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.

Phagocytic ability of neutrophils and monocytes in neonates.

BACKGROUND: Infections by a variety of pathogens are a significant cause of morbidity and mortality during perinatal period. The susceptibility of neonates to bacterial infections has been attributed to immaturity of innate immunity. It is considered that one of the impaired mechanisms is the phagocytic function of neutrophils and monocytes. The purpose of the present study was to investigate the phagocytic ability of neonates at birth. METHODS: The phagocytic ability of neutrophils and monocytes of 42 neonates was determined using the Phagotest flow cytometry method, that assesses the intake of E. Coli by phagocytes, in cord blood and in peripheral blood 3 days after birth. Fifteen healthy adults were included in the study as controls. RESULTS: The phagocytic ability of neutrophils in the cord blood of neonates was significantly reduced compared to adults. The 3rd postnatal day the reduction of phagocytic ability of neutrophils was no longer significant compared to adults. The phagocytic ability of monocytes did not show any difference from that of adults either at birth or the 3rd postnatal day. CONCLUSIONS: Our findings indicate that the intake of E. Coli by phagocytes is impaired at birth in both preterm and full term neonates compared to adults. This defect is transient, with the phagocytic ability in neonates reaching that of the adults 3 days after birth.

Intrauterine growth restriction as a potential risk factor for disease onset in adulthood.

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease, type 2 diabetes mellitus, and obesity in adulthood. Several studies on diverse geographic and ethnic cohorts have provided evidence that being born small for gestational age (SGA) increases adult disease risk through various pathways of metabolic dysregulation. Unfavorable influences in the fetal environment may program metabolic homeostasis in later life affecting blood pressure, glucose tolerance and lipid regulation. Fetal restricted protein supply may impair the development of the kidney and reduce the nephron number, which is involved in blood pressure regulation. Moreover, children exposed to IUGR may exhibit postnatal rapid catch-up growth, altered body composition, increased visceral adiposity and low adiponectin levels which predispose to cardiovascular disease and type 2 diabetes mellitus in adulthood. Impairment in fetal pancreatic development and subsequent insulin signalling deficits due to IUGR may also be involved in the pathogenesis of these conditions. This review summarizes some of the hypotheses that have been put forward to explain the association between fetal growth restriction and subsequent metabolic dysregulation that may increase adult disease risk.

Effect of prenatal tobacco smoke exposure on fetal growth potential.

AIM: to determine the independent effect of prenatal tobacco smoke exposure on fetal growth using customized birthweight norms. METHODS: demographic characteristics and data on exposure to tobacco smoke during pregnancy were obtained from singleton neonates ≥ 34 weeks' gestation. Centile Calculator software v62.2 (www.gestation.net) was used for calculating customized birthweight percentiles. RESULTS: of the 3227 neonates studied, 30.9% were exposed to maternal smoking during pregnancy, whereas involuntary maternal exposure was reported in 20.1%. Growth restriction was noted in 350 (10.8%). The odds ratio (OR) for fetal growth restriction was 1.49 (1.10-1.91) in passive smokers, and 2.34 (1.81-2.96) in smokers. A decrease in birthweight and an increase in the prevalence of growth restriction with the increasing number of cigarette consumption was observed. This effect was evident even in cases of a "minimal" consumption of 1-5 cigarettes per day. CONCLUSION: an essential adverse effect of tobacco smoke exposure on fetal growth in pregnancies exposed to passive smoking, as well as in those with "minimal" maternal cigarette consumption, was found. Since approximately 30% of growth restricted neonates could be independently attributed to active or passive maternal exposure, these findings reinforce the need for smoking preventive strategies in pregnant women and their environment.

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.

Impact of maternal smoking on birth size: effect of parity and sex dimorphism.

BACKGROUND: Maternal smoking during pregnancy causes a delay of intrauterine growth. OBJECTIVE: To examine the effect of maternal smoking during pregnancy on fetal growth in relationship to maternal parity, age and number of cigarettes smoked/day, and offspring's gender. SUBJECTS: We studied 2,108 term newborns (1,102 male, 1,006 female) delivered at the General University Hospital of Patras from 1994 to 2004. The 1,443 were born to mothers who did not smoke and 665 to mothers who smoked during pregnancy. METHODS: Birth weight, length and head circumference were measured prospectively in all newborns. Also, maternal smoking status and number of cigarettes smoked per day, age, and parity were recorded. For the analysis, t test, one-way ANOVA, Mann-Whitney U test, Spearman rank correlation, and factorial MANOVA with covariates were used. RESULTS: With increasing parity, in the neonates of nonsmoking mothers there was a gradual increase of growth, whereas in neonates of smoking mothers there was a gradual decrease of growth. This effect was more pronounced in males. A significant negative main effect on growth resulted from the interaction of smoking with parity (p = 0.013), and with gender and parity (p = 0.001). There was a significant negative correlation between number of cigarettes smoked per day and growth, the strength of which increased with parity, mainly in males. CONCLUSION: Maternal smoking during pregnancy causes a delay in fetal growth, which is greater in male offspring, an effect that is enhanced with parity but is independent of maternal age.

