Stefanos Mantagos

Transcutaneous Bilirubin Nomogram for Prediction of Significant Neonatal Hyperbilirubinemia

OBJECTIVE: The goal was to develop a predictive nomogram, based on transcutaneous bilirubin (TcB) measurements, for assessment of the risk of significant hyperbilirubinemia in healthy term and near-term neonates. METHODS: A total of 10382 TcB measurements were performed with 2039 healthy neonates (gestational age of ≥35 weeks and birth weight of ≥2000 g), with a BiliCheck bilirubinometer (SpectRx, Norcross, GA), at designated time points between 12 and 120 hours of life. According to their severity, these TcB measurements were selectively cross-checked with a direct spectrophotometric device, and significant hyperbilirubinemia was defined on the basis of the hour-specific threshold values for phototherapy proposed by the American Academy of Pediatrics. With the use of likelihood ratios (LRs), the high- and low-risk demarcators for each designated time were calculated and presented on an hour-specific nomogram. RESULTS: Significant hyperbilirubinemia was documented for 122 neonates (6%). At 24 hours of life, the high-risk zone of the nomogram had 73.9% sensitivity and a positive LR of 12.1 in predicting significant hyperbilirubinemia, whereas the low-risk zone had 97.7% sensitivity and a negative LR of 0.04. At 48 hours, the high-risk zone had 90% sensitivity and a positive LR of 12.1, whereas the low-risk zone had 98.8% sensitivity and a negative LR of 0.02. In our study population, the probability of significant hyperbilirubinemia would be >35% for values in the high-risk zone and <0.5% for values in the low-risk zone of the nomogram. CONCLUSIONS: We provide a predictive TcB tool that could allow for a noninvasive, risk-based approach to neonatal hyperbilirubinemia.

Transcutaneous Bilirubin Levels for the First 120 Postnatal Hours in Healthy Neonates

OBJECTIVE: The objective of this study was to provide data on transcutaneous bilirubin (TcB) levels for the first 120 postnatal hours and to develop an hour-specific TcB nomogram for healthy term and near-term neonates. METHODS: From September 2005 to August 2008, we obtained 14864 TcB measurements from 2818 healthy neonates (gestational age ≥ 35 weeks and birth weight ≥ 2000 g). All measurements were performed with the BiliCheck bilirubinometer, at designated times from 12 to 120 postnatal hours. TcB percentiles for each designated time were calculated and used for the development of an hour-specific nomogram. TcB percentiles for neonates who required phototherapy are also presented. RESULTS: The developed TcB nomogram reflects the natural history of TcB levels in healthy neonates up to the fifth postnatal day. A different pattern of TcB increasing rate was noted in neonates who did and did not require phototherapy but with substantial overlap of TcB values between the 2 groups. CONCLUSIONS: We provide data on TcB levels for the first 120 postnatal hours from a large population of white, healthy, term and near-term neonates. We also present a percentile-based TcB nomogram designated for noninvasive and hour-specific evaluation of neonatal hyperbilirubinemia.

Neonatal cardiac dysfunction in intrauterine growth restriction

Background:The early postnatal cardiovascular consequences of intrauterine growth restriction (IUGR) have not been completely elucidated. This study aimed to evaluate the effect of IUGR on neonatal myocardial function and cardiovascular adaptation to extrauterine life.Methods:Conventional and tissue Doppler echocardiographic parameters were compared on the second and fifth postnatal day between 30 IUGR and 30 appropriate-for-gestational age (AGA) neonates.Results:IUGR neonates presented relative interventricular septum (IVS) hypertrophy (IVS to left ventricular (LV) posterior wall diastolic ratio: median IUGR–AGA difference of 0.05 (interquartile range: 0.04–0.06); P = 0.020), relative LV dilatation (wall thickness to end-diastolic LV dimension difference of 0.12 (0.06–0.16); P = 0.012), and increased left myocardial performance index (MPI difference of 0.19 (0.05–0.28); P = 0.012). Repeated measurements ANOVA revealed a different pattern of change in LV stroke volume (LVSV; P < 0.001), LV cardiac output (LVCO; P < 0.001), MPI (P < 0.001), and heart rate (HR; P = 0.025) between AGA and IUGR infants. From the second to the fifth postnatal day, AGA neonates presented a decrease in MPI and HR with an increase in LVSV and LVCO. IUGR neonates failed to achieve similar changes in MPI, HR, and LVSV, whereas their LVCO decreased.Conclusion:IUGR neonates present changes in cardiac morphology and subclinical myocardial dysfunction, which may result in an altered pattern of cardiovascular adaptation to extrauterine life.

