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.

The effect of GH treatment on serum FGF23 and Klotho in GH-deficient children.

BACKGROUND: Normal phosphate homeostasis is essential for normal linear growth. The phosphaturic fibroblast growth factor 23 (FGF23)/Klotho axis is a major regulator of phosphate homeostasis; therefore, an intact FGF23/Klotho axis is important for normal linear growth. On the other hand, GH/IGF1 axis has opposing effects on phosphate homeostasis, but the underline mechanisms remain unclear. AIM: The main objective of this study was to investigate the possible interactions of FGF23 and its co-receptor Klotho, with growth hormone (GH)/IGF1 axis in the regulation of phosphate metabolism in GH-deficient children under GH treatment. METHODS: We studied 23 GH-deficient children, before and 3 months after the onset of GH treatment. Anthropometry and assessment of biochemical parameters were performed, as well as measurement of FGF23 (intact FGF23/iFGF23 and C-terminal FGF23/cFGF23) and soluble α-Klotho (sKlotho) levels. RESULTS: After 3 months on GH treatment, the elevation of serum phosphate and TmPO4/GFR (P<0.0001 and P<0.01 respectively) was accompanied by a significant increase in cFGF23 (P<0.01), iFGF23 (P<0.0001), sKlotho (P<0.0001) and IGF1 (P<0.0001). Serum phosphate and TmPO4/GFR were positively associated with iFGF23 (P<0.01 and P<0.05) and IGF1 (P<0.05 and P<0.05). iFGF23 levels were positively correlated with sKlotho (P<0.001), IGF1 (P<0.0001) and height SDS (P<0.0001), whereas sKlotho was positively associated with IGF1 (P<0.0001) and height SDS (P<0.001). CONCLUSION: The increase in serum phosphate, which we found in GH-deficient children under GH treatment, is not associated with suppression but rather than with upregulation of the phosphaturic FGF23/Klotho axis.

Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. AIMS: To explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. STUDY DESIGN, SUBJECTS AND OUTCOME MEASUREMENTS: Conventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. RESULTS: IUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E' ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20 ms vs. 36±12 ms, P<0.001; JTd-D2: 54±13 ms vs. 34±9 ms, P<0.001; QTd-D5: 61±14 ms vs. 27±12 ms, P<0.001; JTd-D5: 54±13 ms vs. 27±9 ms, P<0.001). The association between QTd and LV E/E' (D2: regression coefficient beta 0.747, R(2) 0.585; D5: beta 0.843, R(2) 0.646) and QTd and MPI (D2: beta 0.680, R(2) 0.576; D5: beta 0.698, R(2) 0.650) was also significant (P<0.001 for all analyses). CONCLUSIONS: Our findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events.

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.

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.

Rare types of rotaviruses isolated from children with acute gastroenteritis in Patras, Greece.

BACKGROUND: Acute diarrhea remains a major public health issue worldwide, with gastroenteritis agents associated with a high morbidity, especially in infants and young children. A 1-year study (2009-2010) of rotavirus (RV)-caused pediatric diarrhea was performed on hospitalized children admitted with symptoms of acute diarrhea to the University Hospital of Patras, Greece. METHODS: Twenty-nine fecal samples were investigated for RVs, adenoviruses (AdVs), and enteroviruses (EVs) in an attempt to characterize these enteric viruses, which have been implicated in hospitalized diarrhea. RESULTS: A 44.8% (13/29) incidence of viral infection was reported for the viral targets. Monoinfections accounted for 31% (9/29), while bi-infections accounted for 13.4% (4/29). Sequencing of positive samples allowed identification of RVs G4P[8] (2/29), G9P[8] (1/29), and interestingly of the rare type G12P[8] (2/29). AdV types 1, 2, and 6 were also identified in 4/29, 1/29, and 1/29 of the samples, respectively. Regarding the EVs, EV71 (2/29), coxsackievirus A4 (1/29), echovirus 11 (1/29), and EV96 (1/29) were typed. CONCLUSION: The results of the present study, and specifically the detection of rare RV G12 and EV71 strains, address the need for continuous epidemiological surveys to provide epidemiological pictures of pediatric viral infections circulating in the community.

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.

An uncommon case of pediatric neurobrucellosis associated with intracranial hypertension.