Effect of maternal smoking on cord blood estriol, placental lactogen, chorionic gonadotropin, FSH, LH, and cortisol.

AIM: To determine the effect of maternal cigarette smoking on cord blood concentrations of E3, hPL, beta-hCG, FSH, LH, and cortisol. METHODS: Hormone concentrations were measured in term neonates of 100 smoking and 100 non-smoking mothers. RESULTS: The median E3, hPL, beta-hCG, FSH, LH and cortisol cord blood concentrations in the non-smoking mothers' offspring were 212 ng/mL, 2.00 microg/mL, 57.5 mIU/mL, 0.10 mIU/mL, 0.20 mIU/mL, and 14.3 microg/mL, respectively; in the smoking they were 163, 1.39, 45.4, 0.10, 0.20, and 25.1, respectively (P=0.008, 0.004, 0.037, 0.498, 0.286, 0.004, respectively). There was a significant but poor negative correlation between number of cigarettes/day and E3 (r=-0.163, P=0.021), hPL (r=-0.191, P=0.007), and beta-hCG (r=-0.143, P=0.044), whereas the correlation with cortisol was positive (r=0.259, P<0.0001). Multiple linear regression analyses showed that maternal smoking is a determinant of cord blood E3, hPL, beta-hCG, FSH, and cortisol concentrations. CONCLUSIONS: Tobacco smoking is associated with a reduction in cord blood E3, hPL, and beta-hCG concentrations, whereas it is associated with increased cortisol concentrations. The disturbed endocrine equilibrium of the fetus induced by tobacco smoking could have adverse consequences on the fetus and child since fetal brain is a target organ for hormonal actions.

Course of growth during the first 6 years in children exposed in utero to tobacco smoke.

OBJECTIVES: Postnatal growth in children exposed in utero to tobacco smoke is not well understood. This study investigated growth during the first 6 years in children whose mothers smoked during pregnancy. MATERIALS AND METHODS: Weight, length, and head circumference were measured annually for 6 years in 100 children in each group of smoking (study) and nonsmoking (control) mothers. RESULTS: Weight and head circumference were significantly smaller in the neonates whose mothers smoked >or=15 cigarettes/day, but the difference disappeared by 3 years of life. Length was significantly smaller in the study neonates at birth, followed by increasing divergence from normality up to 2 years, when the mean difference of children whose mothers smoked >or=15 cigarettes/day from control children was -3.4 cm (p

Increased cortisol concentrations in the cord blood of newborns whose mothers smoked during pregnancy.

AIM: To investigate the effect of tobacco smoke on cord blood cortisol concentrations. METHODS: Cortisol concentrations were measured in cord blood from 211 term newborns of smoking and 211 term newborns of nonsmoking mothers; 48 and 36 newborns were delivered by cesarean section, respectively. In 16 cases, in addition to cord blood, maternal venous blood was obtained at delivery. RESULTS: The median cord blood cortisol concentration in neonates of the smoking and the nonsmoking mothers was 23 and 13 microg/dL, respectively (P<0.0001). Cortisol concentrations were greater in the newborns whose mothers smoked, when compared to corresponding controls, whether they were delivered vaginally or by cesarean section. In the newborns delivered by cesarean section, there was a positive correlation between number of cigarettes smoked/day and cortisol concentrations, as well as a negative correlation between cortisol concentrations and neonatal length. There was no significant correlation between cortisol concentrations and birth weight or head circumference. Cortisol concentrations in the cord blood of neonates whose mothers were smokers and nonsmokers were by 29% and 45% lower from those measured in their mothers, respectively. CONCLUSIONS: Although a causal relationship between maternal smoking and high cortisol concentrations in cord blood was not established, the findings are in accordance with previous reports indicating elevated stress-hormones in newborns whose mothers smoked during pregnancy.