Respiratory muscle function in patients with cystic fibrosis.

Respiratory muscle function in patients with cystic fibrosis (CF) can be assessed by measurement of maximal inspiratory pressure (Pimax), maximal expiratory pressure (Pemax), and pressure–time index of the respiratory muscles (PTImus). We investigated the differences in maximal respiratory pressures and PTImus between CF patients with no gross hyperinflation and healthy controls and described the effects of pulmonary function and nutrition impairment on respiratory muscle function in this group of CF patients. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and maximal expiratory flow between 25% and 75% of VC (MEF25–75), body mass index (BMI), upper arm muscle area (UAMA), Pimax, Pemax, and PTImus were assessed in 140 CF patients and in a control group of 140 healthy subjects matched for age and gender. Median Pimax and Pemax were significantly lower in CF patients compared to the controls [Pimax = 74 (57–94) in CF vs. 84 (66–102) in controls, P = 0.009], [Pemax = 71 (50–95) in CF vs. 84 (66–102) in controls, P < 0.001]. Median PTImus in CF patients compared to controls was significantly increased [PTImus = 0.110 (0.076–0.160) in CF vs. 0.094 (0.070–0.137) in controls, P = 0.049] and it was significantly higher in CF patients with impaired pulmonary function. In CF patients, PTImus was significantly negatively related to upper arm muscle area (r = 0.184, P = 0.031). These findings suggest that CF patients with no severe lung disease compared to healthy subjects exhibit impaired respiratory muscle function, while CF patients with impaired pulmonary function and nutrition indices exhibit higher PTImus values. Pediatr Pulmonol. 2013; 48:865–873.

Periconceptional tobacco smoking and Xisolated congenital heart defects in the neonatal period

BACKGROUND Tobacco use in pregnancy is considered a human developmental toxicant and potential teratogen. The aim of the study was to test for a possible association between periconceptional tobacco smoking and congenital heart disease (CHD) in the neonatal period. METHODS Maternal and infant characteristics of 157 neonates diagnosed with CHD at the University of Patras Medical School were collected and were compared with 208 normal neonates (aged 1-28 days) that were referred for echocardiography during a specified 3-year period. RESULTS In neonates with CHD 64 of 157 mothers (40.8%) reported smoking in pregnancy, whereas in the control group 41 of 208 mothers (19.7%) were smokers (p=0.000). Logistic regression analysis with pregestational diabetes, history of influenza-like illness in the first trimester, therapeutic drug exposure in pregnancy, maternal age, parity, family history of CHD, infant gender, prematurity and paternal smoking, as potential confounding factors showed that periconceptional tobacco smoking was associated with increased risk of CHD in the offspring (OR=2.750, 95% CI=1.659-4.476, p=0.00001). The incidence of neonatal heart disease in women who were non-smokers or smoked 1-10 and ≥11 cigarettes per day increased with the level of fetal tobacco exposure (35.8% versus 55.3% versus 64.3%, x2-test=20.303, p=0.000), suggesting a dose effect. CONCLUSIONS The results of the study are indicative of an association between periconceptional tobacco exposure and increased risk of CHD in the neonatal period. The potential role of gestational smoking as a risk factor for specific heart defect subgroups requires the conduction of large population based epidemiological studies.

