Migration status and perinatal parameters in a Greek public maternity hospital: an illustration of the "healthy immigrant effect".

BACKGROUND: Although socioeconomic disparities adversely affect health, studies referring to the "healthy immigrant effect" imply more favorable health outcomes in immigrants than natives. We aimed to investigate the impact of immigration on several perinatal parameters. METHODS: Birth records (01/01/2010 - 31/12/2014) from a public maternity hospital in Athens, Greece were reviewed for maternal (ethnicity, age, delivery mode) and neonatal (gender, birthweight, gestational age) variables. Immigrants were classified by country of origin, according to Human Development Index. Comparison of results between Greeks and immigrants were made. Stratification by maternal age (< and ≥35 years) was conducted to test for confounding and interaction. RESULTS: Almost one-third of 7506 deliveries applied to immigrants; 36.3% of Greeks and 19.2% of immigrants [risk ratio (RR) = 0.53, 95% confidence interval (CI) = 0.52-0.54] delivered at ≥35 years; 10.5% of Greek and 7.0% of immigrant neonates weighted <2500 g (RR = 0.67, 95% CI = 0.61-0.74); 10.9% of Greeks and 8.1% of immigrants were born <37 wks (RR = 0.74, 95% CI = 0.67-0.82); 55.7% of Greeks and 48.2% of immigrants delivered by caesarean section (RR = 0.87, 95% CI = 0.85-0.88). CONCLUSION: We found that immigrant women deliver at a younger age, vaginally, more mature, and heavier neonates. Furthermore, we confirmed that the protective effect of immigrant status could not be explained by maternal age only.

Greek economic crisis and impaired perinatal parameters: experience from a public maternity hospital.

Since 2008, Greece suffers a severe economic crisis. Adverse health outcomes have been reported, but studies on perinatal health are sparse. We aimed to examine the impact of economic crisis on perinatal parameters during early and established crisis periods. Birth records of 14 923 neonates, born in a public maternity hospital from 2005-2014, were reviewed for maternal (age, delivery mode) and neonatal (gender, birthweight, gestational age) variables. Univariable analysis tested the association of study variables with time-periods 2005-2007, 2009-2011 and 2012-2014. Multivariable logistic regression analysis identified factors independently associated with low birthweight (LBW) (<2500 g), prematurity (<37 weeks) and caesarean section (CS). During 2012-2014, compared to 2005-2007, LBW rate increased from 8.4 to 10.5% (RR 1.16; 95%CI 1.01-1.33); prematurity from 9.7 to 11.2% (RR 1.09; 95%CI 0.96-1.24), comprising mainly late-preterm neonates; CS from 43.2 to 54.8% (RR 1.21; 95%CI 1.16-1.26). Maternal age ≥30 years was risk factor for LBW, prematurity and CS; LBW was additional risk factor for CS. However, LBW and CSs increased during the study period, independently of maternal age. In conclusion, impaired perinatal parameters, manifested by increasing maternal age, LBW, prematurity and CS rate, were observed during the years of economic decline, with possible adverse consequences for later health.

Maternal obesity and perinatal oxidative stress: the strength of the association.

Maternal obesity is a chronic inflammatory state, which has been shown to induce increased levels of free fatty acids, reactive oxygen species and inflammatory cells. Recent evidence reveals increased levels of lipid peroxidation products in the plasma of obese women during pregnancy. The aim of this study was to test the hypothesis that maternal overweight or obesity is associated with increased oxidative stress (OS) in offspring. Two hundred and forty-five pregnant women and their newborns were prospectively enrolled. Mothers were divided in two groups: lean control - LC (n=175, Group I); overweight or obese (n=70, Group II) according to BMI ≥ 25 before pregnancy. Cord blood F2-isoprostanes (F2-IsoPs), as reliable markers of OS, were measured in all newborns. Lower 1 minute APGAR score and higher weight at discharge were found in Group II neonates, compared to those of Group I (p less than 0.05). Small for gestational age (SGA) newborns of both groups showed increased levels of F2-IsoPs than appropriate (AGA) or large (LGA) for gestational age (GA) (p less than 0.01). SGA newborns of Group II had higher F2-IsoPs levels compared to SGA of Group I (p less than 0.01), which were significantly correlated to maternal BMI at the end of pregnancy (r=0.451, p less than 0.01). Multivariate regression analysis corrected for confounding factors, showed that maternal overweight or obesity was significantly associated with high F2-IsoPs levels in SGA offspring (p less than 0.01). Maternal overweight or obesity is associated with increased OS in their SGA newborns. Data suggest the need of antioxidant protection for both mothers during pregnancy and infants soon after birth.

Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort.

BACKGROUND: Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria. METHODS: Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge. RESULTS: Across Europe, 12 049 children were enrolled, and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA. CONCLUSIONS: This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon.

The implication of second-trimester amniotic fluid TNF-alpha, cytochrome C and cell death nucleosomes in the prediction of preterm labor and/or premature rupture of membranes.

