US 11,656,234 B2
Method and computer program for predicting bilirubin levels in neonates
Gilbert Koch, Überlingen (DE); Sven Wellmann, Lörach (DE); Marc Pfister, Hilterfingen (CH); Severin Kasser, Basel (CH); and Melanie Wilbaux, Hagenthal le bas (FR)
Assigned to UNIVERSITÄT BASEL, Basel (CH)
Appl. No. 16/651,992
Filed by UNIVERSITÄT BASEL, Basel (CH)
PCT Filed Sep. 27, 2018, PCT No. PCT/EP2018/076325
§ 371(c)(1), (2) Date Mar. 27, 2020,
PCT Pub. No. WO2019/063722, PCT Pub. Date Apr. 4, 2019.
Claims priority of application No. 17194160 (EP), filed on Sep. 29, 2017.
Prior Publication US 2020/0300872 A1, Sep. 24, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 33/72 (2006.01); G06F 17/18 (2006.01); G16H 10/00 (2018.01); G16H 50/20 (2018.01)
CPC G01N 33/728 (2013.01) [G06F 17/18 (2013.01); G16H 10/00 (2018.01); G16H 50/20 (2018.01); Y10T 436/146666 (2015.01)] 15 Claims
 
1. A method of treating physiological jaundice in a neonate, comprising the steps of:
a. detecting and identifying physiological jaundice in a neonate; and
b. exposing the neonate having physiological jaundice to phototherapy to treat the physiological jaundice;
wherein said detecting and identifying comprises calculating a bilirubin level in the neonate and determining that the calculated bilirubin level is higher than a provided maximum bilirubin level, by performing the steps of:
1) acquiring a series of bilirubin levels measured at different time points from the neonate,
2) acquiring a plurality of covariates from the neonate, each covariate comprising an information about a neonatal property, wherein the information comprises one of the following information:
A birth weight, as a continuous covariate,
A gestational age, as a continuous covariate,
A delivery mode, as a categorical covariate, comprising information about whether the neonate was delivered by Caesarean section or by vaginal delivery;
A type of feeding, as a categorical covariate, comprising information about whether the neonate is fed by mother milk or by formula milk;
A received phototherapy, as a categorical covariate, comprising information about whether the neonate has received phototherapy or not in the past and/or will receive phototherapy in the future,
A weight loss compared to the birth weight, as a continuous covariate,
A low birth weight, as a categorical covariate, comprising information about whether the birth weight was below or above a predefined birth weight, wherein the predefined weight is 2500 g;
A respiratory support, as a categorical covariate, comprising information about whether the neonate has received respiratory support after delivery or not,
3) providing a predefined bilirubin model function, wherein the bilirubin model function is configured to describe a time course of the bilirubin level of the neonate,
4) determining a plurality of model parameters of the bilirubin model function, wherein each model parameter is determined from at least one covariate of the plurality of covariates and an associated population model parameter corresponding to a model parameter for a neonate exhibiting average covariates, and
5) obtaining the calculated bilirubin level in the neonate from the acquired series of bilirubin levels and the bilirubin model function with the determined model parameters, wherein the calculated bilirubin level is a bilirubin level of the neonate for a time later than a lastly acquired bilirubin level of the series of bilirubin levels
wherein the bilirubin model function is a rate equation relating a time-varying bilirubin production rate Kprod, with a time-varying bilirubin elimination rate Kelim, and a time-varying phototherapy exposure function PT, wherein the bilirubin production rate Kprod, the bilirubin elimination rate Kelim and the phototherapy exposure function PT comprise the plurality of model parameters.