Russell S. Miller

Objective: Foetal‐neonatal alloimmune thrombocytopaenia (FNAIT) is a rare disease, most commonly caused by maternal alloantibodies to human platelet antigen (HPA)‐1a that can result in severe bleeding. The present study was designed to determine the frequency of higher risk for HPA‐1a alloimmunisation and development of FNAIT among a racially and ethnically diverse cohort of pregnant women. Design: Longitudinal, prospective, non‐interventional, natural history study. Setting: Conducted across 28 sites in North America and Europe. Population: Pregnant women (≥ 18 years) with no history of FNAIT. Methods: Blood samples were collected at 10–14 weeks' gestation and a sequential screening algorithm applied: maternal HPA‐1a/1b genotyping, human leukocyte antigen [HLA]‐DRB3*01:01 allele status, anti‐HPA‐1a antibody status and foetal HPA‐1 genotype. Main Outcome Measures: Number of women at higher risk for HPA‐1a alloimmunisation (i.e., those who are HPA‐1b/b, HLA‐DRB3*01:01 positive, anti‐HPA‐1a antibody negative and carrying an HPA‐1a‐positive foetus) that alloimmunise. Results: Of the 14 114 participants screened, 1.7% were HPA‐1b/1b genotype, which varied according to race and geography. Of 24 women at higher risk for FNAIT, five were lost to follow‐up with no post‐partum test for alloimmunisation. At Week 10 post‐partum, 2/19 higher risk participants (11%; 95% confidence interval [CI]: 1.3%, 33.1%) demonstrated anti‐HPA‐1a antibodies, while 17 remained negative. Pre‐existing anti‐HPA‐1a antibodies were identified in 18 other HPA‐1bb, DRB3*01:01 positive women at screening. Conclusions: This prospective study confirms the rarity of a population at higher risk for HPA‐1a alloimmunisation and FNAIT, describes the risk among Black and Asian women, and establishes a rigorous methodology to assess for risk of HPA‐1a immunisation.

Introduction: Cleft lip and palate (CLP) are common congenital disruptions of the orofacial cleft and are associated with numerous genetic conditions. This study examines prenatal findings, clinical outcomes, and genetic findings among prenatally diagnosed CLP, with a focus on the yield of next‐generation sequencing (NGS). Methods: This was a retrospective cohort study of prenatally diagnosed CLP presenting to a tertiary‐care referral center between 2017 and 2024. Inclusion required pre‐/postnatal diagnostic genetic testing. Imaging findings, genetic diagnoses, and delivery and postnatal outcomes were compared between those with isolated CLP (iCLP) and CLP with additional anomalies (CLP+). t ‐tests, Wilcoxon rank‐sum test, chi‐square test, or Fisher's exact test were used as appropriate. Results: A total of 57 pregnancies met inclusion criteria: 19 (33.3%) iCLP and 38 (66.7%) CLP+. Among CLP+, the most common additional prenatally detected anomalies were central nervous system (55.3%) and cardiac (52.6%). Groups had similar rates of termination and live birth (26.0% and 68.0% overall, respectively). Neonatal intensive care unit (NICU) admission was frequent at 70.6%, and similar between groups (50.0% iCLP vs. 81.8% CLP+, p = 0.11). Across the cohort, 21 (36.8%) pregnancies had reported findings from genetic testing, with 16 (28.1% of total cohort, 76.2% of those with genetic findings) possessing findings explanatory of CLP. CLP+ pregnancies were more likely to have explanatory genetic findings (36.8% vs. 10.5%, p = 0.04). Eleven of 16 (68.8%) likely causative findings were detected via karyotype/CMA. Among 29 patients with NGS, five (17.2%) had likely causative variants not detected by karyotype/CMA. NGS increased overall pathogenic diagnostic yield from 19.3% to 28.1% and diagnosed additional clinically relevant findings in three cases. Conclusion: Postnatal outcomes were overall similar between groups, with high rates of NICU admission. While CLP+ had higher rates of genetic findings, all CLP had risk of genetic disorders. In cases with non‐causative karyotype/CMA, sequencing revealed explanatory diagnostic variants in one in six cases, increasing diagnostic yield by nearly 10%. We advocate for comprehensive prenatal imaging and diagnostic genetic evaluation, including sequencing, for all prenatal CLP cases.

