Department of Neurology, University of California, San Francisco2Department of Pediatrics, University of California, San Francisco.
Department of Pediatrics, University of California, San Francisco3Division of Research, Kaiser Permanente Northern California, Oakland.
JAMA Pediatr. 2015 Mar;169(3):239-46. doi: 10.1001/jamapediatrics.2014.3036.
Exchange transfusion is recommended for newborns with total serum bilirubin (TSB) levels thought to place them at risk for cerebral palsy (CP). However, the excess risk for CP among these infants is unknown.
To quantify the risks for CP and CP consistent with kernicterus that are associated with high TSB levels based on the 2004 American Academy of Pediatrics exchange transfusion threshold (ETT) guidelines.
DESIGN, SETTING, AND PARTICIPANTS: We enrolled 2 cohorts from a population of 525,409 infants in the Late Impact of Getting Hyperbilirubinemia or Phototherapy (LIGHT) birth cohort. Eligible infants were born at a gestational age of at least 35 weeks at 15 hospitals within the Kaiser Permanente Northern California integrated medical care delivery system from January 1, 1995, through December 31, 2011.
The exposed cohort included all 1833 infants with at least 1 TSB measurement at or above the ETT based on age at testing, gestational age, and results of direct antiglobulin testing. The unexposed cohort was a 20% random sample of 104 716 infants with TSB levels below the ETT.
A pediatric neurologist blinded to the TSB levels reviewed medical records to determine the presence of CP, defined as a nonprogressive congenital motor dysfunction with hypertonia or dyskinesia. Cerebral palsy was judged to be consistent with kernicterus if magnetic resonance imaging of the brain revealed bilateral globus pallidus injury in the setting of dyskinetic CP.
We identified CP in 7 of 1833 exposed (0.4%) vs 86 of 104 716 unexposed (0.1%) infants (relative risk, 4.7 [95% CI, 2.2-10.0]). Absolute risk differences were 0.2% (95% CI, 0%-0.5%) for a TSB level 0 to 4.9 mg/dL above the ETT (n = 1705), 0.9% (95% CI, 0.1%-5.3%) for a TSB level 5.0 to 9.9 mg/dL above the ETT (n = 102), and 7.6% (95% CI, 2.1%-24.1%) for a TSB level 10 mg/dL or more above the ETT (n = 26). Cerebral palsy consistent with kernicterus occurred in 3 infants (incidence, 0.57 per 100,000 births); all 3 had TSB levels of more than 5.0 mg/dL above the ETT and at least 2 risk factors for neurotoxicity, such as prematurity, glucose-6-phosphate dehydrogenase deficiency, or hypoxia-ischemia.
Cerebral palsy consistent with kernicterus occurred only in infants with 2 or more risk factors for neurotoxicity and TSB levels of more than 5 mg/dL above the ETT. Among infants with lower degrees of TSB level elevation, the excess risk for CP is minimal.
对于总血清胆红素（TSB）水平被认为使新生儿有脑瘫（CP）风险的新生儿，建议进行换血治疗。然而，这些婴儿中 CP 的额外风险尚不清楚。
根据 2004 年美国儿科学会换血阈值（ETT）指南，量化与高 TSB 水平相关的 CP 和 CP 与 kernicterus 一致的风险。
设计、设置和参与者：我们从 LIGHT 出生队列的 525409 名婴儿中招募了两个队列，这是一个人群队列。合格的婴儿在北加州 Kaiser Permanente 综合医疗保健系统的 15 家医院中，至少在 35 周的胎龄出生，胎龄在 1995 年 1 月 1 日至 2011 年 12 月 31 日之间。
暴露队列包括所有 1833 名 TSB 测量值至少为 ETT 的婴儿，根据测试时的年龄、胎龄和直接抗球蛋白试验结果。未暴露队列是 TSB 水平低于 ETT 的 104716 名婴儿的 20%随机样本。
一名对 TSB 水平盲的儿科神经科医生审查了医疗记录，以确定 CP 的存在，CP 定义为非进行性先天性运动功能障碍，伴有张力亢进或运动障碍。如果大脑磁共振成像显示在运动障碍性 CP 的背景下双侧苍白球损伤，则认为 CP 与 kernicterus 一致。
我们在 1833 名暴露婴儿中发现了 7 例（0.4%）CP，而在 104716 名未暴露婴儿中发现了 86 例（0.1%）（相对风险，4.7 [95%CI，2.2-10.0]）。绝对风险差异为 TSB 水平比 ETT 高 0 至 4.9mg/dL 的 0.2%（95%CI，0%-0.5%）（n=1705），TSB 水平比 ETT 高 5.0 至 9.9mg/dL 的 0.9%（95%CI，0.1%-5.3%）（n=102），以及 TSB 水平比 ETT 高 10mg/dL 或更高的 7.6%（95%CI，2.1%-24.1%）（n=26）。3 例婴儿发生脑瘫合并 kernicterus（发病率，每 10 万例活产 0.57 例）；所有 3 例 TSB 水平均高于 ETT 5.0mg/dL，且至少有 2 个神经毒性危险因素，如早产、葡萄糖-6-磷酸脱氢酶缺乏或缺氧-缺血。
只有在 TSB 水平高于 ETT 5.0mg/dL 且有 2 个以上神经毒性危险因素的婴儿中才会发生脑瘫合并 kernicterus。在 TSB 水平升高程度较低的婴儿中，CP 的额外风险极小。
