) and who received prompt acyclovir treatment remained asymptomatic. Symptomatic forms accounted for 21.1% cases of the total and mortality was high (62.5% of symptomatic forms).   Conclusion: This case series confirms that neonates at risk for HSV disease and poor outcome are those born to HSV-seronegative mothers, preterm infants, and those who received acyclovir after onset of symptoms (mainly because mothers did not present evidence of acute HSV infection). Our study confirms the major role of HSV-1 and the frequency of its early post-natal acquisition. What is known: • Neonatal herpes simplex virus infection is rare but motality and morbidity rates are high after disseminted disease and encephalitis. National recommendations exist worldwide but mangement of this disease is not always easy. What is new: • As in France epidemiology of neonatal herpes is poorly described, our report is potentially an important addition to the existing literature. Moreover, we describe local practice that may be useful to physicians.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study.

BACKGROUND: Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. OBJECTIVE: To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination. STUDY DESIGN: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery. RESULTS: Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. CONCLUSION: Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required.

Performance of cell-free DNA testing for common fetal trisomies in triplet pregnancies.

OBJECTIVE: In singleton pregnancies, the use of cell-free DNA (cfDNA) analysis as a screening test for common fetal trisomies has spread worldwide though we still lack sufficient data for its use in triplet pregnancies. The objective of this study is to assess the performance of cfDNA testing in detecting fetal aneuploidies in triplet pregnancies as a first-tier test. METHOD: We performed a retrospective cohort study including data from pregnant women with a triplet pregnancy who underwent cfDNA testing between May 1, 2017, and January 15, 2020. cfDNA was obtained by massive parallel sequencing (VeriSeq NIPT solution; Illumina®). The objectives of the study were to assess the diagnostic performance of cfDNA testing for trisomy 21 (T21) (primary outcome), trisomy 18 (T18) and 13 (secondary outcomes). RESULTS: During the study period, cfDNA testing was performed in 255 women with triplet pregnancy, of which 165 (64.7%) had a neonatal outcome available. Three tests were positive for T21, one of which was confirmed by an antenatal karyotype, and the other was confirmed at birth. The third case did not undergo an invasive procedure and was not confirmed at birth (false positive). In one case, cfDNA testing was positive for T18 and was confirmed by an antenatal karyotype. There were no cases of trisomy 13 in the cohort. The no-call rate was 2.4% at first sampling. Fifty-eight (22.7%) women had embryo reduction, which in 40 (69%) of whom was performed after the cfDNA test result. CONCLUSION: cfDNA testing could be offered as primary screening for main fetal aneuploidies in triplet pregnancies after provision of appropriate patient information.

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

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

European reference network for rare inherited congenital anomalies (ERNICA) evidence based guideline on the management of gastroschisis.

BACKGROUND: The European Reference Network for rare Inherited Congenital Anomalies, ERNICA, guidelines for gastroschisis cover perinatal period to help teams to improve care. METHOD: A systematic literature search including 136 publications was conducted. Research findings were assessed following the GRADE methodology. The evidence to decision framework was used to determine the strength and direction of recommendations. RESULTS: The mode or timing of delivery do not impact neonatal mortality, risk of NEC or time on parenteral nutrition (PN). Intra or extra abdominal bowel dilatation predict complex gastroschisis and longer length of hospital stay but not increased perinatal mortality. Outcomes after Bianchi procedure and primary fascia closure under anesthesia are similar. Sutureless closure decreases the rate of surgical site infections and duration of ventilation compared to surgical closure. Silo-staged closure with or without intubation results in similar outcomes. Outcomes of complex gastroschisis (CG) undergoing early or delayed surgical repair are similar. Early enteral feeds starting within 14 days is associated with lower risk of surgical site infection. RECOMMENDATIONS: The panel suggests vaginal birth between 37 and 39 w in cases of uncomplicated gastroschisis. Bianchi's approach is an option in simple gastroschisis. Sutureless closure is suggested when general anesthesia can be avoided, sutured closure. If anesthesia is required. Silo treatment without ventilation and general anesthesia can be considered. In CG with atresia primary intestinal repair can be attempted if the condition of patient and intestine allows. Enteral feeds for simple gastroschisis should start within 14 days.