Introduction: Pulmonary hypoplasia and severe pulmonary hypertension associated with severe oligo/anhydramnios may be mitigated by amnioinfusion in fetal bilateral renal agenesis (BRA). We report fetal cardiovascular testing in live-born BRA subjects of the Renal Anhydramnios Fetal Therapy (RAFT) trial. Methods: Fetuses in the BRA RAFT trial cohort underwent third trimester echocardiography with maternal hyperoxia (MH). Echocardiographic parameters, compared between baseline and MH, are presented for expectant management and amnioinfusion participants using descriptive and inferential statistics. Results: Of 20 BRA pregnancies, 17 had amnioinfusions and 3 expectant management; 13 had fetal echocardiograms. Middle cerebral artery pulsatility index (PI) increased with MH (1.82 vs. 2.12, p = 0.032), as did umbilical artery PI (0.89 vs. 1.02, p = 0.056), without change in cardiac output or right ventricular percentage of the output, as expected. Fetuses in the intervention arm showed significant decrease in pulmonary artery PI compared to no decrease or an increase in the control arm. All fetuses with clear reactivity had favorable respiratory status at 30 days of life. Minimal reactivity (<10%) was not predictive of poor outcome. Pulmonary artery branch dimensions were significantly larger in the treated fetuses. Conclusion: Fetal echocardiography with MH provides antenatal evidence of rescued pulmonary phenotype in BRA fetuses undergoing serial percutaneous amnioinfusions.

Introduction We present a case of spontaneous premature ductus arteriosus (DA) closure following modified interstitial laser ablation (ILA) of a giant chorangioma (GC) in a fetus with evidence of hydrops. Case presentation A 26-week ultrasound revealed a 10-cm GC in the posteriorly located placenta with signs of fetal hydrops, polyhydramnios, and elevated middle cerebral artery peak systolic velocity (MCA PSV) of 1.9 MoM. Preoperative fetal echocardiogram showed elevated combined cardiac output (753 ml/kg/min) without structural abnormalities. Modified ILA targeting the branches of the feeder artery with an extended-pulse technique (30 seconds at 40 Watts) followed by intrauterine fetal transfusion were performed without complications. On post-operative day (POD) 1, new onset of ductus venosus flow reversal was noted, which was attributed to post-procedural hemodynamics. Fetal echocardiography on POD 5 suggested constriction of DA; follow-up confirmed complete DA closure and secondary right heart dysfunction. The pregnancy was managed expectantly with at least weekly echocardiograms. Digoxin and hyperoxygenation for fetal heart failure did not change DA caliber. Acetaminophen and fluoxetine were discontinued without improvement. After an uncomplicated term cesarean delivery (indication: breech), the female neonate was discharged home on day of life 3. Currently, the child is 6 months old and healthy. Conclusion Modified ILA for GC followed by expectant management of associated DA closure yielded a term delivery with a favorable outcome.

Introduction: Limited data exist regarding outcomes when pre- and periviable PPROM (PPROM ≤26 weeks of gestation) occurs as a complication of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). Methods: This is a retrospective cohort study of FLS cases performed at a single institution between January 2015 and May 2021. Study inclusion was limited to patients with monochorionic-diamniotic twin pregnancies complicated by TTTS who underwent FLS. Patients were grouped by pPPROM status, and further stratified to those continuing with expectant management, and outcomes were compared between groups. The primary outcome was survival to live birth of at least one twin. Results: During the study period, 171 patients underwent FLS and a total of 96 (56.1%) subjects satisfied inclusion criteria. Among included subjects, 18 (18.8%) experienced pPPROM after FLS and 78 (81.2%) did not. Baseline characteristics were similar between groups. Among patients with pPPROM, 11 (61.1%) pursued expectant management and 7 (38.9%) opted for pregnancy termination. Among expectantly managed subjects, median pPPROM-to-delivery interval was 47.0 days (6.0–66.0 IQR) with a median gestational age at delivery of 29+1 weeks (24 + 4–33 + 6 IQR). Rates of survival to live birth of at least one twin (90.9% vs. 96.2% p = 0.42) were similar between those with pPPROM undergoing expectant management and those without pPPROM. Dual survivorship (45.5% vs. 78.2%, p = 0.03), perinatal survival to live birth (68.2% vs. 87.2%, p = 0.05), and perinatal survival to newborn hospital discharge (59.1% vs. 85.9%, p = <0.01) were all significantly lower among those with pPPROM. Gestational age at delivery was lower among those continuing with pregnancies complicated by pPPROM (29 + 1 vs. 32+5 weeks, p = <0.01). Conclusion: Survival of at least one twin to live birth remained high among those pursing expectant management after experiencing post-FLS pPPROM, suggesting that the outlook after this complication is not necessarily poor. However, this complication was associated with lower chances of dual survival and greater prematurity.