Diagnostic role of plasma BNP levels in neonates with signs of congenital heart disease

BACKGROUND Only a few studies have examined the relationship of plasma BNP levels and congenital heart disease (CHD) in neonates and these mainly concern preterm neonates with patent ductus arteriosus. We aimed to investigate the diagnostic role of plasma BNP in neonates admitted in the neonatal intensive care unit, (NICU), with signs of congenital heart disease (CHD). METHODS Prospective assessment of plasma BNP levels in 75 consecutive neonates with suspected CHD (heart murmur, respiratory distress, or cyanosis), admitted in the NICU of our university hospital. The final diagnosis was done with echocardiography. RESULTS Haemodynamically significant Left to Right shunts, (hsLtR), were found in 29 neonates, insignificant LtR shunts in 22, no heart disease in 15 and cyanotic heart disease in 9. BNP levels were significantly higher in neonates with hsLtR shunts vs. all other groups (logBNP 2.9 ± 0.5 pg/ml vs. 1.5 ± 0.4 pg/ml vs. 1.5 ± 0.3 pg/ml vs. 1.6 ± 0.2 pg/ml, p < 0.0001). Plasma BNP levels > 132.5 pg/ml had 93.1% sensitivity and 100% specificity for diagnosing hsLtR shunts (accuracy 99.6%). CONCLUSIONS Plasma BNP is a reliable test for diagnosing hsLtR shunts in the NICU. This will alert the neonatologist for ordering an echocardiographic examination, or if the latter is not available, for transferring the neonate to an appropriate tertiary centre with neonatal-paediatric cardiology facilities. Normal BNP levels imply the absence of a significant LtR shunt, but may not exclude cyanotic heart disease.

Prediction of extubation outcome in preterm infants by composite extubation indices.

Objective: To determine whether composite extubation indices can predict extubation outcome in preterm infants. Design: Prospective observational study. Setting: Level III neonatal intensive care unit. Patients: Fifty-six preterm infants cared for in the neonatal intensive care unit of a tertiary teaching hospital during 2007 and 2008. Interventions: None. Measurements and Main Results: The study consisted of two parts. In the first part, different extubation indices were evaluated in a group of 28 neonates (derivation group). These indices included the diaphragmatic pressure–time index, the respiratory muscle pressure–time index, the maximal transdiaphragmatic pressure, the maximal inspiratory pressure, the airway pressure generated 100 milliseconds after an occlusion/maximal transdiaphragmatic pressure ratio, the airway pressure generated 100 milliseconds after an occlusion/maximal inspiratory pressure ratio, the tidal volume, and the respiratory rate to tidal volume ratio. After exploratory analysis, the best performing indices and the optimal threshold values to predict extubation outcome were selected. In the second part of the study, these indices were validated at the predetermined threshold values in an additional group of 28 preterm neonates (validation group). Four infants (14.3%) in the derivation group and four in the validation group (14.3%) failed extubation. Receiver operator characteristic curve analysis revealed that a diaphragmatic pressure–time index of ≤0.12, a respiratory muscle pressure–time index ≤0.10, a airway pressure generated 100 milliseconds after an occlusion/maximal transdiaphragmatic pressure of ≤0.14, and a airway pressure generated 100 milliseconds after an occlusion/maximal inspiratory pressure of ≤0.09 were the most accurate predictors of extubation outcome in the derivation group. In the validation group, a diaphragmatic pressure–time index of ≤0.12 and a respiratory muscle pressure–time index of ≤0.10 both had zero false-positive results, predicting with accuracy successful extubation. Conclusion: Composite extubation indices such as the diaphragmatic pressure–time index and the noninvasive respiratory muscle pressure–time index can accurately predict extubation outcome in preterm neonates.

Evaluation of potential medical and economic benefits of universal rotavirus vaccination in Greece

Aim:  To evaluate the potential benefits of introducing universal rotavirus (RV) vaccination in Greece.

