Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: Results of a multicenter, prospective, open-label clinical trial.
OBJECTIVE
The recurrence rate of anti-SSA/Ro-associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB.


METHODS
A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with < or = 20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB.


RESULTS
Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues.


CONCLUSIONS
This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers.
Friedman
Deborah M
DM
New York Medical College, Valhalla, NY, USA.
Llanos
Carolina
C
Izmirly
Peter M
PM
Brock
Brigit
B
Byron
John
J
Copel
Joshua
J
Cummiskey
Karen
K
Dooley
Mary Anne
MA
Foley
Jill
J
Graves
Cornelia
C
Hendershott
Colleen
C
Kates
Richard
R
Komissarova
Elena V
EV
Miller
Michelle
M
Paré
Emmanuelle
E
Phoon
Colin K L
CK
Prosen
Tracy
T
Reisner
Dale
D
Ruderman
Eric
E
Samuels
Philip
P
Yu
Jerry K
JK
Kim
Mimi Y
MY
Buyon
Jill P
JP
D004452:Echocardiography; D005006:Ethnicity; D005260:Female; D005313:Fetal Death / Q000453:epidemiology; D005323:Fetal Monitoring; D006327:Heart Block / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000276:immunology / Q000517:prevention & control*; D008180:Lupus Erythematosus, Systemic / Q000000981:diagnostic imaging / Q000276:immunology; D011247:Pregnancy; D044469:Racial Groups
D016756:Immunoglobulins, Intravenous
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