Caudal regression in fetus with de novo SMARCA2 pathogenic variant.

Nicolaides-Baraitser syndrome (NCBRS) is a rare autosomal dominant genetic condition that is characterized by severe intellectual disability, dysmorphic facial features, short stature, sparse hair, and early onset seizures. This diagnosis is established by suggestive clinical findings and the identification of a heterozygous SMARCA2 pathogenic variant by molecular genetic testing. There are not, however, consensus clinical diagnostic criteria for this condition as there are so few documented cases. Here, we present a case of prenatally diagnosed caudal regression with sacral agenesis and congenital vertical talus (rocker bottom feet) that was ultimately found to have a de novo SMARCA2 pathogenic variant. The patient had an amniocentesis with normal karyotype and microarray followed by failed direct rapid whole exome sequencing (WES) due to maternal cell contamination. She elected for termination of the pregnancy based on the clinical prognosis of the ultrasound findings; WES revealed a pathogenic variant after her termination. We believe this is the first case of these findings associated with NCBRS. If any future cases of either finding are found in association with a SMARCA2 genetic variant, caudal regression and rocker bottom feet should be included in the spectrum of physical traits associated with this pathogenic variant.

Incidence of small-for-gestational-age infant birthweight following early intertwin fetal growth discordance in dichorionic and monochorionic twin pregnancies.

BACKGROUND: Serial growth scans are routinely recommended for twin pregnancies to identify fetal growth restriction (defined as an estimated fetal weight of <10th percentile), which can result in increased perinatal morbidity and mortality. However, the clinical significance of early intertwin growth discordance in the absence of fetal growth restriction remains unclear. OBJECTIVE: This study aimed to compare the rates of small-for-gestational-age infants among twin pregnancies with intertwin growth discordance in the absence of fetal growth restriction with that among twin pregnancies with concordant, normal growth identified by ultrasound between 24 0/7 and 31 6/7 weeks' gestation. STUDY DESIGN: This was a retrospective cohort study of twin deliveries at a single hospital from 2010 to 2019. Pregnancies without fetal growth restriction were categorized as discordant or concordant using the earliest prenatal growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation. Discordance was defined as an estimated fetal weight difference of ≥18% between twins. Pregnancies with major fetal anomalies, no growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation, or twin-twin transfusion syndrome were excluded. The cohort was stratified by chorionicity. Our primary outcome was small-for-gestational-age defined as <10th percentile per the Fenton growth curve at delivery. Secondary outcomes included gestational age at delivery, mode of delivery, neonatal intensive care unit admission, length of stay, and neonatal complications and placental pathology. RESULTS: Of the 707 twin pregnancies that met the inclusion criteria, 558 (79%) were dichorionic and 149 (21%) were monochorionic. Most pregnancies were concordant on ultrasound between 24 0/7 and 31 6/7 weeks' gestation (dichorionic, 93%; monochorionic, 87%). Regardless of chorionicity, twin pregnancies with discordance at ultrasound, were more likely to have a small-for-gestational-age infant than concordant twin pregnancies (dichorionic: 51% vs 29%; P=.002; monochorionic: 65% vs 24%; P<.001). Furthermore, women with twin pregnancies with discordance were delivered at an earlier gestational age (dichorionic: 36 weeks [interquartile range, 33-36] vs 34 weeks [interquartile range, 34-38]; P<.001; monochorionic: 34 weeks [interquartile range, 32-34] vs 36 weeks [interquartile range, 34-37]; P=.003). Pregnancies with growth discordance were more likely to be delivered by cesarean delivery (dichorionic: 90% vs 72%; P=.01; monochorionic: 65% vs 60%; P=.70), although this was only statistically significant for dichorionic twin pregnancies. Neonates of pregnancies with growth discordance had a higher incidence of respiratory distress syndrome (dichorionic: 54% vs 37%; P=.04; monochorionic: 70% vs 45%; P=.04) and neonatal intensive care unit admission (dichorionic: 71% vs 50%; P=.01; monochorionic: 90% vs 65%; P=.03). Furthermore, dichorionic infants had longer neonatal intensive care unit stays (30 [interquartile range, 18-61] vs 18 [interquartile range, 10-35] days; P=.02). CONCLUSION: Regardless of chorionicity, twin pregnancies with discordance without fetal growth restriction identified on growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation were nearly twice as likely to develop small-for-gestational-age neonates, deliver earlier in gestation, and experience greater neonatal morbidity than twin pregnancies without discordance. Patients with pregnancies complicated by isolated intertwin discordance between 24 0/7 and 31 6/7 weeks' gestation will need counseling regarding adverse perinatal outcomes.

Hypertensive Disorders of Pregnancy.

Preeclampsia is a hypertensive disorder of pregnancy that is a leading cause of maternal and perinatal morbidity and mortality. The condition presents heterogeneously at varying gestational ages. Primary prevention for preeclampsia with low-dose aspirin is recommended for patients with clinical risk factors. Despite extensive research, there is no clearly defined pathophysiology for preeclampsia or treatment for preeclampsia besides delivery of the placenta. Delivery of patients with preeclampsia without severe features is indicated in the early term period at 37 weeks' gestation and sooner if the patient develops severe preeclampsia. Management of preterm preeclampsia is guided by close assessment of the status of the pregnant woman and fetus, blood pressure control, and surveillance for any clinical progression to a more severe form of preeclampsia that may require preterm delivery. In a preterm gestation affected by preeclampsia, expectant management is intended to provide neonatal benefit though it does assume some maternal risk. Future research will hopefully further delineate the pathophysiology of the condition with the ultimate goal of finding a treatment to avoid associated morbidity and preterm delivery.