Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements,JAMA

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Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements
JAMA ( IF 63.1 ) Pub Date : 2020-03-24 , DOI: 10.1001/jama.2020.0837
Sanjiv Harpavat ₁ , Joseph A Garcia-Prats ₂ , Carlos Anaya ₃ , Mary L Brandt ₄ , Philip J Lupo ₅ , Milton J Finegold ₆ , Alice Obuobi ₂ , Adel A ElHennawy ₂ , William S Jarriel ₇ , Benjamin L Shneider ₁

Affiliation

Importance Treating biliary atresia in newborns earlier can delay or prevent the need for liver transplant; however, treatment typically occurs later because biliary atresia is difficult to detect during its early stages. Objective To determine the diagnostic yield of newborn screening for biliary atresia with direct or conjugated bilirubin measurements and to evaluate the association of screening implementation with clinical outcomes. Design, Setting, and Participants A cross-sectional screening study of 124 385 infants born at 14 Texas hospitals between January 2015 and June 2018; and a pre-post study of 43 infants who underwent the Kasai portoenterostomy as treatment for biliary atresia at the region's largest pediatric hepatology center before (January 2008-June 2011) or after (January 2015-June 2018) screening implementation. Final follow-up occurred on July 15, 2019. Exposures Two-stage screening with direct or conjugated bilirubin measurements. In stage 1, all newborns were tested within the first 60 hours of life, with a positive screening result defined as bilirubin levels exceeding derived 95th percentile reference intervals. In stage 2, infants who had a positive screening result in stage 1 were retested at or before the 2-week well-child visit, with a positive screening result defined as bilirubin levels greater than the stage 1 result or greater than 1 mg/dL. Main Outcomes and Measures The primary outcomes of the screening study were sensitivity, specificity, positive predictive value, and negative predictive value based on infants testing positive in both stages. The reference standard was biliary atresia diagnosed at the region's pediatric hepatology centers. The primary outcome of the pre-post study was the age infants underwent the Kasai portoenterostomy for treatment of biliary atresia. Results Of 124 385 newborns in the screening study, 49.2% were female, 87.6% were of term gestational age, 70.0% were white, and 48.1% were Hispanic. Screening identified the 7 known infants with biliary atresia with a sensitivity of 100% (95% CI, 56.1%-100.0%), a specificity of 99.9% (95% CI, 99.9%-99.9%), a positive predictive value of 5.9% (95% CI, 2.6%-12.2%), and a negative predictive value of 100.0% (95% CI, 100.0%-100.0%). In the pre-post study, 24 infants were treated before screening implementation and 19 infants were treated after screening implementation (including 6 of 7 from the screening study, 7 from screening at nonstudy hospitals, and 6 from referrals because of clinical symptoms). The age infants underwent the Kasai portoenterostomy was significantly younger after screening was implemented (mean age, 56 days [SD, 19 days] before screening implementation vs 36 days [SD, 22 days] after screening implementation; between-group difference, 19 days [95% CI, 7-32 days]; P = .004). Conclusions and Relevance Newborn screening with direct or conjugated bilirubin measurements detected all known infants with biliary atresia in the study population, although the 95% CI around the sensitivity estimate was wide and the study design did not ensure complete ascertainment of false-negative results. Research is needed in larger populations to obtain more precise estimates of diagnostic yield and to better understand the clinical outcomes and cost-effectiveness of this screening approach.

中文翻译：

使用直接或结合胆红素测量值对新生儿胆道闭锁进行筛查的诊断率

早期治疗新生儿胆道闭锁可以延迟或防止肝移植的需要；然而，由于胆道闭锁在其早期阶段很难被发现，因此治疗通常发生得较晚。目的通过直接或结合胆红素测量确定新生儿胆道闭锁筛查的诊断率，并评估筛查实施与临床结果的关联。设计、设置和参与者对 2015 年 1 月至 2018 年 6 月期间在德克萨斯州 14 家医院出生的 124 385 名婴儿进行的横断面筛查研究；以及一项针对 43 名在该地区最大的儿科肝病中心在筛查实施之前（2008 年 1 月至 2011 年 6 月）或之后（2015 年 1 月至 2018 年 6 月）接受 Kasai 门肠吻合术治疗胆道闭锁的婴儿的事前研究。最终随访于 2019 年 7 月 15 日进行。暴露直接或结合胆红素测量的两阶段筛查。在第一阶段，所有新生儿在出生后的前 60 小时内接受检测，阳性筛查结果定义为胆红素水平超过衍生的 95% 参考区间。在第 2 阶段，在第 1 阶段筛查结果呈阳性的婴儿在 2 周健康儿童访视时或之前重新检测，阳性筛查结果定义为胆红素水平高于第 1 阶段结果或大于 1 mg/dL . 主要结果和措施筛查研究的主要结果是敏感性、特异性、阳性预测值和阴性预测值，基于婴儿在两个阶段检测为阳性。参考标准是在该地区诊断出的胆道闭锁 s 儿科肝病中心。前后研究的主要结果是接受 Kasai 门肠造口术治疗胆道闭锁的年龄婴儿。结果筛查研究的124 385名新生儿中，49.2%为女性，87.6%为足月，70.0%为白人，48.1%为西班牙裔。筛查确定了 7 名已知的胆道闭锁婴儿，敏感性为 100%（95% CI，56.1%-100.0%），特异性为 99.9%（95% CI，99.9%-99.9%），阳性预测值为 5.9 %（95% CI，2.6%-12.2%），阴性预测值为 100.0%（95% CI，100.0%-100.0%）。在前后研究中，24 名婴儿在筛查实施前接受治疗，19 名婴儿在筛查实施后接受治疗（其中 7 名来自筛查研究，7 名来自非研究医院的筛查，6 因临床症状转诊）。实施筛查后，接受 Kasai 门肠造口术的婴儿年龄明显更小（平均年龄，筛查实施前 56 天 [SD，19 天] vs 筛查实施后 36 天 [SD，22 天]；组间差异，19 天 [ 95% CI，7-32 天]；P = .004)。结论和相关性采用直接或结合胆红素测量的新生儿筛查可检测到研究人群中所有已知的胆道闭锁婴儿，尽管围绕敏感性估计的 95% CI 很宽，并且研究设计不能确保完全确定假阴性结果。需要在更大的人群中进行研究，以获得更精确的诊断率估计，并更好地了解这种筛查方法的临床结果和成本效益。

更新日期：2020-03-24

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