Utility of chromosomal microarray analysis for the exploration of isolated and severe fetal growth restriction diagnosed before 24 weeks' gestation.

OBJECTIVE: This study aimed to evaluate the utility of chromosomal microarray analysis (CMA), for the genetic exploration of isolated and severe intrauterine growth restriction (IUGR) diagnosed before 24 weeks gestation (WG). METHODS: This retrospective study included singleton fetuses diagnosed with severe IUGR without structural anomalies before 24 WG referred between 2013 and 2021 who underwent prenatal genetic analysis. IUGR was defined by estimated fetal weight ≤3rd centile for gestational age. Genetic analysis, including QF-PCR and CMA, was systematically offered as part of the etiologic evaluation. RESULTS: Of 101 referred fetuses, CMA and QF-PCR were performed in 67 fetuses. Among these 67 cases, a total of 10.5% (7/67) chromosomal abnormalities were detected. CMA detected three pathogenic copy number variants (CNV) (3/67, 4.5%) and three variants of unknown signification (VUS) (3/67, 4.5%). Karyotype detected one chromosomal abnormality. All of the QF-PCR were normal. Two fetuses with pathogenic CNV shows Doppler abnormalities. CONCLUSION: Our study found that in fetuses with severe, isolated, and very early-onset growth restriction, the rate of pathogenic CNV detected by CMA was 4.5%. Although this cohort is too small to draw a definitive conclusion, the presence of Doppler abnormalities couldn't exclude the possibility of genetic abnormalities.

Impact of uterine balloon tamponade on the use of invasive procedures in severe postpartum hemorrhage.

INTRODUCTION: The aim of this study was to assess the impact of tamponade when uterotonic agents fail, on the need for surgery or interventional radiology. MATERIAL AND METHODS: All women who received sulprostone for postpartum hemorrhage were retrospectively compared over two periods [December 2008 to December 2010 without use of tamponade (period 1) and June 2011 to June 2013 with use of tamponade (period 2)] in the case of sulprostone failure (STROBE compliant retrospective cohort study). During period 2, interventional radiology or surgery was used only in the case of tamponade failure. RESULTS: 165 women were included (74 for period 1, 91 for period 2). The rate of interventional radiology or surgery significantly decreased from period 1 (21 of 74 women, 28.4%) to period 2 (six of 91 women, 6.6%, p = 0.0003). The rate of assumed failure of uterotonic agents was higher for period 2: 22 of 74 women (29.7%) during period 1, and 41 of 91 (45.1%, p = 0.0439) during period 2. The success rate of tamponade was 92.1% (35 of 38 women). CONCLUSIONS: Although the efficacy of tamponade should be viewed in the light of its widespread use, our findings confirm that tamponade significantly reduces the need for interventional radiology or surgery for postpartum hemorrhage treatment.

Is cell-free fetal DNA testing a safe option for women in a high-risk population after combined first-trimester testing?

OBJECTIVES: Our study aimed to examine the relevance of cell-free fetal DNA (cfDNA) testing on the screening of chromosomal defects and the issue of pregnancies in patients with a risk over 1:50 after the first-trimester combined test. METHODS: This is a retrospective monocentric study. We included all consecutive patients with a singleton pregnancy between January 2015 and December 2020 attending our fetal medicine center because the estimated risk for trisomy 21 after the first-trimester combined screening was over 1:50. The patients could either choose to have invasive testing or cell-free DNA testing. We collected data about the patient, the tests results (cfDNA, karyotype) and the pregnancy outcome (born alive, medical termination, miscarriage or intrauterine fetal death). RESULTS: We included 98 patients with an estimated risk for trisomy 21 over 1:50. We found a total of 14 major chromosomal abnormalities (14/98; 14.3%), of which: thirteen trisomies 21 and one triploidy 69, XXY. A cfDNA testing was chosen by 34 (34/98; 34.7%) patients. Among the pathological results of invasive testing, 5 (5/64; 7.8%) couldn't be targeted by cfDNA testing. Two of them were placental mosaicism, one a triploidy 69, XXY, and two defects inherited from a parent and considered benign. There was no miscarriage linked to an invasive test in the population study. CONCLUSION: In our monocentric cohort, a third of the patients choose cfDNA in a case of a risk over 1:50 after combined testing. Even if this cohort is too small to draw definitive conclusions, cfDNA could be safe in a high-risk population after combined testing. None of the chromosomal abnormalities found at the karyotype and non-detectable by cfDNA was a loss of information that impacted pregnancy follow-up. Further study could explore the input of Genome-Wide cfDNA and chromosomal micro-array in this population.

Genetic studies in isolated bilateral clubfoot detected by prenatal ultrasound.