Congenital heart disease in twins: The contribution of type of conception and chorionicity

BACKGROUND Increased incidence of congenital heart disease (CHD) has been reported in the offspring of monochorionic twin gestations. Assisted reproductive technology (ART), which is related to increased rates of twinning, has also been associated with higher risk of birth defects. We studied the incidence of CHD in a cohort of twins to clarify the contribution of type of conception and chorionicity. METHODS Data concerning 874 live-born twins of which at least one was admitted in our Neonatal Unit during 1995-2012 were analysed. Forty-five % (N=197) of the gestations resulted from ART (in vitro fertilisation or intracytoplasmic sperm insertion). RESULTS In the ART group 32/389 (8.2%) had CHD compared to 21/485 (4.3%) infants conceived naturally (OR 1.90, 95%CI 1.08-3.34, p=0.024). Spontaneous-conception gestations had higher incidence of monochorionic placentation (47/245 versus 4/197, p<0.001), and included younger mothers (29.1±5.2 versus 33.9±5.5years, p<0.001) who had higher parity (median 2 [range 1-7] versus 1 Pinborg (2005), Blondel and Kaminski (2002), Knopman et al. (2014), Kyvik and Derom (2006) ; p<0.001). Multivariable logistic regression analysis showed that ART (OR 2.60, 95% CI 1.24-5.45) and monochorionicity (OR 3.49, 95% CI 1.57-7.77) were significant determinants of CHD, independently of maternal age, parity, and the gender of the offspring. CONCLUSIONS We confirmed that monochorionic twins have increased risk of CHD and we documented a higher incidence of CHD in ART twins independently of chorionicity. We suggest improvement of echocardiographic skills of health care professionals involved in prenatal screening and foetal cardiology referral of ART dichorionic twins with suspicious findings at screening, in addition to all monochorionic gestations.

Burden of rotavirus gastroenteritis in children <5 years of age in Greece: hospital-based prospective surveillance (2008-2010).

Objectives This study describes the epidemiology of rotavirus (RV) gastroenteritis (GE) disease following the introduction of RV vaccination in Greece in 2006. Design A prospective hospital-based surveillance. Setting A multicentre study was conducted at six hospitals in Greece between July 2008 and March 2010. The hospitals selected served 70% of the paediatric population in Greece. Participants Children aged <5 years who visited the emergency rooms (ERs) or hospitalised with acute GE or acquired acute GE 48 h after hospitalisation and with a confirmed RV-positive stool test were enrolled. Primary and secondary outcome measures The occurrence of RVGE among all acute GE ER visits and hospitalisations and the occurrence of nosocomial RVGE are reported with 95% exact CI. Age-specific proportions of RVGE, seasonality and prevalence of RV genotypes were estimated. Incidence rates of nosocomial acute GE and RVGE are expressed in terms of 1000 children-years with 95% exact Poisson CI. Median duration of hospitalisation and prolongation of hospitalisation due to nosocomial RVGE were reported. Results RVGE proportions were 10.7% (95% CI 5.5% to 18.3%) and 23.8% (95% CI 20.0% to 28.0%) of acute GE ER visits and hospitalisations, respectively; and 21.6% (95% CI 9.8% to 38.2%) of nosocomial acute GE cases. The majority of RVGE cases occurred in children aged <24 months (53%). RV infection peaked between December and May (31.4%). The most common RV genotypes were G4 (59.6%) and P[8] (75.2%). The median duration of RVGE hospitalisation was 4 days (range 1–10 days). Incidence of nosocomial RVGE was 0.3 (95% CI 0.2 to 0.7)/1000 children-years. The median prolongation of hospitalisation due to nosocomial RVGE was 5 days (range 4–7 days). Conclusions Our analysis report low proportions of RVGE among acute GE cases in Greece which may be attributable to available RV vaccination in Greece. Future impact/effectiveness studies are necessary to confirm this finding. Clinical Trial Registration NCT00751686.