In pregnancies affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT), placenta-related biomarkers may play an important role in predicting disease severity, according to a prospective cohort study conducted in Norway, with findings published recently in the journal Placenta.
Recognizing that to date, the prediction of FNAIT severity is quite limited, the researchers sought to explore whether dysregulated maternal angiogenic proteins are responsible for certain neonatal outcomes in human platelet antigen (HPA)-1a alloimmunized pregnancies.
Among individuals with FNAIT, parental incompatibility in HPAs is reported, which is accompanied by subsequent maternal sensitization. In fact, the HPA-1a epitope, which is considered to be the target of FNAIT-related antibodies, is expressed on placental tissue. Epitopes are the part of an antigen that is recognized by the immune system.
In pregnancies that are characterized by HPA-1a alloimmunization, lower birth weights and chronic placental inflammation are frequently observed, thus implying that there is a placental component involved in the pathophysiology of FNAIT.
Read more about FNAIT causes and risk factors
FNAIT is depicted by the presence of thrombocytopenia (low platelet counts) in the fetus or newborn, which is initiated by maternal alloantibodies being directed against HPAs located on fetal platelets. Although the feto-maternal incompatibility observed in HPAs among individuals with FNAIT generally arises from paternal antigens, it also can be linked to donor egg or sperm during the process of in vitro fertilization.
Among the White population, incompatibility in the HPA-1a system is the most common trigger of FNAIT. When FNAIT occurs, alloantibodies cross the placenta and may target fetal platelets for destruction. This process causes the fetus or neonate to be at risk for bleeding.
Factors in maternal plasma linked to higher risk of adverse outcomes
In the current analysis, the investigators identified a total of 87 HPA-1a–negative pregnant women from a large prospective study conducted in Poland. Among the 87 pregnant patients, there were 43 HPA-1a–immunized individuals and 44 non-immunized controls.
In participants’ second and third trimesters, measurements of the following factors were obtained from maternal plasma via the use of enzyme-linked immunosorbent assays:
- Placental growth factor (PlGF)
- Soluble fms-like tyrosine kinase-1 (sFlt-1)
- Soluble endoglin (sEng)
The main outcome measures were either classic FNAIT-associated in nature (severe thrombocytopenia, petechiae, ICH); placenta-related in nature (small for gestational age); or a composite variable of both.
Results of the study revealed no significant differences in plasma concentrations of PlGF, sFlt-1, or sEng, nor in the sFlt-1/ PlGF ratio, when immunized and non-immunized pregnant patients were compared. In HPA-1a alloimmunized pregnancies, increasing levels of sFlt-1 in the third trimester were statistically significantly associated with lower neonatal platelet counts.
Moreover, elevated sFlt-1 levels and sFlt-1/PlGF ratio in participants’ third trimester were significantly associated with a higher likelihood of a composite adverse neonatal outcome in alloimmunized pregnancies.
“An anti-angiogenic profile in HPA-1a alloimmunized mothers is associated with a composite adverse neonatal outcome,” the authors highlighted. “This suggests that sFlt-1 and the sFlt-1/PlGF ratio may assist in predelivery risk stratification and clinical management decisions for FNAIT,” they concluded.