The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

OBJECTIVE: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection. DATA SOURCES: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www. CLINICALTRIALS: gov), and gray literature sources were searched from inception to March 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and quasi-randomized studies administering 8 g/d of oral valacyclovir in pregnant women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy were included. METHODS: All corresponding authors of the eligible studies were contacted. Cochrane's Risk of Bias 2 and Risk Of Bias In Non-randomised Studies - of Interventions tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. A 1-stage individual patient data meta-analysis was performed, using a generalized linear mixed model, clustered by the different trials. A subgroup analysis was performed, assessing separately the effect of valacyclovir in the periconceptional period and first trimester of pregnancy. RESULTS: Overall, 3 studies were included in the analysis (n=527 women). Valacyclovir reduced the vertical transmission rate of cytomegalovirus (adjusted odds ratio, 0.34; 95% confidence interval, 0.18-0.61). This reduction was apparent for both periconceptional period (adjusted odds ratio, 0.34; 95% confidence interval, 0.12-0.96) and first-trimester (adjusted odds ratio, 0.35; 95% confidence interval, 0.16-0.76) infections. Moreover, valacyclovir reduced the rate of neonatal infection (adjusted odds ratio, 0.30; 95% confidence interval, 0.19-0.47), in both periconceptional period (adjusted odds ratio, 0.30; 95% confidence interval, 0.14-0.61) and first-trimester (adjusted odds ratio, 0.30; 95% confidence interval, 0.17-0.54) infections. Furthermore, valacyclovir reduced the rate of termination of pregnancy because of cytomegalovirus-associated severe fetal findings (adjusted odds ratio, 0.23; 95% confidence interval, 0.22-0.24). The gestational age at the initiation of treatment has a positive correlation with all outcomes. The overall prevalence of severe side effects was 2.1%. CONCLUSION: A dosage of 8 g/d of oral valacyclovir reduced the vertical transmission rates of cytomegalovirus following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy, with a low incidence of side effects.

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.

Ultrasound-assessed lung aeration, oxygenation and respiratory care in neonatal bile acid pneumonia: A nested case-control study.

AIM: Neonatal bile acid pneumonia (NBAP) occurs in neonates following obstetric cholestasis. We aimed to study the lung aeration and respiratory support of NBAP. METHODS: Nested, case/control study enrolling age-matched neonates with NBAP, respiratory distress syndrome (RDS) or transient tachypnoea (TTN). Lung aeration and oxygenation were assessed with lung ultrasound score, oxygenation index and SpO2 /FiO2 . RESULTS: Nineteen, 22 and 25 neonates with NBAP, RDS and TTN, respectively were studied (mean gestational age = 33 (2.2) weeks, 30 (45.5%) males). Upon admission, RDS patients had the worst lung ultrasound score (p = 0.022) and oxygenation index (p = 0.001), while NBAP and TTN neonates had similar values. At the worst time-point, NBAP and RDS patients showed similar oxygenation index (NBAP: 4.6 [2], RDS: 5.7 [3]) and SpO2 /FiO2 (NBAP: 3.1 [1.1], RDS: 2.7 [1]) which were worse than those of TTN patients (oxygenation index: p = 0.015, SpO2 /FiO2 : p = 0.001). RDS neonates needed the longest continuous positive airway pressure and highest mean airway pressure, but NBAP neonates needed invasive ventilation (26.3%, p = 0.01) and surfactant (31.6%, p = 0.003) more often than TTN patients who never needed these. CONCLUSION: NBAP was a mild disorder in the first hours of life but subsequently worsened and became similar to RDS.

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

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

Trial of labour versus elective caesarean delivery for estimated large for gestational age foetuses after prior caesarean delivery: a multicenter retrospective study.

BACKGROUND: Lower rates of successful trial of labor after cesarean (TOLAC) in association with fetal macrosomia were previously reported. This study aimed to compare TOLAC to elective caesarean delivery (CD) in women with estimated fetal weight large for gestational age (eLGA) and a prior CD. Primary outcome was to analyse the mode of delivery in case of TOLAC. Secondary outcome was to compare maternal and foetal morbidity. METHODS: We conducted a retrospective, descriptive, multicentric, cohort study in five maternity units between January and December 2020. Inclusion criteria were: women with a single prior CD and eLGA or neonatal weight > 90th percentile with singleton pregnancy and gestational age ≥ 37 weeks. MAIN OUTCOME MEASURES: rate of vaginal delivery, maternal and fetal morbidity including: shoulder dystocia, neonatal hospitalization, fetal trauma, neonatal acidosis, uterine rupture, 3rd and 4th perineal tears, post-partum hemorrhage, and a need for blood transfusion. RESULTS: Four hundred forty women met inclusion criteria, including 235 (53.4%) eLGA. 170 (72.3%) had a TOLAC (study group) and 65 (27.7%) an elective CD (control). 117 (68.82%) TOLAC had a vaginal delivery. No significant differences were found between the two groups in the rates of: postpartum haemorrhage, transfusion, Apgar score, neonatal hospitalization, and foetal trauma. Cord lactate was higher in the case of TOLAC (3.2 vs 2.2, p < 0.001). Median fetal weight was 3815 g (3597-4085) vs. 3865 g (3659-4168): p = 0.068 in the study vs. controls group respectively. CONCLUSION: TOLAC for eLGA fetuses is legitimate because there is no difference in maternal-fetal morbidity, and the CD rate is acceptable.

