Hemolytic disease of the newborn (HDN) results from maternal IgG antibodies that cross the placenta into the fetal circulation during gestation and cause red blood cell (RBC) destruction. Anemia, hyperbilirubinemia and, in severe cases, hydrops fetalis are well-recognized complications. However, much less is known about the prevalence and outcome of neutropenia as a feature of HDN. This study examined the prevalence and outcome of neutropenia in infants with HDN who were followed in the Pediatric Hematology Clinic at the Children's Hospital of Eastern Ontario (CHEO) during the last 5 years, and also investigates possible risk factors for the development of neutropenia in this setting.
A retrospective chart review was perfomed on all infants with HDN followed in the Pediatric Hematology Clinic at CHEO from April 2005 to May 2010. Neutropenia was defined as a neutrophil count low for patient's age according to laboratory normal values (<1.5×109/L for patients <14 days, <1.0×109/L for patients ≥14 days). Statistical analysis was done using SPSS version 18.0 and a Chi-squared test was used to determine significance. The study was approved by the Research Ethics Board at CHEO.
Seventy-four infants with a diagnosis of HDN were identified during the study time period, of which 69 were evaluable. The male to female ratio was 1:1 and the median gestational age at birth was 38 weeks. Rh antibodies were the most prevalent (48%), followed by ABO incompatibility (42%). No cases of hydrops fetalis were recorded. Fifty-three percent of the infants studied developed some degree of neutropenia, with a median neutrophil count at nadir of 0.56 ×109/L. The mean age at the nadir of the neutropenia was 56 days (range 5–181 days) and the neutropenia lasted a mean of 37 days following the nadir (range 3–153 days). No infectious complications were recorded during the period of neutropenia except for one patient born at 32 weeks of gestational age who had necrotizing enterocolitis and bowel perforation at the onset of the neutropenia. In most instances the neutropenia resolved spontaneously within days, but interestingly, 6 infants subsequently developed chronic neutropenia. Statistical analysis revealed that males with HDN were at a significantly higher risk of developing neutropenia (p=0.022) compared to females, but no statistically significant associations between neutropenia and severity of HDN, antibody specificity, treatment with IVIG or transfusions were found. Not surprisingly, 77% of infants with HDN developed thrombocytosis with a maximum platelet count of 1200 ×109/L, and this was not significantly associated with the development of neutropenia.
This is the largest study to date to determine the prevalence of neutropenia in the context of hemolytic disease of the newborn. Our results demonstrate that neutropenia is a common feature of HDN, regardless of the severity of disease, the treatment received or the antibody specificity. Although its clinical course seems to be benign, careful follow-up of these infants should be undertaken. Given the retrospective nature of the study, possible contributing factors such as maternal conditions of pre-eclampsia, drug exposure or ethnicity were not available. Larger prospective studies should be conducted to learn more about the pathophysiology of this phenomenon and its natural course.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.