The association of HBB-related significant hemoglobinopathies and low fetal fraction on noninvasive prenatal screening for fetal aneuploidy.

OBJECTIVES: HBB-related significant hemoglobinopathies have been anecdotally associated with low fetal fraction on noninvasive prenatal screening (NIPS). We sought to compare the difference in fetal fraction using NIPS in women with HBB-related significant hemoglobinopathies (HSH) and women with normal hemoglobin. STUDY DESIGN: This is a retrospective case-control study. Cases were women with a diagnosis of HSH using NIPS from a commercial laboratory. The comparison group was women with hemoglobin AA from a tertiary care center database. We tested for differences in median fetal fraction using quantile regression analysis, adjusting for maternal body weight and gestational age. RESULTS: This study includes 35 women with clinically significant HSH and a comparison group of 636 women with hemoglobin AA. Adjusting for gestational age and body weight, the median fetal fraction was 4.1 point lower in the HSH than in the comparison group (ß - 4.1; 95% -5.7 to -2.5, p < .05). The rate of no-calls due to low fetal fraction was significantly higher in the clinically significant HSH group than in the comparison group [HSH: n = 9/35, 25.7% versus comparison: n = 32/636, 5.0% (p < .001)]. CONCLUSION: Women with HSH were more likely to have a lower fetal fraction and ultimately a five-fold higher no-call rate. What's already known about this topic?Low fetal fraction is one of the most common causes of no-call result in noninvasive prenatal screeningHigh maternal weight, early gestational age and fetal aneuploidies are associated with low fetal fraction What does this study add?HBB-related significant hemoglobinopathies are associated with low fetal fractionReduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate.

Effect of Antibiotic Treatment of Amniotic Fluid Sludge.

BACKGROUND: Amniotic fluid sludge refers to the sonographic presence of echogenic, free-floating aggregates of debris located within the amniotic cavity near the internal cervical os of women with intact membranes. Clinically, it is independently associated with increased obstetric, infectious, and neonatal morbidity, including: short cervix, chorioamnionitis, and an increased risk of preterm birth. It is thought to be infectious in nature and has been described as an intrauterine bacterial biofilm. There is little evidence on the impact of treatment with antibiotics on outcome. OBJECTIVE: To determine whether outpatient antibiotics administered to women with amniotic fluid sludge would reduce preterm birth risk compared to no antibiotic treatment. MATERIALS AND METHODS: This was a retrospective cohort study of all patients diagnosed with amniotic fluid sludge by transvaginal sonography between 15 and 25 weeks' gestation in the outpatient ultrasound unit at a single academic center between 2010 and 2017. Patients were segregated according to whether they were treated with oral antibiotics at the time of diagnosis. Women with multiple gestation, fetal anomalies, preterm rupture of membranes prior to initial diagnosis of amniotic fluid sludge, and active preterm labor placenta previa and/or suspected accreta were excluded from analysis. Primary outcome of preterm birth at less than 37 weeks' gestation was compared by univariate and regression analysis to control for potential co-linear and/or confounding variables. Additional outcomes were compared by univariate analysis. RESULTS: A total of 181 patients were initially identified, and 97 patients met inclusion criteria. Of these patients, 51 were treated with oral antibiotics (46 azithromycin and 5 moxifloxacin), and 46 were not treated. The overall incidence of preterm birth at <37 weeks was 49.4 % (48 of 97) and preterm birth <28 weeks was 22.7% (22 of 97). There was no significant difference in preterm birth, either at <37 weeks (P = .47) or <28 weeks (P = .83) between the treated and untreated women. After adjusting for race, body mass index, tobacco use, cervical length, and preterm birth history, antibiotic treatment did not reduce the risk of preterm birth (adjusted odds ratio, 1.3; confidence interval, 0.77-1.9). No differences were seen in the incidence of preterm premature rupture of membranes (P = .94) or median latency from diagnosis to delivery (P = .47). Birthweight (P = .99), sepsis (P = .53), intraventricular hemorrhage (P = .95), and neonatal intensive care unit (NICU) admission (P = .08) were not affected by antibiotic treatment. Antibiotic treatment did not affect the incidence of either clinical or histologic chorioamnionitis (P = .92 and .14, respectively) or histologic stage 2-3 maternal or fetal inflammation (P = .94 and 0.58, respectively). Sonographic resolution of amniotic fluid sludge on first subsequent scan was seen in 34% of antibiotic-treated women and 43% of untreated women (P = .42). There was no difference in latency from diagnosis to delivery or mean gestational age at delivery according to whether sludge resolved or persisted at the first subsequent scan (P = .14 for each). CONCLUSION: Antibiotic treatment of amniotic fluid sludge is not associated with a reduction in premature birth. Likewise, antibiotic treatment of amniotic fluid sludge was not associated with improvement in other obstetric, neonatal, or pathologic variables. These findings suggest that the presumed infectious nature of sludge and subsequent adverse outcomes are not treated or improved by administration of azithromycin following midtrimester sonographic diagnosis.

First Report of Prenatal Ascertainment of a Fetus With Homozygous Loss of the SOX10 Gene and Phenotypic Correlation by Autopsy Examination.

The SOX10 gene plays a vital role in neural crest cell development and migration. Abnormalities in SOX10 are associated with Waardenburg syndrome Types II and IV, and these patients have recognizable clinical features. This case report highlights the first ever reported homozygous loss of function of the SOX10 gene in a human. This deletion is correlated using family history, prenatal ultrasound, microarray analysis of amniotic fluid, and ultimately, a medical autopsy examination to further elucidate phenotypic effects of this genetic variation. Incorporating the use of molecular pathology into the autopsy examination of fetuses with suspected congenital anomalies is vital for appropriate family counseling, and with the ability to use formalin-fixed and paraffin-embedded tissues, has become a practical approach in autopsy pathology.

Successful Continuation of Pregnancy After Treatment of Group A Streptococci Sepsis.

BACKGROUND: Invasive group A streptococci infections in pregnancy have historically led to severe maternal and neonatal morbidity and mortality. We are reporting a rare and novel case of successful treatment of third-trimester group A streptococci infection with early, aggressive intervention and maintenance of the pregnancy to term. CASE: A 35 year old woman initially presented with fever, flu-like symptoms, and preterm contractions at 34 weeks of gestation. She demonstrated signs of early stages of septic shock, ultimately attributed to group A streptococci bacteremia. Early, aggressive intervention allowed the pregnancy to continue until 38 weeks of gestation with normal maternal and neonatal outcomes. CONCLUSION: Early and aggressive treatment of invasive group A streptococci infection during pregnancy can potentially avoid severe maternal and perinatal morbidity and mortality with a successful continuation of pregnancy.