Long-Term Effects of Fetal and Neonatal Alloimmune Thrombocytopenia and Its Antenatal Treatment on the Medical and Developmental Outcomes of Affected Children

ABSTRACT

Alloimmune thrombocytopenia (AIT) is characterized by severe thrombocytopenia, usually diagnosed after birth, which may result in intracranial hemorrhage (ICH) in as many as 20% of cases. The course of AIT typically worsens in subsequent pregnancies. Administration to mother of intravenous gammaglobulin (IVIG) and/or corticosteroids to increase the fetal platelet counts of a subsequent affected fetus is widely used to avoid ICH. The objective of this study was to evaluate the long-term effects of AIT and its antenatal treatment on the medical and developmental outcomes of affected children. Seventy-one pairs of untreated (older) and antenatally treated (younger) siblings with AIT were compared. A medical questionnaire and the Behavioral Assessment System for Children (BASC) were completed over the telephone by mothers. In this sample, birth platelet counts of treated fetuses were significantly higher than those of the untreated fetuses. Treated children were born at significantly lower gestational ages and with significantly lower birthweights than untreated children. No treated child suffered a perinatal ICH compared with 12 untreated siblings. Treated siblings also had fewer vision problems (three versus 14 in the untreated group). Children treated as fetuses received higher scores on the BASC Adaptive Skills Composite than their untreated siblings. The antenatal regimen of IVIG and/or corticosteroids did not affect the results. Children with AIT treated as fetuses had better long-term developmental-behavioral outcomes than their untreated siblings, perhaps because of higher in utero platelet counts. We speculate that platelets may possibly play a role in neurodevelopmental processes in the fetus.

KEYWORDS

Child development - neonatal hematology - platelets

REFERENCES

• 1 Bussel J B, Berkowitz R L, McFarland J G, Lynch L, Chitkara U. Antenatal treatment of neonatal alloimmune thrombocytopenia.  N Engl J Med. 1988;  319 1374-1378
• 2 Lynch L, Bussel J B, McFarland J G, Chitkara U, Berkowitz R L. Antenatal treatment of alloimmune thrombocytopenia.  Obstet Gynecol. 1992;  80 67-71
• 3 Bussel J B, Berkowitz R L, Lynch L et al.. Antenatal management of alloimmune thrombocytopenia with intravenous gammaglobulin: a randomized trail of the addition of low dose steroids to IVIG in fifty-five maternal-fetal pairs.  Am J Obstet Gynecol. 1996;  175 1414-1423
• 4 Reynolds C R, Kamphaus R W. The Behavior Assessment System for Children (BASC). Circle Pines, MN; American Guidance Service (AGS), Inc 1992
• 5 Bussel J B, Zabusky M R, Berkowitz R L, Mcfarland J G. Fetal alloimmune thrombocytopenia.  N Engl J Med. 1997;  337 22-26
• 6 Bussel J B, Skupski D W, McFarland J. Fetal alloimmune thrombocytopenia: consensus and controversy.  J Matern Fetal Med. 1996;  5 281-292
• 7 Bussel J B, Tanli S, Peterson H C. Favorable neurological outcome in 7 cases of perinatal intracranial hemorrhage due to immune thrombocytopenia.  Am J Pediatr Hematol Oncol. 1991;  13 156-159
• 8 Nass R, Ross G S. Complication of the perinatum: The outcome of prematurity. In: Frank Y Pediatric Behavioral Neurology. New York; CRC Press 1996
• 9 Berkowitz R L, Kolb E A, McFarland J G, Wissert M, Primiani A, Bussel J B. Parallel randomized trials of risk-based therapy for fetal alloimune thrombocytenia.  Obstet Gynecol. 2006;  107 91-96
• 10 Birchall J E, Murphy M F, Kaplan C, Knoll H. European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia.  Br J Haematol. 2003;  122 275-288
• 11 Gaddipati S, Berkowitz R L, Lembet A A, Lapinski R, McFarland J G, Bussel J B. Initial fetal platelet counts predict the response to intravenous gammaglobulin therapy in fetuses affected by Pl^A1 incompatibility.  Am J Obstet Gynecol. 2001;  185 976-980
• 12 Radder C M, Roelen D L, Van de Meer-Prins P M, Claas F H, Kanhai H H, Brand A. The immunological profile of infants born after maternal immunoglobulin treatment and intrauterine platelet transfusions for fetal or neonatal alloimmune thrombocytopenia.  Am J Obstet Gynecol. 2004;  191 815-820
• 13 Radder C M, de Haan M J, Brand A, Stoelhorst G M, Veen S, Kanhai H H. Follow up of children after antenatal treatment for alloimmune thrombocytopenia.  Early Hum Dev. 2004;  80 65-76
• 14 Porcelijn L, Folman C C, de Hass M et al.. Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia.  Pediatr Res. 2002;  52 105-108
• 15 Dame C, Sola M C, Fandrey J et al.. Developmental changes in the expression of transcription factors GATA-1, -2 and -3 during the onset of human medullary haematopoiesis.  Br J Haematol. 2002;  119 510-515
• 16 Dame C, Juul S E, Christensen R D. The biology of erythropoietin in the central nervous system and its neurotrophic and neuroprotective potential.  Biol Neonate. 2001;  79 228-235
• 17 Dame C, Wolber E, Freitag P, Hofmann D, Bartmann P, Fandrey J. Thrombopoietin gene expression in the developing human central nervous system.  Brain Res Dev Brain Res. 2003;  143 217-223