AIM: The multifactorial pathway leading to preterm labor possibly includes the implication of apoptosis. This study aimed to clarify the role of amniotic fluid apoptotic molecules (TNF-alpha, cytochrome C and cell death nucleosomes) at midtrimester as possible predictors of preterm labor (PTL) and/or premature rupture of membranes (PROM). METHOD: In this case-control study, comprising 360 women undergoing genetic amniocentesis and out of whom 38 delivered preterm and 18 out of the latter after PROM, the above apoptotic molecules were determined by ELISA. The 38 cases with PTL and 18 cases with PROM were matched for age with 38 and 18 respective controls delivering at term, and the levels of apoptotic molecules were compared. RESULTS: Cell death nucleosome levels were found to be significantly associated with preterm delivery. Specifically, for every unit increase in nucleosomes, women were on average 0.2% more likely to deliver preterm (OR: 1.002, CI: 1.0-1.003, p = 0.018). In contrast, such an association was not found concerning the other two apoptotic molecules (TNF-a and Cytochrome C). CONCLUSION: Second-trimester amniotic fluid cell death nucleosomes' levels are significantly associated with preterm delivery and could possibly serve as predicting markers.

Caesarean section: impact on mother and child.

UNLABELLED: Maternal/foetal morbidity/mortality consequent to uterine rupture, placenta previa/increta and stillbirth may occur in repeat caesarean section (CS). Elective CS before 39 weeks increases respiratory complications, hypoglycaemia, sepsis and intensive care unit admissions. Different gut colonization in neonates born by CS accounts for increased incidence of food allergy, asthma and possibly type 1 diabetes. Epigenetic changes might be responsible - among others - for childhood malignancies. CONCLUSION: Decision for primary CS should take into consideration possible maternal/neonatal complications.

Simultaneous quantification of 17α-OH progesterone, 11-deoxycortisol, Δ4-androstenedione, cortisol and cortisone in newborn blood spots using liquid chromatography-tandem mass spectrometry.

Adrenal steroid profiling, including 17α-OH progesterone (17OHP), 11-deoxycortisol (S), Δ4-androstenedione (Δ4-A) and cortisol (F) in blood spots by tandem mass spectrometry, is used for newborn screening to detect congenital adrenal hyperplasia (CAH). Pre-analytical sample processing is critical for assay specificity and accuracy; however, it is laborious and time-consuming. This study describes the development and validation of a new Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method for the simultaneous quantification of five steroids: 17OHP, S, Δ4-A, F and cortisone (E) in blood spots from newborns. Whole blood was eluted from a 5.00 mm dried blood spot by an aqueous solution containing the deuterium-labeled internal standards d8-17OHP and d4-cortisol. The steroids extracted from blood spot into aqueous solution were subsequently purified via Extelut mini NT1 column using diethylether. The extracts were evaporated and quantified using LC-MS/MS. The detection limit was 0.25 ng/mL for 17OHP and S, 0.4 ng/mL for Δ4-A and 0.5 ng/mL for F and E. The limit of quantification was 0.5 ng/mL for 17OHP, S and Δ4-A and 1 ng/mL for F and E. Precision for 17OHP, S, Δ4-A at concentrations of 0.5, 2, and 8 ng/mL (n=5) in fortified steroid free serum samples was 1.3-3.5% (intra-assay CV) and 7-14.8% (inter-assay CV). Precision for F and E at concentrations of 5 and 20 ng/mL was 1.5-4.8% (intra-assay, CV%) and 6-15% (inter-assay, CV%). Accuracy was calculated at concentrations of 0.5, 2, and 8 ng/mL for 17OHP, S and Δ4-A and ranged from -0.3 to 0.2%, while for F and E it ranged from -3.2 to 0.2%. Relative recoveries at concentration 2 ng/mL and 8 ng/mL for 17OHP, S, Δ4-A and at 5 ng/mL and 20 ng/mL for F and E ranged from 55% to 80%. Reference intervals were estimated for all steroids in newborns (on day 3). The steroid profile assay herein described is sensitive, specific and accurate and involves a simple pre-analytical sample manipulation; it is therefore suitable for routine analysis and provides data for samples within normal range as well as those with elevated levels. For the first time to our knowledge, cortisone levels are reported in dried blood spots from newborns.

Mid-trimester amniotic fluid interleukins (IL-1ß, IL-10 and IL-18) as possible predictors of preterm delivery.

