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 PlA1 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
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