Efficacy of early intrauterine balloon tamponade for immediate postpartum hemorrhage after vaginal delivery: a randomized clinical trial.

BACKGROUND: Many questions remain about the appropriate use of intrauterine balloon devices in postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. Available data suggest that early use of intrauterine balloon tamponade might be beneficial. OBJECTIVE: This study aimed to compare the effect of intrauterine balloon tamponade used in combination with second-line uterotonics vs intrauterine balloon tamponade used after the failure of second-line uterotonic treatment on the rate of severe postpartum hemorrhage in women with postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. STUDY DESIGN: This multicenter, randomized, controlled, parallel-group, nonblinded trial was conducted at 18 hospitals and enrolled 403 women who had just given birth vaginally at 35 to 42 weeks of gestation. The inclusion criteria were a postpartum hemorrhage refractory to first-line uterotonics (oxytocin) and requiring a second-line uterotonic treatment with sulprostone (E1 prostaglandin). In the study group, the sulprostone infusion was combined with intrauterine tamponade by an ebb balloon performed within 15 minutes of randomization. In the control group, the sulprostone infusion was started alone within 15 minutes of randomization, and if bleeding persisted 30 minutes after the start of sulprostone infusion, intrauterine tamponade using the ebb balloon was performed. In both groups, if the bleeding persisted 30 minutes after the insertion of the balloon, an emergency radiological or surgical invasive procedure was performed. The primary outcome was the proportion of women who either received ≥3 units of packed red blood cells or had a calculated peripartum blood loss of >1000 mL. The prespecified secondary outcomes were the proportions of women who had a calculated blood loss of ≥1500 mL, any transfusion, an invasive procedure and women who were transferred to the intensive care unit. The analysis of the primary outcome with the triangular test was performed sequentially throughout the trial period. RESULTS: At the eighth interim analysis, the independent data monitoring committee concluded that the incidence of the primary outcome did not differ between the 2 groups and stopped inclusions. After 11 women were excluded because they met an exclusion criterion or withdrew their consent, 199 and 193 women remained in the study and control groups, respectively, for the intention-to-treat analysis. The women's baseline characteristics were similar in both groups. Peripartum hematocrit level change, which was needed for the calculation of the primary outcome, was missing for 4 women in the study group and 2 women in the control group. The primary outcome occurred in 131 of 195 women (67.2%) in the study group and 142 of 191 women (74.3%) in the control group (risk ratio, 0.90; 95% confidence interval, 0.79-1.03). The groups did not differ substantially for rates of calculated peripartum blood loss pf ≥1500 mL, any transfusion, invasive procedure, and admission to an intensive care unit. Endometritis occurred in 5 women (2.7%) in the study group and none in the control group (P=.06). CONCLUSION: The early use of intrauterine balloon tamponade did not reduce the incidence of severe postpartum hemorrhage compared with its use after the failure of second-line uterotonic treatment and before recourse to invasive procedures.

Abnormalities of the corpus callosum. Can prenatal imaging predict the genetic status? Correlations between imaging phenotype and genotype.

