A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy

D. Ware Branch*, Alan M Peaceman, Maurice Druzin, Richard K. Silver, Yasser El-Sayed, Robert M. Silver, M. Sean Esplin, Joseph Spinnato, James Harger

*Corresponding author for this work

Research output: Contribution to journalArticle

271 Citations (Scopus)

Abstract

OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low- dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at ≤12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 ± 1.1 weeks; placebo group, 36.7 ± 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 ± 186.1 g; placebo group; 2604.4 ± 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.

Original languageEnglish (US)
Pages (from-to)122-127
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume182
Issue number1 I
DOIs
StatePublished - Jan 1 2000

Fingerprint

Antiphospholipid Syndrome
Intravenous Immunoglobulins
Placebos
Pregnancy
Aspirin
Heparin
Fetal Development
Obstetrics
Therapeutics
Placental Insufficiency
Neonatal Intensive Care Units
Pre-Eclampsia
Gestational Age
Multicenter Studies
Gravidity
Lupus Coagulation Inhibitor
Anticardiolipin Antibodies
Fetal Distress
Premature Birth
Double-Blind Method

Keywords

  • Antiphospholipid syndrome
  • Intravenous immune globulin
  • Pregnancy

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Branch, D. Ware ; Peaceman, Alan M ; Druzin, Maurice ; Silver, Richard K. ; El-Sayed, Yasser ; Silver, Robert M. ; Esplin, M. Sean ; Spinnato, Joseph ; Harger, James. / A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. In: American Journal of Obstetrics and Gynecology. 2000 ; Vol. 182, No. 1 I. pp. 122-127.
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abstract = "OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low- dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at ≤12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 ± 1.1 weeks; placebo group, 36.7 ± 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 ± 186.1 g; placebo group; 2604.4 ± 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0{\%}; placebo group, 33{\%}) and neonatal intensive care unit admission (intravenous immune globulin group, 20{\%}; placebo group, 44{\%}) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.",
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A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. / Branch, D. Ware; Peaceman, Alan M; Druzin, Maurice; Silver, Richard K.; El-Sayed, Yasser; Silver, Robert M.; Esplin, M. Sean; Spinnato, Joseph; Harger, James.

In: American Journal of Obstetrics and Gynecology, Vol. 182, No. 1 I, 01.01.2000, p. 122-127.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy

AU - Branch, D. Ware

AU - Peaceman, Alan M

AU - Druzin, Maurice

AU - Silver, Richard K.

AU - El-Sayed, Yasser

AU - Silver, Robert M.

AU - Esplin, M. Sean

AU - Spinnato, Joseph

AU - Harger, James

PY - 2000/1/1

Y1 - 2000/1/1

N2 - OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low- dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at ≤12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 ± 1.1 weeks; placebo group, 36.7 ± 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 ± 186.1 g; placebo group; 2604.4 ± 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.

AB - OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen. STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low- dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at ≤12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate. RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 ± 1.1 weeks; placebo group, 36.7 ± 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 ± 186.1 g; placebo group; 2604.4 ± 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant. CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.

KW - Antiphospholipid syndrome

KW - Intravenous immune globulin

KW - Pregnancy

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