Robert J. Kopotic

The pulse oximeter perfusion index as a predictor for high illness severity in neonates

Following the first development in its modern form in 1972 by Takuo Aoyagi [1], pulse oximetry has become invaluable for monitoring oxygenation and pulse rate [4]. A constant amount of light (DC) from the pulseoximeter is absorbed by skin, other tissues, and nonpulsatile blood, while a variable amount of light (AC) is absorbed by pulsating arterial inflow. The pulsatile signal indexed against the non-pulsatile signal and expressed as a percentage (AC/DC · 100) is commonly referred to as the perfusion index (PI). Skin colourimetry is related to illness severity in newborns [2] but its utility as a monitoring tool is partially limited by requiring direct caregiver assessment. As local skin vasoconstriction can be associated with skin colour changes, the usefulness of PI for assessing neonatal illness severity was similarly tested. A prospective study was carried out on 101 inborn or outborn Caucasian neonates (52 males, 49 females; gestational age 34.7±4.0 weeks, range 24.7–41.1 weeks; birth weight 2310±950 g, range 410–4170 g) during the first 24 h after admission. Illness severity was determined using the Score for Neonatal Acute Physiology (SNAP) [5] and the infants were categorised as either high or low severity of illness, defined by the presence of severe neonatal morbidity and/or a 24 h SNAP score >10 [2]. PI values were assessed using a Masimo SET Radical pulse-oximeter (Masimo Corp., Irvine, Calif., USA) with the sensor placed randomly on either foot. After the pulse wave was verified to be artifact-free, the PI values were manually captured by an operator, who was unaware of the infant illness severity group, at least every 0.3 min for a duration of 10.6±2.3 min (95% CI 9.9–11.4 min, range: 10–15 min). SpO2, pulse rate, body (skin and core) temperature, and blood pressure were also measured. Out of a total of 2,571 measurements, 2,546 (99.02%) artifact-free readings were obtained. The higher severity group showed a significantly higher frequency of severe neonatal morbidity (P=0.025), as determined by the presence of at least one of the following: sepsis or pneumonia; bronchopulmonary dysplasia; intraventricular haemorrhage grade 3 or more; periventricular leukomalacia grade 3 or more; retinopathy of prematurity grade 3 or more; and necrotising enterocolitis [2]. Predictive accuracy for identifying newborns with higher severity for different cut-off values of PI, SpO2, and pulse rate was calculated using receiver operating characteristic (ROC) curve [3]. Model calibration was evaluated using v to compare the expected values (according to the classification of infants into two severity categories) with the expected values (according to the SpO2, pulse rate and PI values). According to the predefined criteria, 43 neonates (42.6%) were allocated to the high severity group and 58 to the low severity group. Male to female ratio, gestational age, birth weight, body temperature, mean blood pressure, and use of peripheral vasoconstrictors and vasodilators were not significantly different between the two severity groups (P‡0.50). Mean PI values were 1.54±0.80 (range: 0.22–5.22). Significantly lower PI values (0.86±0.26 versus 2.02±0.70; P<0.0001), lower SpO2 (93.3±5.4% versus 95.1±3.9%, P<0.0001) and higher pulse rate Eur J Pediatr (2002) 161: 561–562 DOI 10.1007/s00431-002-1042-5

Histologic chorioamnionitis and severity of illness in very low birth weight newborns.

Objective: Estimating the risk of in-hospital mortality in the neonatal intensive care unit provides important information for health care providers, and several neonatal illness severity scores have been developed. Histologic chorioamnionitis (HCA) is a known cause of neonatal morbidity and mortality. To date, the relationship between HCA and neonatal illness severity scores has not been rigorously tested. In this study, the relationships among HCA, initial illness severity, and neonatal outcomes were analyzed in very low birth weight (VLBW) newborns admitted to the neonatal intensive care unit. Design: Prospective. Setting: Neonatal intensive care unit. Patients: A total of 116 VLBW inborn infants (gestational age, 28.1 ± 2.82 wks; birth weight, 1009 ± 312 g) were categorized as HCA-positive (n = 67) and HCA-negative (n = 49). Interventions: Placental histology was performed to identify HCA. Illness severity evaluation included several different neonatal illness severity scores—Clinical Risk Index for Babies (CRIB), CRIB-II, Score for Neonatal Acute Physiology-II (SNAP-II), and Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II)—as well as the recording of severe morbidity and in-hospital mortality. Measurements and Main Results: HCA-positive VLBW newborns showed significantly lower gestational age (p < .0001) and birth weight (p = .0010), together with higher CRIB, CRIB-II, SNAP-II, and SNAPPE-II scores at admission to the NICU (p ≤ .0001) and mortality rate (p = .0018) than HCA-negative infants. After adjustment for gender and gestational age in a multivariable logistic regression analysis, HCA was found to be an independent predictor of high illness severity: CRIB > 5 (odds ratio [OR], 21.37; 95% confidence interval [CI], 6.24–73.21); CRIB-II > 10 (OR, 56.17; 95% CI, 6.75–467.2); SNAP-II > 22 (OR, 43.05; 95% CI, 11.9–155.7), and SNAPPE-II > 42 (OR, 48.95; 95% CI, 10.18–235.4) (all p values <.0001). Conclusions: Our findings indicate that HCA is a major predictor of morbidity and mortality in VLBW newborns.

Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome

Background: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date. Aims: Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2. Methods: Fourteen subjects from an LCFS2 kindred (gene carriers, n = 5; non-carriers, n = 9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1–46), and D (1–15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured. Results: LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1–46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1–15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (Dmin: 1.02 (0.03) v 1.07 (0.04); p = 0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1–15): 1.59 (0.12) v 1.47 (0.07); p = 0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p = 0.013) than those of non-carriers. Conclusions: Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.

Oral Mucosal Microvascular Abnormalities: An Early Marker of Bronchopulmonary Dysplasia

An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 ± 2.0 wk; birth weight 850 ± 125 g) and 15 sex- and gestational age–matched infants (nine boys and six girls; gestational age 27.6 ± 2.6 wk; birth weight 865 ± 135 g) were examined on postnatal days 1 and 28. BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population. The lower gingival and vestibular oral mucosa was chosen as the study area. The blood vessel area was determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1–46, D 1–15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops. Infants with BPD showed a significantly lower blood vessel area as well as a higher vascular network complexity (D 1–46, D 1–15, and L-Z) than control subjects (p < 0.0001). Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.