ObjectiveTo test the ability of the Ages and Stages Questionnaire, Third Edition (ASQ3) to help identify or exclude neurodevelopmental impairment (NDI) in very preterm-born children at the corrected age of two.MethodsWe studied the test results of 224 children, born at <32 postmenstrual weeks, who had scores on ASQ3 and Bayley Scales of Infant and Toddler Development, Third Edition (BSIDIII) and neurological examination at 22–26 months’ corrected age. We defined NDI as a score of <70 on the cognitive—or motor composite scale of BSIDIII, or impairment on neurological examination or audiovisual screening. We compared NDI with abnormal ASQ3 scores, i.e., < -2SDs on any domain, and with ASQ3 total scores. To correct for possible overestimation of BSIDIII, we also analyzed the adjusted BSIDIII thresholds for NDI, i.e., scores <80 and <85.ResultsWe found 61 (27%) children with abnormal ASQ3 scores, and 10 (4.5%) children who had NDI with original BSIDIII thresholds (<70). Twelve children had NDI at BSIDIII thresholds at <80, and 15 had <85. None of the 163 (73%) children who passed ASQ3 had NDI. The sensitivity of ASQ3 to detect NDI was excellent (100%), its specificity was acceptable (76%), and its negative predictive value (NPV) was 100%. Sensitivity and NPV remained high with the adjusted BSIDIII thresholds.ConclusionThe Ages and Stages Questionnaire is a simple, valid and cost-effective screening tool to help identify and exclude NDI in very preterm-born children at the corrected age of two years.

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PT devices in the Dutch NICUs show considerable variability with often too low irradiance levels. These results indicate that suboptimal PT is frequently applied and may even be ineffective towards reducing total serum bilirubin levels. These results underline the need for greater awareness among all healthcare workers towards the requirements for effective PT including measurements of irradiance and distance.

Background and ObjectiveHigh bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.MethodsIn a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.ResultsComposite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.ConclusionsThe additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Trial RegistrationControlled-Trials.com ISRCTN74465643

Unconjugated hyperbilirubinaemia occurs in almost all premature infants and is potentially neurotoxic. Treatment is based on total serum bilirubin (TSB), but treatment thresholds are not evidence based. Free bilirubin (Bf)-that is, not bound to albumin, seems a better parameter for bilirubin neurotoxicity, but measurements of Bf are not available in clinical practice. The bilirubin/albumin (B/A) ratio is considered a surrogate parameter for Bf and an interesting additional parameter in the management of hyperbilirubinaemia. This paper reviewed the evidence supporting the use of B/A ratios for predicting bilirubin-induced neurological dysfunction (BIND) including neurodevelopmental delay in jaundiced premature infants (gestational age less than 32 weeks). A literature search was performed and six publications reviewed regarding B/A ratios in the management and outcome of jaundiced premature infants. No prospective clinical trials had been undertaken to show whether bilirubin-induced neurotoxicity is reduced or whether unnecessary treatment is avoided by using the B/A ratio in addition to TSB. Recently, a randomised controlled trial evaluating the effect of the additional use of the B/A ratio on neurodevelopmental outcome in jaundiced premature infants has been initiated. Based on the prevailing evidence many authorities suggest that the additional use of the B/A ratio may be valuable when evaluating jaundiced premature infants.

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Accurate and precise bilirubin and albumin measurements are essential for proper management of jaundiced neonates. Data hereon are lacking for Dutch laboratories. We aimed to determine variability of measurements of bilirubin and albumin concentrations typical for (preterm) neonates. Aqueous, human serum albumin-based samples with different concentrations of bilirubin (100, 200, 300, 400, and 500 μmol/L) and albumin (0, 10, 15, 20, 25, and 30 g/L) were sent to laboratories of all Dutch neonatal intensive care units (n = 10). Bilirubin and albumin recoveries of the specimens were measured using locally available routine analytical methods. The mean, standard deviation, and coefficients of variations (CV) were calculated per sample. Bilirubin concentrations were underestimated in the absence of albumin (maximal CV 26.0%). When the albumin concentration was 10 or 20 g/L, the bilirubin concentrations of the samples were overestimated (maximal CV 14.1% and 9.2%, respectively). Variability increased with higher weighed-in bilirubin concentrations. Measured albumin levels were ~10% lower than albumin levels of manufactured samples. Bilirubin concentration did not influence albumin measurements. The maximal CV was 6.8%. In conclusion, interlaboratory variability of bilirubin and albumin measurements is high. Recalibration and introduction of a specific quality assessment scheme for neonatal samples is recommended to ensure exchangeability of bilirubin and albumin measurements among laboratories and to control the observed large variability.

Background:The relation between total serum bilirubin (TSB) and neurodevelopmental outcome in preterm infants is unclear. Free bilirubin (Bf) and the bilirubin/albumin (B/A) ratio may be more reliable predictors of bilirubin neurotoxicity than TSB, but prospective data regarding neurodevelopmental outcome are lacking.