Dear Editor,

We read with great interest the review by Dorling et al [1]. on neonatal illness severity score systems (NISS), in which the authors have thoroughly examined the strengths and weaknesses of the existing methods. We would like to add a few points to the ongoing debate [2] on the usefulness and limitations of the NISS.

Assessment of illness severity in the newborn is of paramount importance, especially in neonatal intensive care unit (NICU) environment, certainly justifies the ongoing efforts in the search for easy-to-use, reproducible, and accurate methods. Potential limitations may arise from the concepts on which the currently available methods are based.

Firstly, it should be noted that treatment modalities could not only influence neonatal outcomes, as indicated by the report of increased mortality odds among inborn infants 32 weeks' gestation admitted to NICUs at night compared with during daytime [3], but also the relationship between NISS and neonatal morbidity and mortality. To this regard, we have recently shown that CRIB and CRIB-II scores have similar accuracy values in predicting in-hospital neonatal mortality in a population of VLBW infants and that neither score offers an advantage in predicting mortality compared to gestational age or birth weight when applied to a minimal intubation policy NICU setting [4]. The potential relevance of these findings, far from being interpreted as a specific criticism to the CRIB scores, is that treatment modalities can modify both predictive accuracy of illness severity scores and neonatal outcomes.

Secondly, the potential effects of perinatal conditions on postnatal disease severity should be taken into account. For instance, histologic chorioamnionitis (HCA) is a major challenge in perinatology, often subclinical and associated with high rates of preterm birth leading to fetal/neonatal morbidity and mortality [5]. HCA is likely to be mediated by a fetal inflammatory response syndrome, and can be considered a natural model for neonatal illness severity in high-risk newborns [6]. Our group has recently demonstrated that, after adjustment for potential confounders in a multivariable logistic regression analysis, HCA is an independent predictor of high illness severity in very low birth weight infants [7].

Thirdly, and most important, it should be noted that the calculation of a risk assigned to a measured score is an epidemiologic tool, and never should be used as a single patient prevision tool [8]. As a consequence, there is urgent need for new, non-invasive, accurate, and real time risk- adjustment indices of neonatal illness severity, based on different concepts. We have previously reported on the potential value of skin colorimetry [9,10], skin spectrophotometry [11], and pulse oximetry- derived perfusion index [12] in identifying higher-severity newborns. Emerging evidence indicates that the dynamic analysis of heart rate (R-R) variability provides relevant information and is applicable to the health status assessment in a neonatal population [13, 14].

Several homeostatically controlled systems show nonrandom, nonperiodic, systematic variations in time. This is likely to be related to the fact that, in living organisms, essential natural rhythms should maintain sufficient regularity to preserve function and sufficient flexibility in stress adaptation. We have applied a nonlinear dynamic (NLD) approach, based on the chaos theory, to real-time monitoring of pulse oximetry-derived signals, and our preliminary results indicate the occurrence of an early loss in chaotic behaviour for pulse-to-pulse and perfusion index variability in newborns with higher illness severity [15].

Moreover, recent evidence suggests the feasibility of a methodology based on NLD analysis of fetal heart rate, and found to be helpful in identifying pathological states [16]. These data suggest:
(i) the importance of an integrated obstetric-neonatological approach to the issue of neonatal illness severity, with a particular emphasis toward a better understanding of illness severity already in the fetus;
(ii) and the need for novel, real-time indices, which should enable the neonatologist to identify higher-severity newborns, monitoring the evolution of their health status, and possibly applying potential preventive and/or specific therapeutic strategies.

References

(1). Dorling JS, Field DJ, Manktelov B Neonatal disease severity score systems. Arch Dis Child Fetal Neon Ed 2005;90 F11-F16

(2). Meadow W, Frain L, Ren Y, et al. Serial assessment of mortality in the neonatal intensive care unit by algorithm and intuition: certainty, uncertainty, and informed consent. Pediatrics 2002;109:878-86.

(3). Lee SK, Lee DS, Andrews WL, Baboolal R, et al.; Canadian Neonatal Network. Higher mortality rates among inborn infants admitted to neonatal intensive care units at night. J Pediatr 2003;143:592-7.

(4). De Felice C, Del Vecchio A, Latini G. Evaluating illness severity for very low birth weight infants: CRIB or CRIB-II? J Mat Fet Neon Med. In press.

(5). Hagberg H, Wennerholm UB, Savman K. Sequelae of chorioamnionitis. Curr Opin Infect Dis 2002;15:301-6

(6). Gomez R, Romero R, Ghezzi F, et al. The fetal inflammatory response syndrome Am J Obstet Gynecol 1998;179:194-202

(7). De Felice C, Toti P, Parrini S, et al. Histologic chorioamnionitis and severity of illness in very low birth weight newborns. Pediatr Crit Care Med. In press.

(8). Lemeshow S, Le Gall JR. Modeling the severity of illness of ICU patients. A systems update. JAMA. 1994;272:1049-55

(9). De Felice C, Flori ML, Pellegrino M, et al. Predictive value of skin color for illness severity in the high-risk newborn. Pediatr Res. 2002;51:100-5.

(10). De Felice C, Vacca P, Del Vecchio A, et al. Early postnatal skin colour changes in term newborns with subclinical histologic chorioamnionitis. Eur J Pediatr. 2004;163(9):550-4.

(11). De Felice C, Mazzieri S, Pellegrino M, et al. Skin reflectance changes in preterm infants with patent ductus arteriosus. Early Hum Dev 2004;78:45 -51.

(12). De Felice C, Latini G, Vacca P, et al. The pulse oximeter perfusion index as a predictor for high illness severity in neonates. Eur J Pediatr 2002;161:561-562.

(13). Griffin MP, O'Shea TM, Bissonette EA, et al. Abnormal heart rate characteristics are associated with neonatal mortality. Pediatr Res 2004;55:782-8.

(14). Griffin MP, O'Shea TM, Bissonette EA, et al. Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness. Pediatr Res. 2003;53:920-6.

(15). De Felice C, Bianciardi, G, Parrini S, et al. Pulse oximetry signals chaotic analysis in the evaluation of neonatal illness severity. Pediatr Res 2004;56:475.

(16). Signorini MG, Magenes G, Cerutti S, Arduini D. Linear and nonlinear parameters for the analysis of fetal heart rate signal from cardiotocographic recordings. IEEE Trans Biomed Eng 2003;50:365-74.