Nonimmune hydrops fetalis: identifying the underlying genetic etiology.

PURPOSE: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. METHODS: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. RESULTS: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach-Merritt syndrome. CONCLUSION: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.

Outcomes of a Negative Rapid Influenza Diagnostic Test in Pregnant Women.

OBJECTIVE: The objective of this study was to evaluate the negative predictive value (NPV) of a rapid influenza diagnostic test (RIDT) compared with polymerase chain reaction (PCR) in pregnant women. STUDY DESIGN: Retrospective cohort study of pregnant women with a negative RIDT followed by confirmatory PCR for influenza A, H1N1, and B during the influenza seasons from 2012 to 2015. RESULTS: The NPV of the RIDT was 85.4% (211 of 247), 93.5% (231 of 247), and 97.9% (242 of 247) for influenza A, H1N1, and B, respectively. Antiviral treatment was administered to 47.2% (17 of 36) of women with a false-negative RIDT for influenza A compared with 9.0% (19 of 211) of women with a true-negative RIDT (p< 0.001). Patients were more likely to receive antiviral treatment if they were feverish (adjusted odds ratio [aOR]: 6.05, 95% confidence interval [CI]: 1.83-20.03), had cough (aOR: 6.43, 95% CI: 1.06-39.26), dyspnea (aOR: 6.41, 95% CI: 1.63-25.29), or had a subsequently positive PCR (aOR: 9.41, 95% CI: 3.13-28.31). CONCLUSION: Up to 14.5% of women with a negative RIDT in pregnancy had positive influenza A by PCR of whom more than half did not receive antiviral treatment.

The Effect of Intrapartum Vancomycin on Vaginal Group B Streptococcus Colony Counts.

OBJECTIVE: To define the temporal relationship between intrapartum intravenous vancomycin administration and vaginal group B streptococcus (GBS) colony counts. STUDY DESIGN: Prospective cohort study conducted from October 2014 to February 2017. Women with antenatal cultures demonstrating GBS colonization and a plan for vancomycin administration were eligible. Intrapartum vaginal cultures were collected prior to the first vancomycin infusion and every 2 hours up to five collections or delivery. Results were analyzed in two groups: participants with at least one positive intrapartum culture and those without any positive intrapartum cultures. RESULTS: A total of 63 women were enrolled. Among consented women, a total of 8 were excluded and 3 participants' cultures were never plated, thus leaving a total of 52 women for analysis. The degree of vaginal GBS colonization varied between subjects and was not normally distributed. Colony counts dropped rapidly from hour 0 to hour 2 (median: 6.0 × 108 vs. 1.0 × 108, p < 0.01). Standardizing hour 0 colony counts to 100%, the percent decline in colony counts from hour 0 to hour 2 was significant (p = 0.03), and at each subsequent time point fell further. CONCLUSION: GBS vaginal colony counts fall rapidly after intrapartum vancomycin administration.

Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis.

Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the PIEZO1 gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally. We present a case of a woman with recurrent pregnancies affected by NIHF because of novel compound heterozygous variants in the PIEZO1 gene diagnosed prenatally using exome sequencing (ES). Two variants in PIEZO1 (c.3206G>A and c.6208A>C) were identified that were inherited from the father and mother, and are predicted to cause a nonsense and missense change, respectively, in the PIEZO1 subunits. Ultrasound demonstrated severe bilateral pleural effusions, whole body edema and polyhydramnios. Histopathology revealed an increased number of lymphatic channels, many of which showed failure of luminal canalization. Sanger sequencing confirmed the same variants in a prior fetal demise. We provide phenotypic correlation with ultrasound and autopsy finding, review PIEZO1 variants as a cause of GLD and discuss the uses of prenatal ES to date.

Uptake of a Guideline for the Administration of a Rescue Course of Antenatal Corticosteroids.

OBJECTIVE: To evaluate use (both appropriate and inappropriate) of rescue corticosteroids before and after the implementation of a guideline for their use. METHODS: We conducted a retrospective cohort study using a pharmacy log to identify women who received an initial course of antenatal corticosteroids in the year before (2008) and in the 4 years (2009-2012) after implementation of the guideline. The charts were then reviewed to determine eligibility and assess receipt of rescue corticosteroids according to the guideline. Our primary study outcome was a temporal change in the percentage of appropriate rescue corticosteroid administration. RESULTS: Of 2,528 women who received a first course of corticosteroids, 142 (5.6%) were eligible for a rescue course, of whom 103 (73%) received it. The rate of appropriate administration increased from 18.2% (95% confidence interval [CI] 5-40%) in 2008 to 65.4% (95% CI 44-83%) in 2009, 93.5% (95% CI 79-99%) in 2010, 96.1% (95% CI 80-99%) in 2011, and 75.7% (95% CI 59-88%) in 2012 (P for test of trend <.001). Only 25 of these 103 eligible women (24.3%) delivered within 2-7 days of receipt of the rescue course. The rate of inappropriate administration among women who were not eligible for a rescue course (n=2,381) also rose from 0.4% (95% CI 0.04-1.4%) in 2008 to 1.9% (95% CI 0.9-3.5%) in 2009, 1.8% (95% CI 0.8-3.6%) in 2010, 2.4% (95% CI 1.2-4.3%) in 2011, and 2.2% (95% CI 1.1-4.0%) in 2012 (P for test of trend=.03). Among all recipients of rescue corticosteroids, 28% (41/144) were ineligible according to the guideline. CONCLUSION: Implementation of an institutional guideline for rescue corticosteroids was associated with a high rate of use among eligible women.