Hemophagocytic Lymphohistiocytosis in Pregnancy: A Case Series and Review of the Current Literature.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that can be fatal in pregnancy. We report two cases of severe HLH that highlight etoposide use in pregnancy. CASE 1: 28-year-old G2P1 with lupus presented at 18 weeks with acute hypoxic respiratory failure, hepatic dysfunction, leukopenia, thrombocytopenia, and elevated ferritin. Bone marrow biopsy confirmed HLH. Etoposide and corticosteroid treatment was initiated per HLH protocol; however clinical status declined rapidly. Fetal demise occurred at 21 weeks and she subsequently suffered a massive cerebral vascular accident. She was transitioned to comfort measures and the patient deceased. CASE 2: 37-year-old G4P3 presented at 25 weeks with fever, acute liver failure, thrombocytopenia, and elevated ferritin. HLH treatment was initiated, including etoposide, and diagnosis confirmed with liver biopsy. Fetal growth restriction was diagnosed at 27 weeks. Delivery occurred at 37 weeks. The neonate was found to be CMV positive despite negative maternal serology. CONCLUSION: The addition of etoposide to corticosteroid use is a key component in HLH treatment of nonpregnant individuals. While this is usually avoided in pregnancy, the benefit to the mother may outweigh the potential harm to the fetus in severe cases and it should be strongly considered.

Pregnancy Outcomes Among Obese Women and Their Offspring by Attempted Mode of Delivery.

OBJECTIVE: To compare maternal and neonatal morbidities among obese women and their offspring by attempted delivery approach. METHODS: We performed a retrospective cohort study of 47,372 obese women at delivery (body mass index 30 or greater) eligible for vaginal delivery who were carrying singleton vertex fetuses at 37 weeks of gestation or greater. Prior cesarean delivery, congenital anomalies, and antepartum stillbirth were exclusion criteria. We analyzed outcomes by attempted delivery route and stratified by parity. The composite maternal outcome included intensive care admission, death, hemorrhage, transfusion, or thromboembolism. The neonatal composite included intensive care unit admission, death, seizure, ventilator use, birth injury, or asphyxia. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were calculated using Poisson regression. RESULTS: Among nulliparous women attempting vaginal delivery (n=15,268), the success rate was 72.6% and among parous women (n=23,426), it was 93.7%. The maternal composite outcome rate was not statistically higher among nulliparous women (7.7% compared with 4.2% [adjusted RR 1.58, 95% CI 0.96-2.59]) but it was among parous women (7.6% compared with 2.5% [adjusted RR 2.45, 95% CI 1.23-4.90]) attempting vaginal delivery related to hemorrhage, blood transfusion, or both. In contrast, the neonatal composite outcome rate was lower in parous women (6.0% compared with 11.6% [adjusted RR 0.65, 95% CI 0.51-0.83]) but not in nulliparous women (10.2% compared with 12.4% [adjusted RR 0.91, 95% CI 0.74-1.12]) parous. CONCLUSION: In obese nulliparous women, attempted vaginal delivery was not associated with increased composite maternal or neonatal morbidity. In obese parous women, attempted vaginal delivery was associated with increased composite maternal morbidity and lower composite neonatal morbidity. LEVEL OF EVIDENCE: II.

Use of cell-free DNA in the investigation of intrauterine fetal demise and miscarriage.

OBJECTIVE: To estimate whether cell-free DNA is present in nonviable pregnancies and thus can be used in diagnostic evaluation in this setting. METHODS: We conducted a prospective cohort study of 50 participants at MedStar Washington Hospital Center, Washington, DC, between June 2013 and January 2014. Included were women with pregnancies complicated by missed abortion or fetal demise. All gestational ages were considered for study participation. Participants with fetal demise were offered the standard workup for fetal death per the American College of Obstetricians and Gynecologists. Maternal blood samples were processed to determine the presence of cell-free DNA, the corresponding fetal fractions, and genetic abnormalities. RESULTS: Fifty samples from nonviable pregnancies were analyzed. The average clinical gestational age was 16.9 weeks (standard deviation 9.2). The mean maternal body mass index was 30.3 (standard deviation 9.1). Seventy-six percent (38/50) of samples yielded cell-free DNA results, that is, had fetal fractions within the detectable range of 3.7-65%. Among the 38, 76% (29) were classified as euploid, 21% (8) as trisomies, and 3% (1) as microdeletion. A cell-free DNA result was obtained more frequently at ultrasonographic gestational ages of 8 weeks or greater compared with less than 8 weeks (87.9% [n=29/33, 95% confidence interval (CI) 72.7-95.2; and 52.9%, n=9/17, 95% CI 31.0-73.8] of the time, respectively, P=.012). Time from demise was not associated with obtaining a result. CONCLUSION: Among nonviable pregnancies, cell-free DNA is present in the maternal plasma with fetal fractions greater than 3.7% in more than three fourths of cases after an ultrasonographic gestational age of 8 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928. LEVEL OF EVIDENCE: III.

Understanding the Limitations of Circulating Cell Free Fetal DNA: An Example of Two Unique Cases.

Circulating cell free fetal DNA (cffDNA) is an effective screening modality for fetal aneuploidy. We report two cases of false positive results. The first case involves a female, with self-reported Down syndrome. CffDNA returned positive for trisomy 18 leading to a maternal diagnosis of mosaicism chromosome 18 with normal fetal karyotype. The second case involves a patient with an anomalous fetal ultrasound and cffDNA positive for trisomy 13. Amniocentesis demonstrated a chromosome 8p duplication/deletion. False positive cffDNA may arise in clinical scenarios where diagnostic testing is clearly indicated. Practitioners should recognize the limitations of cffDNA.