We present the case of a 4-year-old boy who was admitted to hospital with intracranial hypertension, headache, diplopia, papilledema, and a normal brain MRI. Brucella melitensis in the cerebrospinal fluid was confirmed with PCR assay. We believe that neurobrucellosis should be included in the differential diagnosis when headaches persist following brucellosis. In addition, we suggest that when cerebrospinal fluid culture is negative, PCR may prove to be an optimal alternative tool for an immediate and accurate diagnosis.

Respiratory distress syndrome (RDS) in premature infants is underscored by the magnitude of Th1 cytokine polarization.

Respiratory distress syndrome (RDS) is a common problem and the leading cause of death in premature infants (PI). The introduction of surfactant treatment for RDS management has lowered mortality and morbidity; nevertheless, some neonates do not improve and are at increased risk of pulmonary hemorrhage. Inflammation, not only local but also systemic, seems to play an important role in the pathogenesis of RDS. To determine whether cytokine patterns characterize RDS and its outcome, we measured type-1 (IL-2, TNF-α, IFN-γ, IL-6) and type-2 (IL-4, IL-5, IL-10, TGF-ß1) serum cytokines of 47 PI with established RDS and a control group of 30 healthy, appropriate for gestational age, full-term neonates. Cord blood samples were obtained at the time of delivery from PI and controls. Venous blood samples were collected from PI who received surfactant treatment and/or developed pulmonary hemorrhage. Significantly elevated cord blood cytokine levels were observed in PI at time of delivery, compared to controls, except for IL-5 and TNF-α levels that were within control range. The type-1/type-2 cytokine ratio was significantly increased in PI vs controls. Neonates who developed pulmonary hemorrhage between 2 and 3 days of life and/or died, presented the strongest Th1 and type-1 cytokine polarization that was mainly due to increased IFN-γ and TNF-α, and decreased TGF-ß1. The majority of these PI were female with very low gestational age. Overall, PI with RDS present a Th1/type-1 cytokine polarization, which persists irrespective of the treatment provided, and is amplified when complications appear. Th1 polarization is associated with poor prognosis.

Supernumerary umbilical vein in a hydropic neonate with hypertrophic cardiomyopathy.

The anomalies of the umbilical vessels are uncommon, with the exception of a single umbilical artery. We report a term female infant with fetal hydrops, hypertrophic cardiomyopathy, and a four-vessel umbilical cord consisting of two umbilical arteries and two umbilical veins. The presence of two veins in the umbilical cord has been attributed to persistence of both the normal left umbilical vein and the caudal part of the right umbilical vein. This fetal vascular pathology has been reported very rarely and may be associated with increased risk of congenital malformations and adverse perinatal outcome.

Accuracy of cardiac auscultation in asymptomatic neonates with heart murmurs: comparison between pediatric trainees and neonatologists.

The aim of this study was to assess whether cardiac auscultation performed by pediatric trainees and neonatologists can reliably distinguish innocent from pathologic heart murmurs in asymptomatic neonates. From January 2008 to April 2009 the pediatric trainees of our institution were requested to refer all asymptomatic neonates with a murmur and classify the murmurs as "innocent," "pathologic," or "possibly pathologic." Prior to echocardiography, each neonate was evaluated by two experienced neonatologists. The echocardiographic studies of 169 neonates were analyzed. Abnormal cardiac anatomy was found in 55 neonates (32.6%). The overall ability of pediatric trainees in identifying congenital heart disease (CHD) was moderate [area under the curve (AUC) = 0.855] and significantly lower compared to neonatologists (AUC = 0.919, p = 0.007). However, at "lower" levels of clinical confidence (i.e., clinical diagnosis of possibly pathologic murmurs), pediatric trainees had good ability in excluding CHD (sensitivity 94.6%; negative likelihood ratio = 0.09). The ability of cardiac auscultation for diagnosing CHD in asymptomatic neonates is limited and dependent on the physician's experience and level of clinical confidence. Echocardiography should remain an option for all neonates with a possibly pathologic murmur.

