Jangaard Krista A, Fell Deshayne B, Dodds Linda, Allen Alexander C
Department of Neonatal-Perinatal Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Pediatrics. 2008 Jul;122(1):119-24. doi: 10.1542/peds.2007-0967.
The goal was to study the incidence of kernicterus, developmental delay, autism, cerebral palsy, and hearing loss in infants with peak total serum bilirubin levels of >or=325 micromol/L (>or=19 mg/dL), compared with infants with less-severe or no hyperbilirubinemia, in a population of healthy term and late preterm infants.
Prospectively gathered, standardized, maternal and neonatal data for infants at >or=35 weeks of gestation who were born between January 1, 1994, and December 31, 2000, were extracted from the Nova Scotia Atlee Perinatal Database. Infants with Rh factor isoimmunization, significant congenital or chromosomal abnormalities, or severe peripartum asphyxia were excluded. Comparisons were made on the basis of peak total serum bilirubin levels. Diagnoses were obtained through data linkage with the Medical Services Insurance Database for office visits and the Canadian Institute for Health Information Database for hospital admissions. The registration file provided information allowing calculation of follow-up times, which were determined for each separate outcome. Follow-up periods ranged from 2 to 9 years, with the end point being the first time the diagnostic code was encountered in either database. Cox proportional-hazards regression analyses were used to examine the relationships between outcomes and total serum bilirubin levels.
Of 61238 infants included in the study cohort, 4010 (6.7%) did not have linkage data, which left 56019 infants for analysis. There were no cases of kernicterus and no significant differences in rates of cerebral palsy, deafness, developmental delay, or visual abnormalities between the groups. There were suggestions of associations with attention-deficit disorder in the severe hyperbilirubinemia group and with autism in the combined moderate and severe hyperbilirubinemia group.
There was no increase in adverse effects reported previously to be associated with bilirubin toxicity. Associations with developmental delay, attention-deficit disorder, and autism were observed.
本研究旨在探讨血清总胆红素峰值水平≥325微摩尔/升（≥19毫克/分升）的足月及晚期早产儿，相较于胆红素血症较轻或无胆红素血症的婴儿，其发生核黄疸、发育迟缓、自闭症、脑瘫及听力损失的发生率。
从新斯科舍省阿特利围产期数据库中提取1994年1月1日至2000年12月31日期间出生、孕周≥35周的婴儿的前瞻性收集的标准化母婴数据。排除患有Rh因子同种免疫、严重先天性或染色体异常或严重围产期窒息的婴儿。根据血清总胆红素峰值水平进行比较。通过与医疗服务保险数据库的门诊就诊数据及加拿大卫生信息数据库的住院数据进行数据关联来获取诊断信息。登记文件提供了计算随访时间的信息，针对每个单独结局确定随访时间。随访期为2至9年，终点为在任一数据库中首次出现诊断编码的时间。采用Cox比例风险回归分析来检验结局与血清总胆红素水平之间的关系。
在纳入研究队列的61238名婴儿中，4010名（6.7%）没有关联数据，剩余56019名婴儿用于分析。两组均未出现核黄疸病例，脑瘫、耳聋、发育迟缓或视觉异常的发生率也无显著差异。重度高胆红素血症组提示与注意力缺陷障碍有关联，中度和重度高胆红素血症合并组提示与自闭症有关联。
先前报道的与胆红素毒性相关的不良反应并未增加。观察到与发育迟缓、注意力缺陷障碍和自闭症有关联。
