Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally and 11 were diagnosed postnatally: all 11 spontaneous survivors' genotypes had preserved embryonic zeta globin. We compared three groups of patients; Group 1 were prenatally diagnosed and alive at hospital discharge (n=14), Group 2 were prenatally diagnosed and deceased perinatally (n=5), Group 3 were postnatally diagnosed and alive at hospital discharge (n=11). Group 1 had better outcomes than Groups 2 and 3 in resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation correlated with higher neurodevelopmental (Vineland-3) scores (r= -0.72, P=0.02). Preterm delivery after IUT was seen in 3/16 (19%) of patients who continued their pregnancy. When we combined our data with those from two published series, patients who received ≥2 IUTs had better outcomes than those with 0-1 IUT, including resolution of hydrops, delivery ≥34 weeks' gestation, and 5-minute Apgar scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT versus 5/13 of the 0-1 IUT group (OR 2.74; P=0.01). Thus, fetal transfusions enable survival of patients with ATM with normal neurodevelopment even in patients presenting with hydrops. Non-directive prenatal counseling of expectant parents should include the option of IUTs.

Increased nuchal translucency Cleft lip and palate Microcephaly Lissencephaly Coloboma Cryptorchidism Craniosynostosis ACTB gene Baraitser-Winter syndrome

proper management protocol for these women is still a matter of debate. One management tool is the placental scan. We aimed to evaluate the utility of this tool in women with abnormal FTS analytes. STUDY DESIGN: Retrospective cohort study of all women who had FTS and delivered at a single referral center (2016-2018). FTS included PAPP-A, PlGF, free b-hCG and AFP. Placental sonographic assessment included morphologic description of the placenta, fetal growth estimation and measurement of the average uterine artery pulsatility index (UtA-PI). All women with abnormal FTS analytes had a placental scan. All women who had abnormal morphology of the placenta during the scan and/or mean UtA-PI >95% percentile for gestational age were excluded. We compared pregnancies of women with abnormal first trimester analytes and normal placental scan (study group) with those who had normal first trimester analytes (control). RESULTS: Overall, 6,514 women were included in the study, of which 343 (5.3%) comprised the study group. Women in the study group were characterized by a younger mean maternal age, and higher rates of IVF treatment and gestational hypertension (Table). Women in study group were almost twice as likely to have a preterm birth (PTB)< 37 weeks, and their neonates' mean birthweight was lower (Table). Nonetheless, the rate of FGR was similar between the groups (Figure). On multivariable logistic regression, women in the study group were more likely to have gestational hypertension [aOR 1.9 (95% CI 1.1-3.3)], and PTB< 37 weeks (aOR 2.1, 95% CI 1.4-.3.1), mainly due to abnormal PAPP-A [aOR 2.71 (1.44-5.11)]. Yet, their neonates were not at higher risk for FGR< 3rd, 5th, or 10th percentile [aOR 0.45 (95% CI 0.2-1.2), aOR 1.1 (95% CI 0.7-1.8) and aOR 1.1 (95% CI 0.8-1.5), respectively]. CONCLUSION: Following a normal placental scan, women at risk for FGR based on the FTS analytes do not have higher risk for FGR than their counterparts with normal FTS analytes.