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. METHODS: A decision analytic model was developed to compare the burden and cost of rotavirus gastroenteritis (RVGE) with and without a universal RV vaccination (88% vaccination coverage) for a cohort of children followed from birth until the age of five. RESULTS: Universal RV vaccination would substantially decrease the RVGE burden on the National Health System by reducing RVGE-related hospitalizations/emergency visits and medical consultations by 83% and 75%, respectively. Total RVGE-related costs was estimated at about 7.6 M€ and would be reduced by 5.9 M€ (-78%) if RV vaccination was introduced. A rapid effect is expected with 76% of cases and 84% of costs avoided would be averted within 2 years postvaccine introduction. The societal benefit would also be significant: total annual number of RVGE cases and parent's lost work days would be reduced by 67% and 78%, respectively. Including indirect costs, the total disease cost reduction would be 9 M€. CONCLUSION: Introduction of universal RV vaccination in Greece could offer considerable medical and economic benefits for the National Health System and society. Potential herd immunity would improve results in favour of vaccination.

Periconceptional tobacco smoking and isolated 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.

Prediction of respiratory failure in late-preterm infants with respiratory distress at birth.

The aim of this study was to evaluate indices of respiratory failure in terms of their ability to predict respiratory impairment and need for ventilatory support in late-preterm neonates with respiratory distress. Arterial blood gas data during the first 12 postnatal hours or until intubation were recorded in 155 neonates with gestational age 34(0/7)-36(6/7) weeks admitted in the NICU with respiratory distress between January 2006 and June 2008. Alveolar-arterial oxygen tension difference (A-aDO(2)), arterial to alveolar oxygen tension ratio (a/A ratio), and partial arterial oxygen tension to inspired oxygen fraction ratio (PaO(2)/FiO(2)) were calculated. Considering the worst single value of each parameter, receiver operating characteristic curve analyses and area under the curve (AUC) comparisons were used to evaluate their predictive performance. Fifty-five neonates (35.5%) required mechanical ventilation. The predictive performances of the maximum A-aDO(2) (AUC 0.97), minimum a/A ratio (AUC 0.95), and minimum PaO(2)/FiO(2) (AUC 0.95) were similar. The A-aDO(2) at a threshold of >200 mmHg proved to be more effective than the other parameters, having excellent positive and negative likelihood ratios of 24.5 and 0.02, respectively. This threshold was achieved by 98.25% of the neonates who developed respiratory failure at a median of 3 h before the ventilatory support to be definitely decided. Composite indices, such as A-aDO(2), a/A ratio, and PaO(2)/FiO(2), can reasonably predict respiratory failure in late-preterm neonates with respiratory distress, allowing for closer monitoring, early medical intervention, or transfer to a level III neonatal unit.

Angiotensin-converting enzyme gene polymorphism and respiratory muscle function in infants.

OBJECTIVE: Angiotensin-converting enzyme (ACE) gene contains a polymorphism consisting of either the presence (I) or absence (D) of a 287-bp fragment. Recent studies have suggested that the I-allele may be associated with superior exercise endurance; respiratory muscle function may be similarly influenced. The pressure-time index of inspiratory muscles (PTImus) is a measure of the load-capacity ratio of the inspiratory muscles. The objective of this study was to determine whether infants homozygous for the I-allele have lower PTImus compared to infants homozygous for the D-allele or heterozygous I/D. PATIENTS AND METHODS: One hundred thirty-two infants were studied. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pi(mean)/Pi(max)) × (T(i)/T(tot)), where Pi(mean) was the mean inspiratory pressure estimated from airway pressure, generated 100 ms after an occlusion (P(0.1)), Pi(max) was the maximum inspiratory pressure and T(i)/T(tot) was the ratio of the inspiratory time to the total respiratory cycle time. Pi(max) was the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort. RESULTS: Infants with I/I genotype had significantly lower PTImus than infants with either D/D or I/D genotypes (P = 0.000007). ACE genotype was significantly related (P = 0.005) to PTImus measurements, independent of other factors that may affect respiratory muscle function. CONCLUSION: These results suggest that an association of ACE genotypes with PTImus measurements may exist in infants.

Determinants of morbidity in late preterm infants.

