Victoria Berger

Preimplantation Diagnosis for Single Gene Disorders

Preimplantation genetic diagnosis (PGD) allows patients who are carriers or who are affected by genetic diseases to select unaffected embryos for transfer before becoming pregnant. The practice of PGD is evolving with rapid advances in technology and biopsy methods. Testing for a specific gene mutation can be performed in combination with 24-chromosome aneuploidy screening. Several unique applications of PGD are reviewed, including exclusion diagnosis for couples from Huntington disease families, testing for fragile X premutations, and human leukocyte antigen matching for stem cell donor siblings. Although PGD for single gene mutations allows patients to gain information about their embryos and perhaps avoid a difficult decision about whether or not to terminate an ongoing pregnancy, this technique also provides for much ethical debate encompassing the well-being of the prospective couple, embryo, child, and people in the community affected by the diseases being screened.

Perinatal Neuroprotection for Extremely Preterm Infants.

The preterm brain is vulnerable to injury through multiple mechanisms, from direct cerebral injury through ischemia and hemorrhage, indirect injury through inflammatory processes, and aberrations in growth and development. While prevention of preterm birth is the best neuroprotective strategy, this is not always possible. This article will review various obstetric and neonatal practices that have been shown to confer a neuroprotective effect on the developing brain.

Antenatal Corticosteroids for Preterm Premature Rupture of Membranes: Single or Repeat Course?

OBJECTIVE The aim of this article is to determine the risk of maternal chorioamnionitis and neonatal morbidity in women with preterm premature rupture of membranes (PPROM) exposed to one corticosteroid course versus a single repeat corticosteroid steroid course. STUDY DESIGN Secondary analysis of a cohort of women with singleton pregnancies and PPROM. The primary outcome was a clinical diagnosis of maternal chorioamnionitis. Using multivariate logistic regression, we controlled for maternal age, race, body mass index, diabetes, gestational age at membrane rupture, preterm labor, and antibiotic administration. Neonatal morbidities were compared between groups controlling for gestational age at delivery. RESULTS Of 1,652 women with PPROM, 1,507 women received one corticosteroid course and 145 women received a repeat corticosteroid course. The incidence of chorioamnionitis was similar between groups (single course = 12.3% vs. repeat course = 11.0%; p = 0.8). Women receiving a repeat corticosteroid course were not at increased risk of chorioamnionitis (adjusted odds ratio, 1.28; 95% confidence interval, 0.69-2.14). A repeat course of steroids was not associated with an increased risk of any neonatal morbidity. CONCLUSION Compared with a single steroid course, our findings suggest that the risk of maternal chorioamnionitis or neonatal morbidity may not be increased for women with PPROM receiving a repeat corticosteroid course.

Outcome and Treatment of Antenatally Diagnosed Nonimmune Hydrops Fetalis

Introduction: The objectives of this study were to evaluate the outcome of nonimmune hydrops fetalis in an attempt to identify independent predictors of perinatal mortality. Material and Methods: A retrospective cohort study was conducted including all cases of nonimmune hydrops from two tertiary care centers. Perinatal outcome was evaluated after classifying nonimmune hydrops into ten etiological groups. We examined the effect of etiology, site of fluid accumulation, and gestational age at delivery on postnatal survival. Neonatal mortality and hospital discharge survival were compared between the expectant management and fetal intervention groups among those with idiopathic etiology. Results: A total of 142 subjects were available for analysis. Generally, nonimmune hydrops carried 37% risk of neonatal mortality and 50% chance of survival to discharge, which varies markedly based on the underlying etiology. Ascites was an independent predictor of perinatal mortality (p value = 0.003). There was nonsignificant difference in neonatal mortality and hospital discharge survival among idiopathic cases that were managed expectantly versus those in whom fetal intervention was carried out. Discussion: The outcome of nonimmune hydrops varies largely according to the underlying etiology and the presence of ascites is an independent risk factor for perinatal mortality. In our series, fetal intervention did not offer survival advantage among fetuses with idiopathic nonimmune hydrops.

Using exome sequencing to decipher family history in a healthy individual: Comparison of pathogenic and population MTM1 variants

When a family encounters the loss of a child early in life, extensive genetic testing of the affected neonate is sometimes not performed or not possible. However, the increasing availability of genomic sequencing may allow for direct application to families in cases where there is a condition inherited from parental gene(s). When neonatal testing is not possible, it is feasible to perform family testing as long as there is optimal interpretation of the genomic information. Here, we present an example of a healthy adult woman with a history of recurrent male neonatal losses due to severe respiratory distress who presented to Medical Genetics for evaluation. A family history of additional male neonatal loss was present, suggesting a potential inherited genetic etiology.

Non-Immune Hydrops Fetalis: Do Placentomegaly and Polyhydramnios Matter?: Hydrops With Polyhydramnios and Placentomegaly

Polyhydramnios and placentomegaly are commonly observed in nonimmune hydrops fetalis (NIHF); however, whether their ultrasonographic identification is relevant for prognosis is controversial. We evaluated outcomes of fetal or neonatal death and preterm birth (PTB) in cases of NIHF alone and in those with polyhydramnios and/or placentomegaly (P/PM).

Prenatal Diagnosis of Congenital Diaphragmatic Hernia: Does Laterality Predict Perinatal Outcomes?

Objective The objective of this study was to examine laterality as a predictor of outcomes among fetuses with prenatally diagnosed congenital diaphragmatic hernia (CDH). Methods This is a retrospective cohort study of pregnancies with CDH evaluated at our center from 2008 to 2016 compared cases with right‐sided CDH (RCDH) versus left‐sided CDH (LCDH). The primary outcome was survival to discharge. Secondary outcomes included ultrasound predictors of poor prognosis (liver herniation, stomach herniation, lung area‐to‐head circumference ratio [LHR]), concurrent anomalies, hydrops, stillbirth, preterm birth, mode of delivery, small for gestational age, use of extracorporeal membrane oxygenation, and length of stay. Terminations and stillbirths were excluded from analyses of neonatal outcomes. Results In this study, 157 (83%) LCDH and 32 (17%) RCDH cases were identified. Survival to discharge was similar (64 vs. 66.4%, p = 0.49) with regard to laterality. RCDH had higher rates of liver herniation (90.6 vs. 72%, p = 0.03), hydrops fetalis (15.6 vs. 1.3%, p < 0.01), and lower LHR (0.87 vs. 0.99, p = 0.04). LCDH had higher rates of stomach herniation (69.4 vs. 12.5%, p < 0.01). Rates of other outcomes were similar in univariate analyses. Adjusting for microarray abnormalities, the odds for survival to discharge for RCDH compared with LCDH was 0.93 (0.38‐2.30, p = 0.88). Conclusion Compared with LCDH, fetuses with RCDH had higher rates of adverse ultrasound predictors, but equivalent survival.