Plea for systematic prenatal genes panel testing when facing isolated craniosynostosis on fetal imaging.

BACKGROUND: Prenatal diagnosis of craniosynostosis remains rare and challenging, easier in syndromes with craniosynostosis due to the association with other sonographic anomalies. Crouzon syndrome is the most frequent syndrome with craniosynostosis but is difficult to detect antenatally because of mild skull deformation without specific associated anomaly during gestation. CASE: This report presents the case of a fetus with Crouzon syndrome related to the variant c.1646A>C in exon 14 of the FGFR2 gene and presenting with apparently isolated scaphocephaly on fetal US. CONCLUSION: This observation supports the interest of systematic prenatal panel genes testing when facing an apparently isolated craniosynostosis diagnosed on fetal imaging, even if non-syndromic craniosynostosis are much more frequent in such situation. TEACHING POINTS: Syndromic craniosynostosis can appear as apparently isolated form on fetal imaging. Systematic prenatal panel genes testing can be contributive even when facing an apparently isolated craniosynostosis on fetal imaging.

Predictive factors for severe placental damage in pregnant women with SARS-CoV-2 infection.

INTRODUCTION: SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions. METHODS: We retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings. RESULTS: Twelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant. DISCUSSION: In these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes.

Combined first trimester screening for trisomy 21: Assessment of excess risk in case of free ß-human chorionic gonadotrophin between 5 and 10 multiples of the median.

OBJECTIVE: The first trimester combined risk of trisomy 21 is obtained by multiplying the risk related to maternal age by the likelihood ratios of nuchal translucency, free beta-human chorionic gonadotrophin (ß-hCG) and placenta associated plasma protein-A. Beyond five multiples of the median (MoM) of ß-hCG, the risk of trisomy 21 is truncated. The objective of the present study was to evaluate the evolution of the first trimester combined risk of trisomy 21 in individuals with first-trimester free-ß-hCG levels between 5 and 10 MoM. METHODS: We conducted a non-interventional cohort study from a 6-year database of combined first-trimester trisomy 21 screening of all individuals who underwent the screening in a French specialized medical analysis center. We included all pregnant individuals who had a serum-free ß-hCG between 5 and 10 MoM. Patients for whom the status of the fetus, with or without trisomy 21, was not identified by the outcome of the pregnancy or by a karyotype result were excluded from the study. The discriminatory capacity of free-ß-hCG above 5 MoM was studied by a receiver operating characteristic curve. We used an orthogonal polynomial regression to represent the evolution of likelihood ratios according to free-ß-hCG in MoM. RESULTS: Among 413 216 combined first-trimester screens of trisomy 21, 2239 (0.5%) screens met the inclusion criteria. In the selected population, 801 (35.8%) were excluded from the study because of missing fetal or neonatal status, and 46 (3.2%) fetuses out of 1438 included were diagnosed with trisomy 21. For free ß-hCG values between 5 and 10 MoM, the area under the curve is 0.56 (0.46-0.65). The scatterplot of the likelihood ratio of ß-hCG showed an increasing parabolic pattern: the likelihood of trisomy 21 increases with the free-ß-hCG threshold. CONCLUSION: To override the truncated risk of trisomy 21 in case of free ß-hCG values between 5 and 10 MoM, the study has allowed us to estimate the adjusted risk of trisomy 21, enabling health professionals to offer appropriate prenatal counseling.

Prevention of Neural Tube Defects by Folic Acid Supplementation: A National Population-Based Study.

Folic acid supplementation is recommended for neural tube defect prevention during pregnancy. We conducted an observational, retrospective national registry study to determine the rate of dispensing of periconceptional folic acid after prescription in a sample of French women representative of the general population. Our study population (n = 186,061) was a representative sample of the French population, recorded in the Health Data System database on pharmacy dispensing of medication and mandatory reporting of pregnancy. Between 2006 and 2016, 14.3% of pregnant women had a prescription for folic acid supplementation during the month preceding conception and for the first 12 weeks of pregnancy. Of these prescriptions, 30.9% were issued before the start of pregnancy. This percentage was lower for first pregnancies. The rate of pharmacy dispensing during the preconception period increased progressively from 3.8% to 8.3% between 2006 and 2016. In France, the rate of pharmacy dispensing of periconceptional folic acid after medical prescription is very low and does not follow international recommendations. It seems essential to implement awareness-raising policies targeting the general population and physicians regarding effective periconceptional supplementation, particularly starting in the preconception period. Clarification of international recommendations and fortification of flour could improve the efficacy of folate supplementation at population level.