OBJECTIVE: To assess the effect of selected maternal medical conditions and complications of pregnancy on the risk for morbidity among late preterm neonates. DESIGN: Prospective cohort study. MATERIAL AND METHODS: A total of 548 late preterm neonates (34(0/7) to 36(6/7)weeks' gestation) delivered from August 2006 to July 2009, were included. Information regarding demographics, gestational age, mode of delivery, maternal age and parity, pre-existing medical conditions and complications of pregnancy were obtained and associated with neonatal morbidity, both independently and as joint exposures. Newborn morbidity was defined by combining specific diagnoses, length of hospital stay, and transfer to the Neonatal Intensive Care Unit. RESULTS: Overall, 165 (30.1%) of the late preterm infants suffered from morbidity. The morbidity rates were 16.8% at 36 weeks' gestation, and then approximately doubled from 38.2% at 35 weeks to 59.7% at 34 weeks. The joint effect of gestational age (OR 8.43 for 34 weeks and 3.60 for 35 weeks' gestation), small for gestational age (SGA) (OR 4.18), multiple gestation (OR 3.68) and lack of antenatal steroid administration (OR 4.03), was greater than the independent effect of each of these factors, and greater than additive. Emergency caesarean section (OR 1.43) and antepartum haemorrhage (OR 3.07) were also associated with a significant impact on neonatal morbidity. CONCLUSIONS: The risk for morbidity among late preterm infants, changes with each passing week of gestation. This risk seems to be intensified, when other exposures such as SGA, multiple gestation, emergency caesarean section, lack of antenatal steroid administration and antepartum haemorrhage, are also present.

Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants.

BACKGROUND: Angiotensin converting enzyme (ACE) gene contains a polymorphism, consisting of either the presence (I) or absence (D) of a 287 base pair fragment. Deletion (D) is associated with increased circulating ACE (cACE) activity. It has been suggested that the D-allele of ACE genotype is associated with power-oriented performance and that cACE activity is correlated with muscle strength. Respiratory muscle function may be similarly influenced. Respiratory muscle strength in infants can be assessed specifically by measurement of the maximum inspiratory pressure during crying (Pimax). Pressure-time index of the respiratory muscles (PTImus) is a non-invasive method, which assesses the load to capacity ratio of the respiratory muscles.The objective of this study was to determine whether increased cACE activity in infants could be related to greater respiratory muscle strength and to investigate the potential association of cACE with PTImus measurements as well as the association of ACE genotypes with cACE activity and respiratory muscle strength in this population. METHODS: Serum ACE activity was assayed by using a UV-kinetic method. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pimean/Pimax) x (Ti/Ttot), where Pimean was the mean inspiratory pressure estimated from airway pressure, generated 100 milliseconds after an occlusion (P0.1), Pimax was the maximum inspiratory pressure and Ti/Ttot was the ratio of the inspiratory time to the total respiratory cycle time. Pimax was the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort. RESULTS: A hundred and ten infants were studied. Infants with D/D genotype had significantly higher serum ACE activity than infants with I/I or I/D genotypes. cACE activity was significantly related to Pimax and inversely related to PTImus. No association between ACE genotypes and Pdimax measurements was found. CONCLUSIONS: These results suggest that a relation in cACE activity and respiratory muscle function may exist in infants. In addition, an association between ACE genotypes and cACE activity, but not respiratory muscle strength, was demonstrated.

A novel mutation in the signal transducer and activator of transcription 3 (STAT3) gene, in hyper-IgE syndrome.

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by a highly elevated serum IgE, recurrent staphylococcal skin abscesses and cyst-forming pneumonia. Non-immunological abnormalities, including a distinctive facial appearance, hyperextensive joints, scoliosis, fracture following minor trauma, and the retention of primary teeth are also observed in many patients. Recently, it was shown that heterozygous mutations in signal transducer and activator of transcription 3 (STAT3), can cause autosomal-dominant HIES. Here we identify and characterize a novel mutation in the DNA-binding domain of STAT3 in a patient with hyper-IgE syndrome. Sequence analysis revealed a de novo heterozygous transition of a G-to-A, causing a substitution of a glycine residue for an aspartic acid in the translated sequence (G342D). The patient has normal levels of STAT3, which is able to translocate to the nucleus upon IL-6 stimulation. However, enzyme-linked DNA-protein interaction analysis showed that the G342D mutation affects the binding ability of STAT3 to target DNA sequences. In addition, as shown by qRT-PCR, the mutation abrogates the STAT3-dependent transcription of the retinoid-related orphan receptor gammat (ROR gammat) gene, an indispensable transcription factor for the commitment of naive CD4+ T cells to the Th17 lineage. These data suggest that the novel G342D mutation affects the binding of STAT3 on DNA and the STAT3-dependent expression of ROR gammat mRNA, leading to the HIES phenotype.