Association Between Maternal Anti-HPA1a Antibodies and Birth Weight of the Newborn.

When the mother develops antibodies against fetal platelets, fetal and neonatal alloimmune thrombocytopenia (FNAIT) can occur, with intracranial haemorrhage as the most severe complication. The frequency of FNAIT is reported to be 1:1,100 live births. The main immunogenic platelet alloantigen system in the Caucasian population is the human platelet antigen 1 (HPA1). The β3 integrin, housing the HPA1 antigen epitope on platelets, is also found on endothelial cells and invasive trophoblasts. It is therefore conceivable that maternal alloantibodies against the β3 integrin could have a direct effect on development and thereby function of the placenta. The aim of the study was to investigate whether the presence of maternal anti-HPA1a antibodies affects birth weight.

We studied 74 term deliveries (≥ 37 gestational weeks) from HPA1a negative women in Norway during 1995-2008 where anti-HPA1a antibody status during pregnancy and corresponding birth weight were known. Most of the participants were selected from a prospective screening study of HPA1a negative pregnancies. Participants were also recruited from a registry in the National reference laboratory for clinical platelet immunology. The study was approved by the Regional Committee for Medical Research Ethics, North Norway. General data concerning the pregnancy and the neonate were \.{/MAIN;222}recorded. Specific data regarding maternal HPA1a immunization status included anti-HPA1a antibody levels measured during pregnancy and post partum. A linear mixed model was used to analyze the influence of maternal anti-HPA1a antibody level on the newborn birth weight. The dependent variable in the model was birth weight. Maternal age and parity, anti-HPA1a antibody level around 34 weeks of gestation, gestational age at time of delivery, sex of neonate and Apgar scores after 1 and 5 minutes were included as independent variables. All independent variables were classified as covariates with fixed effects. Since birth weights among siblings are not independent observations, the model treated each woman as one subject.

The mean birth weight was 3,050 grams when maternal anti-HPA1a antibodies were detected at any level or time during pregnancy (n= 47, 95% C.I. = 2952-3148). If no maternal anti-HPA1a antibodies were detected during pregnancy, the mean birth weight was 3,622 grams (n= 27, 95% C.I. = 3398-3845).We found a highly significant association between anti-HPA1a antibody levels around gestational week 34 and corresponding birth weight in the mixed model analysis, both when using antibody levels as a dichotomy variable (p = 0.006) and when dividing antibody levels into 3 intervals (no antibody detected, less than 3 IU/ml or more than 3 IU/ml, p = 0.011). Anti-HPA1a antibody level treated as a continuous variable was not significantly associated with birth weight (p = 0.057).

We have demonstrated a significant correlation between the presence and level of maternal anti-HPA1a antibodies during pregnancy and neonatal birth weight. Our findings support the hypothesis that HPA1a alloimmunization affects more than just neonatal platelet counts, and should be considered even a placental disorder.

No relevant conflicts of interest to declare.