Okada Noriki, Sasaki Aiko, Saito Jumpei, Mitani Yusuke, Yachie Akihiro, Takahashi Hironori, Matsubara Shigeki, Tenkumo Chiaki, Tanaka Hirokazu, Hata Toshiyuki, Motomura Kenichiro, Nagasawa Junko, Wada Yuka, Sako Mayumi, Yamaguchi Koshi, Matsumoto Kenji, Nakamura Hidefumi, Sago Haruhiko, Mizuta Koichi
Department of Transplant Surgery, Jichi Medical University, Shimotsuke, Japan.
Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Division of Obstetrics, Tokyo, Japan.
J Matern Fetal Neonatal Med. 2020 Jan;33(1):142-148. doi: 10.1080/14767058.2018.1487940. Epub 2018 Jul 22.
Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited. We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment. Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model. Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000-3000 and 4000-5000 mg/dl, respectively. This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.
新生儿血色病（NH）是一种罕见但严重的疾病，可导致暴发性肝衰竭。母亲所生的婴儿中有NH病史，其后续婴儿中NH的复发率为70-90%。最近，有报道称产前母亲高剂量静脉注射免疫球蛋白（IVIG）治疗对预防NH复发有效。然而，关于这种治疗期间IgG浓度的数据有限。我们报告了日本的经验，并提出了IVIG治疗期间IgG的药代动力学模拟模型。有NH诊断妊娠史的女性从孕中期开始每周接受IVIG治疗，直至妊娠结束。治疗期间频繁收集血清IgG水平，并通过二室模型模拟药代动力学。八次妊娠中有六名女性纳入研究。无人经历严重不良事件。八名婴儿中有三名出现短暂肝功能障碍，但均无需任何治疗。一项模拟研究表明，IVIG治疗期间IgG浓度的估计谷值和峰值水平分别为2000-3000和4000-5000mg/dl。这种治疗预防了日本女性同胞中NH的复发。我们研究了血清IgG浓度的细节，并引入了IVIG治疗期间IgG浓度的新药代动力学模拟模型。
