HLA antibodies in fetal and neonatal alloimmune thrombocytopenia.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antibodies against human platelet antigens (HPA). However, in many cases that meet clinical criteria for the condition, maternal sera do not have HPA antibodies. In studies examining whether human leukocyte antigen (HLA) antibodies cause FNAIT, the results are limited and inconclusive. This study sought to examine whether clinically suspected FNAIT cases with absent maternal HPA antibodies had different HLA antibody strength and specificity compared to controls. STUDY DESIGN AND METHODS: A retrospective case-control study assessed class I HLA antibody strength and specificity in cases submitted for testing to Versiti, Wisconsin. There were 813 cases that met initial screening criteria, but written consent could only be obtained for 50. After review of medical records and expert panel review, 31 cases with clinical criteria of FNAIT and maternal HLA but not HPA antibodies were included. Each case was matched for maternal age, gestational age at delivery, parity, and race/ethnicity to two controls from unaffected pregnancies that had maternal serum HLA antibodies. RESULTS: FNAIT cases were found to have both significantly higher HLA antibody strength, measured by mean fluorescence index (MFI), and broader HLA antibody specificity at antigen epitope level, compared to matched controls (p < .001). p-values remained significant after controlling for parity and gestational age at delivery. DISCUSSION: Additional studies are needed to further examine whether the strong HLA antibodies identified in HPA-antibody-negative cases directly cause neonatal thrombocytopenia and whether prenatal treatment may be warranted in select cases to prevent recurrence.

Maternal anemia and severe maternal morbidity in a US cohort.

BACKGROUND: Maternal anemia is a common pregnancy complication and often leads to a requirement for additional treatments and interventions. Identifying the frequency at which women with antenatally diagnosed anemia experience severe morbidity at the time of admission to the labor and delivery unit will guide future recommendations regarding screening and interventions for anemia during pregnancy. OBJECTIVE: The objective of this study was to evaluate the association between antenatally diagnosed anemia and severe maternal morbidity as defined by the Centers for Disease Control and Prevention in a large, contemporary, US cohort. Neonatal outcomes were also examined. STUDY DESIGN: This was a secondary analysis of the Consortium on Safe Labor database from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which collected data on 228,438 deliveries in 19 United States hospitals from 2002 to 2008. This analysis included women with viable, singleton gestations and excluded stillbirths and gestations with severe congenital anomalies. Women with a diagnosis of antenatal anemia were compared with those without. Identification of diagnoses of antenatal anemia was obtained via electronic medical record abstraction and International Classification of Diseases coding according to each hospital protocol within the Consortium on Safe Labor. The primary maternal outcome consisted of a composite of severe maternal morbidity as defined by the Centers for Disease Control and Prevention and included maternal death, eclampsia, thrombosis, transfusion, hysterectomy, and maternal intensive care unit admission. The primary neonatal outcome was a composite that included a 5-minute Apgar score of <7, hypoxic ischemic encephalopathy, respiratory distress syndrome, necrotizing enterocolitis, seizures, intracranial hemorrhage, periventricular or intraventricular hemorrhage, neonatal sepsis, neonatal intensive care unit admission, and neonatal death. Each outcome within the composites was assessed individually along with other additional secondary outcomes, including a composite of severe maternal morbidity not including transfusion morbidity. All statistical analyses were performed with Stata version 14.2 (StataCorp LLC, College Station, TX) using Student's t test, chi-square test, Fisher's exact test, and Wilcoxon rank-sum (Mann-Whitney U) test, as appropriate. A multivariable logistic regression was performed with potential confounding variables entered into the regression equation if they differed between groups at a significance level of P<.05. RESULTS: A total of 166,566 women met the inclusion criteria. From the original cohort, 56,734 women could not be included because of an unknown diagnosis of anemia. Of those included, 10,217 (6.1%) were diagnosed with anemia during the pregnancy. Women with anemia were more likely to be younger, non-Hispanic Black, single, multiparous, and have a higher prepregnancy body mass index than those without anemia. The frequency of the primary maternal composite outcome, the neonatal composite outcome, and other secondary outcomes including the severe maternal morbidity composite not including transfusion, maternal death, transfusion during labor and the postpartum period, hysterectomy, postpartum hemorrhage, infectious morbidity, cesarean delivery, and preterm delivery were more common in women with anemia (P<.05). After multivariable logistic regression analysis adjusting for confounders, higher rates of severe maternal morbidity remained persistently associated with anemia (adjusted odds ratio, 2.04; 95% confidence interval, 1.86-2.23) in addition to the association of anemia with the severe maternal morbidity composite not including transfusion, maternal death, thrombosis, transfusion, hysterectomy, intensive care unit admission, postpartum hemorrhage, hypertensive disorders of pregnancy, cesarean delivery, and infectious morbidity. The composite neonatal outcome also remained associated with anemia after adjusting for confounders (adjusted odds ratio, 1.14; 95% confidence interval, 1.06-1.23). CONCLUSION: Women with antepartum anemia experienced increased rates of severe maternal morbidity and other serious adverse outcomes. Diagnosis and treatment of anemia during the antepartum period may lead to the identification and treatment of women at higher risk for maternal morbidity and mortality.

Nonimmune Hydrops Fetalis.

Nonimmune hydrops fetalis (NIHF) historically has been considered a lethal fetal condition. Understanding NIHF to be a symptom or an end-stage status of a variety of fetal conditions, along with improved fetal diagnostics and interventions, has changed the landscape for at least some fetuses. Understanding the pathophysiologic mechanisms has led to the development of diagnostic algorithms, improved understanding of cause, and therefore fetal or neonatal treatments. Multidisciplinary counseling and shared decision making are critical to supporting families through pregnancy decisions, potential fetal therapeutic interventions, neonatal management decisions, and at times accepting or transitioning to palliative care.