OBJECTIVE: To evaluate the contribution of genetic investigations in case of isolated bilateral clubfoot detected by routine prenatal ultrasound. Pathogenic Copy Number Variations is about 3.9% in fetuses with isolated clubfoot (uni- or bilateral). We hypothesize that this rate could be higher in a homogenous group of fetuses with bilateral clubfoot. METHODS: This retrospective single-center study included all women referred to our fetal-medicine center between 2013 and 2020 after ultrasound detection of isolated bilateral clubfoot. Genetic counseling was offered in which the woman was offered an amniocentesis for CMA and targeted investigation for Prader-Willi Syndrome (PWS), Steinert's disease and Spinal Muscular Atrophy (SMA). RESULTS: 34 women were referred, 18 of them consented to undergo genetic studies by amniocentesis (18/34; 52.9%). Pathogenic copy number variations (CNVs) were found in 2/18 (11.1%) of cases. One of these CNVs was directly linked to the clubfoot pathology (a deletion in 5q31.1 containing PITX1 gene). Four fetuses (4/18, 22.2%) had variants of unknown significance (VUS). No PWS, SMA or Steinert's disease was found. No case diagnosed with isolated clubfoot prenatally had additional anomalies postnatally. CONCLUSIONS: In the case of bilateral isolated clubfoot detected at the antenatal ultrasound, invasive prenatal testing should be offered, and if accepted, a CMA should be done, as pathogenic variations were observed in up to 11.1% of women who got amniocentesis. The findings of this study do not support the systematic recommendation of molecular studies for PWS, SMA, Steinert's disease.

Predictors of successful manual rotation for occiput posterior positions.

OBJECTIVE: To identify predictors of the success of manual rotation of fetuses in an occiput posterior position. METHODS: A prospective, observational, single-center study included all women with a singleton pregnancy at term with a fetus in an occiput posterior position for whom manual rotation was attempted from December 1, 2013, to April 30, 2015 at a tertiary care maternity unit in Nancy, France. Occiput posterior position was confirmed by ultrasonography, and success of manual rotation was defined by the occiput anterior position of the fetus after the attempt. RESULTS: Occiput posterior position was diagnosed in 233 (9.2%) of the 2522 deliveries during the study period and the majority of cases were managed successfully by manual rotation (167 [71.7%]). Factors associated with successful rotation were fetal engagement (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.05-4.56), spontaneous labor (aOR 1.85, 95% CI 1.01-3.43), and no failure to progress (aOR 2.01, 95% CI 1.02-3.94). Successful manual rotation was associated with lower rates of cesarean (P<0.001) and instrumental (P<0.001) deliveries. CONCLUSION: Study findings suggested that manual rotation, especially after fetal engagement, succeeded more often when performed systematically than when it was attempted after failure to progress.

Variable phenotypic expression of Apert syndrome in monozygotic twins.

Apert syndrome in monozygotic twins can lead to different phenotypic expression of the disease in the two fetuses. Apert syndrome can be associated with congenital left diaphragmatic hernia and cleft palate.

Utero-placental vascularisation in normal and preeclamptic and intra-uterine growth restriction pregnancies: third trimester quantification using 3D power Doppler with comparison to placental vascular morphology (EVUPA): a prospective controlled study.

INTRODUCTION: Preeclampsia (PE) and intra-uterine growth restriction (IUGR) are two major pregnancy complications related to chronic utero-placental hypoperfusion. Three-dimensional power Doppler (3DPD) angiography has been used for the evaluation of utero-placental vascularisation and three vascular indices have been calculated: the vascularisation index (VI), flow index (FI) and vascularisation-FI (VFI). However, several technical endpoints hinder the clinical use of 3DPD as physical characteristics and machine settings may affect 3DPD indices, and so its clinical significance is not yet clear. OBJECTIVES: The primary objective is to better understand the clinical significance of 3DPD indices by evaluating the relationship between these indices and placental morphometry. Secondary objectives are (i) to determine the impact of machine settings and physical characteristics on 3DPD indices, and (ii) to evaluate physio-pathological placental vascularisation patterns. METHODS AND ANALYSIS: This is a prospective controlled study. We expect to include 112 women: 84 with normal pregnancies and 28 with PE and/or IUGR (based on our former cohort study on 3DPD indices for PE and/or IUGR prediction (unpublished data)). Within 72 h before planned or semi-urgent caesarean section, utero-placental 3DPD images with five different machine settings will be acquired. Placentas will be collected and examined after surgery and stereological indices (volume density, surface density, length density) calculated. The 3DPD indices (VI, FI and VFI) of the placenta and adjacent myometrium will be calculated. Correlation between Doppler and morphological indices will be evaluated by Pearson or Spearman tests. Agreement between 3DPD indices and morphological indices will be assessed by Bland and Altman plots. The impact of Doppler settings and maternal characteristics on 3DPD indices will be evaluated with a multivariate linear regression model. ETHICS: The study and related consent forms have been approved by the French Ethics Committee (CPP, Comité de Protection des Personnes) Est III on 4 March 2014.

Tracheal agenesis: a challenging prenatal diagnosis-contribution of fetal MRI.

Tracheal agenesis is a rare congenital anomaly. The prevalence is less than 1 : 50 000 with a male to female ratio of 2 : 1. This anomaly may be isolated but, in 93% of cases, it is part of polymalformative syndrome. The most evocative diagnosis situation is the ultrasonographic congenital high airway obstruction syndrome. Dilated airways, enlarged lungs with flattened diaphragm, fetal ascites and severe nonimmune hydrops can be observed. In the absence of a congenital high airway obstruction syndrome, the antenatal diagnosis of tracheal agenesis is difficult. Tracheal agenesis should be suspected in the presence of an unexplained polyhydramnios associated with congenital malformations. The fetal airway exploration should then be systematically performed by fetal thoracic magnetic resonance imaging. A case of Floyd's type II tracheal agenesis, detected during the postnatal period, is reported here. The retrospective reexamination of fetal magnetic resonance images showed that the antenatal diagnosis would have been easy if a systematical examination of upper airways had been performed. Prenatal diagnosis of tracheal agenesis is possible with fetal MRI but the really challenge is to think about this pathology.