Whitington Peter F, Hibbard Judith U
Department of Pediatrics, Feinberg School of Medicine of Northwestern University, 2300 Children's Plaza Box 57, Children's Memorial Hospital, Chicago, IL 60614, USA.
Lancet. 2004;364(9446):1690-8. doi: 10.1016/S0140-6736(04)17356-X.
Neonatal haemochromatosis is a rare disease of gestation that results in severe fetal liver injury. We hypothesised an alloimmune aetiology for the disorder on the basis of its high recurrence rate in sibships. In this study, we assessed the effectiveness in preventing or changing the severity of recurrent neonatal haemochromatosis of administering during pregnancy high-dose intravenous immunoglobulin (IVIG) derived from pooled serum of multiple donors.
Women whose most recent pregnancy ended in documented neonatal haemochromatosis were treated with IVIG, 1 g/kg bodyweight, weekly from the 18th week until the end of gestation in their subsequent pregnancy. The outcomes of treated pregnancies were compared with those of randomly selected previous affected pregnancies for each woman, which were used as historical controls.
15 women were treated through 16 pregnancies. All pregnancies progressed uneventfully and resulted in live babies with normal physical examinations and birthweights that were appropriate for gestational age. 12 babies had evidence of liver involvement with neonatal haemochromatosis: 11 had higher than normal concentrations of serum alpha-fetoprotein and ferritin or serum alpha-fetoprotein alone, including four with coagulopathy (international normalised ratio >1.5), and one had coagulopathy alone. All babies survived with medical or no treatment and were healthy at follow-up within the past 6 months. In analysis on a per-mother basis comparing outcomes of treated gestations with those of randomly selected previous affected gestations, gestational IVIG therapy was associated with better infant survival (15 good outcomes vs two in previous pregnancies; p=0.0009).
Treatment with high-dose IVIG during gestation appears to have modified recurrent neonatal haemochromatosis so that it was not lethal to the fetus or neonate. These results further support an alloimmune mechanism for recurrent neonatal haemochromatosis.
新生儿血色沉着症是一种罕见的妊娠期疾病，可导致严重的胎儿肝损伤。基于该病在同胞中的高复发率，我们推测其病因是同种免疫。在本研究中，我们评估了孕期给予多供体混合血清来源的高剂量静脉注射免疫球蛋白（IVIG）预防或改变复发性新生儿血色沉着症严重程度的有效性。
最近一次妊娠以确诊新生儿血色沉着症告终的女性，在随后的妊娠中，从第18周开始至妊娠结束，每周接受1 g/kg体重的IVIG治疗。将接受治疗的妊娠结局与为每位女性随机选择的既往受影响妊娠的结局进行比较，后者用作历史对照。
15名女性接受了16次治疗性妊娠。所有妊娠均顺利进展，分娩的活产婴儿体格检查正常，出生体重与孕周相符。12名婴儿有新生儿血色沉着症肝脏受累的证据：11名婴儿血清甲胎蛋白和铁蛋白浓度高于正常或仅血清甲胎蛋白浓度高于正常，其中4名有凝血功能障碍（国际标准化比值>1.5），1名仅有凝血功能障碍。所有婴儿均经治疗或未经治疗存活，在过去6个月的随访中均健康。在以每位母亲为基础比较治疗妊娠与随机选择的既往受影响妊娠结局的分析中，孕期IVIG治疗与更好的婴儿存活率相关（15次良好结局 vs 既往妊娠2次；p=0.0009）。
孕期高剂量IVIG治疗似乎改变了复发性新生儿血色沉着症，使其对胎儿或新生儿不再致命。这些结果进一步支持复发性新生儿血色沉着症的同种免疫机制。