OBJECTIVE: Recent studies have evaluated prenatal exome sequencing (pES) for abnormalities of the corpus callosum (CC). The objective of this study was to compare imaging phenotype and genotype findings. METHOD: This multicenter retrospective study included fetuses with abnormalities of the CC between 2018 and 2020 by ultrasound and/or MRI and for which pES was performed. Abnormalities of the CC were classified as complete (cACC) or partial (pACC) agenesis of the CC, short CC (sCC), callosal dysgenesis (CD), interhemispheric cyst (IHC), or pericallosal lipoma (PL), isolated or not. Only pathogenic (class 5) or likely pathogenic (class 4) (P/LP) variants were considered. RESULTS: 113 fetuses were included. pES identified P/LP variants for 3/29 isolated cACC, 3/19 isolated pACC, 0/10 isolated sCC, 5/10 isolated CD, 5/13 non-isolated cACC, 3/6 non-isolated pACC, 8/11 non-isolated CD and 0/12 isolated IHC and PL. Associated cerebellar abnormalities were significantly associated with P/LP variants (OR = 7.312, p = 0.027). No correlation was found between phenotype and genotype, except for fetuses with a tubulinopathy and an MTOR pathogenic variant. CONCLUSIONS: P/LP variants were more frequent in CD and in non-isolated abnormalities of the CC. No such variants were detected for fetuses with isolated sCC, IHC and PL.

Management and survival of foetuses with trisomy 18 in a French retrospective cohort.

OBJECTIVES: The main objective of this study was to evaluate parents' current demands following the announcement of trisomy 18 and maternal risks. MATERIAL AND METHODS: A single-centre retrospective study was performed in the Paris Saclay Foetal Medicine Department from 2018 to 2021. All patients followed up in the department who had cytogenetic confirmation of trisomy 18 were included. RESULTS: 89 patients were recruited. The most common malformations at ultrasound examination were cardiac or brain abnormalities, distal arthrogryposis as well as severe intrauterine growth retardation. 29% of foetuses with trisomy 18 had more than three malformations. 77.5% of patients requested medical termination of pregnancy. Among the 19 patients who chose to continue their pregnancy, 10 (52.6%) presented with obstetrical complications, of which 7 (41.2%) experienced stillbirth; five babies were born alive with no survival at 6 months. CONCLUSION: In France, in the case of foetal trisomy 18, most women request termination of pregnancy. In the post-natal period, the management of a newborn with trisomy 18 is oriented towards palliative care. The mother's risk of obstetrical complications should be part of counselling. Follow-up, support and safety should be the goal of management of these patients, regardless of the patient's choice.

Transmission of SARS-CoV-2 from mother to fetus or neonate: What to know and what to do?

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.

Nasopharyngeal SARS-CoV-2 load and perinatal outcomes after maternal infection diagnosed close to delivery.

BACKGROUND: The occurrence of COVID-19 during the pregnancy can cause several negative maternal and neonatal outcomes. Nasopharyngeal viral load is associated with inflammatory markers and might influence the disease severity in non-pregnant patients, but there are no data about the relationship between viral load and perinatal outcomes in pregnant patients. OBJECTIVE: To investigate the hypothesis that nasopharyngeal SARS-CoV-2 load (estimated with real-time polymerase chain reaction delta cycle (ΔCt), measured in hospital clinical laboratories) is associated with perinatal outcomes, when COVID-19 is diagnosed in the third trimester of pregnancy. STUDY DESIGN: International, retrospective, observational, multi-center, cohort study enrolling 390 women (393 neonates, three pairs of twins), analyzed with multivariate generalized linear models with skewed distributions (gamma) and identity link. The analyses were conducted for the whole population and then followed by a subgroup analysis according to the clinical severity of maternal COVID-19. RESULTS: The estimated viral load in maternal nasopharynx is not significantly associated with gestational age at birth (adjusted B: -0.008 (95%CI: -0.04; 0.02); p = 0.889), birth weight (adjusted B: 4.29 (95%CI: -25; 35); p = 0.889), weight Z-score (adjusted B: -0.01 (95%CI: -0.03; 1); p = 0.336), 5' Apgar scores (adjusted B: -0. -9.8e-4 (95%CI: -0.01; 0.01); p = 0.889), prematurity (adjusted OR: -0.97 (95%CI: 0.93; 1.03); p = 0.766) and the small for gestational age status (adjusted OR: 1.03 (95%CI: 0.99; 1.07); p = 0.351). Similar results were obtained in subgroup analyses according to COVID-19 clinical severity. CONCLUSIONS: The estimated maternal nasopharyngeal viral load in pregnant women affected by COVID-19 during the third trimester is not associated with main perinatal outcomes.

Systematic review and synthesis of stillbirths and late miscarriages following SARS-CoV-2 infections.

OBJECTIVE: 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. DATA SOURCES: PubMed and Web of Science databases were searched between December 1, 2019, and April 30, 2022. STUDY ELIGIBILITY CRITERIA: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.