BACKGROUND Neonatal alloimmune neutropenia results from maternal alloimmunization to human neutrophil antigens. The alloantibodies involved in neonatal alloimmune neutropenia are against human neutrophil antigens HNA‐1a, HNA‐1b, HNA‐1c, HNA‐1d, HNA‐2, HNA‐3a, HNA‐4a, HNA‐4b, and HNA‐5a; however, to date, antibodies specific to HNA‐3b have not been reported. STUDY DESIGN AND METHODS Blood samples from 10,000 unselected neonates were analyzed, resulting in the selection of 88 neutropenic newborns (neutrophil count <1.5 × 109/L) from 83 mothers (three pairs of twins and one triplet). HNA‐3 genotyping was performed by polymerase chain reaction‐restriction fragment length polymorphism to identify the cases of maternal‐fetal HNA‐3 incompatibility. Serologic studies for detecting maternal HNA‐3 alloantibodies were performed with the granulocyte agglutination test, the white blood cell immunofluorescence test, and a LABScreen Multi‐HNA Kit. RESULTS Genotyping studies identified 13 of 88 (14.8%) instances of maternal‐fetal HNA‐3 incompatibility, with all mothers typed as HNA‐3a/a and neonates typed as HNA‐3a/b. Serologic studies revealed that five of 13 (38.5%) mothers carried anti‐HNA‐3b plus human leukocyte antigen antibodies and that three of 13 (23.1%) mothers had anti‐HNA‐3b without human leukocyte antigen antibodies. CONCLUSION Here, we report the first three cases of neonatal alloimmune neutropenia associated with HNA‐3b antibodies resulting in a neonatal alloimmune neutropenia incidence of one in 3333 live births.

Summary Neonatal alloimmune neutropenia (NAIN) is caused by maternal alloimmunisation to fetal human neutrophil antigens (HNAs). This study investigated maternal HNA/HLA alloantibodies involved with NAIN and identified the frequency of NAIN in Brazilian neonates. Neonatal neutropenia (neutrophil count < 1.5 × 109/L) was investigated in samples from 10,000 unselected neonates, resulting in 88 neutropenic newborns (NBs) and their 83 mothers. Genotyping was performed by PCR‐SSP (HNA‐1/‐4) and PCR‐RFLP (HNA‐3/‐5). Serologic studies were performed by GAT (granulocyte agglutination test), Flow‐WIFT (white blood cells immunofluorescence test) and LABScreen‐Multi‐HNA‐Kit (OneLambda®) (LSM). Neonatal neutropenia was identified in 88/10,000 (0·9%) NBs. Genotyping revealed 60·2% maternal‐fetal HNA incompatibilities (31·8% for HNA‐1; 14·8% for HNA‐3; 15·9% for HNA‐4; 21·6% for HNA‐5). Serologic studies revealed 37·3% of mothers with positive results with at least one technique. The detected anti‐HNA specificities were confirmed in eight positive cases related to HNA‐1/‐3 systems. In cases with maternal‐fetal HNA‐4/‐5 incompatibility, no specific neutrophil alloantibodies were found but anti‐HLA I/II were present. Anti‐HNA‐2 was not identified. This is a large Brazilian study which involved the investigation of antibodies against all five HNA systems in neutropenia cases and showed a frequency of NAIN in 8/10,000 neonates. Among the HNA antibodies identified, we highlight the anti‐HNA‐1d and anti‐HNA‐3b, antibodies unusual in alloimmunised women, and rarely related to NAIN cases.

A retrospective study using an obstetric risk score protocol was applied to a stratified sequential sample of 843 singleton livebirths, occurring in the Royal Hospital for Women, Sydney, over a 12-month period (March, 1985-February, 1986). Data collection included 53 prenatal factors, 41 intrapartum factors and 37 neonatal factors. The study was comprised of 346 women admitted to the hospital birth centre and 497 women admitted to labour ward. In labour ward admitted women there was a significant association between high prenatal scores, high intrapartum scores and high neonatal morbidity scores. Women admitted to the birth centre were subjected to a screening procedure which resulted in low prenatal and relatively low intrapartum risk scores. However, neonatal morbidity scores were similar for both groups. The risk scoring protocol used in this study requires further revision to allow the adequate selection of low risk women delivering infants with a low risk of neonatal morbidity in a low risk obstetric setting.

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