AIM: Strong evidence implicates chronic intraamniotic inflammation in the etiology of preterm delivery. The purpose of this study was to determine whether amniotic fluid IL-1ß, IL-10 and IL-18 concentrations in women undergoing mid-trimester amniocentesis can identify those at risk for preterm labor or preterm rupture of membranes. PATIENTS AND METHODS: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid IL-1ß, IL-10 and IL-18 in women delivering at term or preterm. Out of 362 women included in the study, 38 presented with preterm labor. Thirty-eight women with term delivery, matched for chronological and gestational age served as controls. Women with abnormal fetal karyotypes or major anomalies were excluded. IL-1ß, IL-10 and IL-18 concentrations were determined by ELISA. Conditional logistic regression was applied in the statistical analysis. RESULTS: IL-1ß was found to be positively and significantly associated with preterm delivery. Specifically, for every unit increase in IL-1ß, women were on average 7.2 (OR: 7.2, CI: 1.94-26.77, p=0.003) times more likely to deliver preterm. IL-18 levels as well as gender were significantly associated with preterm delivery. Specifically, for every unit increase in IL-18, women were on average 1% less likely to have a preterm delivery (OR: 0.99, CI: 0.98-0.99, p=0.04). On the other hand, IL-10 was not significantly associated with preterm delivery. CONCLUSION: Mid-trimester IL-1ß concentrations are positively associated with preterm delivery. Therefore, IL-1ß, determined on the occasion of mid-trimester amniocentesis could possibly serve as a marker of preterm delivery. In contrast, IL-10 and IL-18 concentrations are not elevated in mid-trimester amniotic fluid and probably cannot serve this purpose.

The role of human beta defensins 2 and 3 in the second trimester amniotic fluid in predicting preterm labor and premature rupture of membranes.

AIM: Human beta defensins 2 (HBD2) and 3 (HBD3) are peptides expressed in the amnion and chorion. This is a matched case control study conducted in our Department to determine whether second trimester amniotic fluid HBD2 and HBD3 concentrations measured at the time of genetic amniocentesis could be potential markers of preterm labor prediction. METHODS: Amniotic fluid HBD2 and HBD3 were determined by an enzyme-linked immunosorbent assay (ELISA) Women with preterm labor were defined as cases (N=41) while for each case a woman matched for age delivering at term served as control (N=41). Subgroup analysis was conducted to examine possible associations of HBD2 and HBD3 in cases of premature rupture of membranes. Nineteen women with preterm labor and premature rupture of membranes were defined as cases while for every case a woman matched for maternal age delivering at term served as control (N1=19). Results were presented as odds ratios (OR) and 95% confidence intervals. Statistical analysis used STATA 8.2 and SPSS 11.5 edition. A P-value of <0.05 was considered statistically significant. RESULTS: Amniotic fluid concentrations of HBD2 at the time of genetic amniocentesis were positively associated with preterm premature rupture of membranes (P=0.028), but not with preterm labour. No association of HBD3 and preterm birth was documented. CONCLUSION: Second trimester amniotic fluid HBD2 might be a predictor of premature rupture of membranes.

Adrenomedullin concentration in second trimester amniotic fluid cannot be used as a predictor of preterm delivery.

BACKGROUND: Adrenomedullin, secreted by decidua and trophoblast cells, is considered to participate in regulating uterine and placental blood flow, leading to control of placental hormonal secretion. Furthermore, adrenomedullin has an antimicrobial activity. The objective of this study was to determine whether adrenomedullin concentrations in midtrimester amniotic fluid can be used as a predictor of preterm delivery. PATIENTS AND METHODS: Amniotic fluid samples were collected in a retrospective cross-matched study that included 362 women with singleton pregnancies who presented for genetic amniocentesis. Adrenomedullin concentrations were determined by ELISA in amniotic fluid taken from women with spontaneous preterm delivery (n=41) and maternal age-matched controls who had normal pregnancy at term (n=41). RESULTS: No difference was found in adrenomedullin concentrations between women with spontaneous preterm delivery (median: 1.33 ng/ml, range: 0.36-8.53 ng/ml) and controls (median: 1.32 ng/ml, range: 0.33-4.07 ng/ml), nor between a subset of cases of preterm premature rupture of membranes (n=19) and their controls (n=19). CONCLUSION: Adrenomedullin concentration in amniotic fluid cannot serve as a predictor of preterm delivery.

Urocortin in second trimester amniotic fluid: its role as predictor of preterm labor.

BACKGROUND: The existence of a "placental clock" which determines the duration of gestation has been previously proposed. It is related to placental CRH secretion and is active from an early phase in human pregnancy. Urocortin is a specific ligand for the corticotropin-releasing factor (CRF) receptor expressed by human trophoblast and fetal membranes. The purpose of this study was to evaluate whether urocortin concentrations in the early second trimester amniotic fluid might serve to predict preterm delivery. METHOD: The urocortin concentrations in early second trimester amniotic fluid were measured in 41 pregnancies with term delivery and in 41 pregnancies with preterm delivery by using an immunoradiometric assay. Conditional logistic regression analysis was used for statistical analysis. RESULTS: Mean amniotic fluid urocortin concentrations in women with preterm labor were 1.55+/-0.63 ng/mL while those in women with term labor were 1.6+/-0.49 ng/mL (p: NS). No statistical significant results were found when comparing amniotic fluid urocortin concentrations in women with preterm premature rupture of membranes leading to preterm labor (n=19) to women with term delivery without premature rupture of membranes. CONCLUSION: These results suggest that urocortin concentrations in the amniotic fluid of genetic amniocentesis are not predictive of preterm labor and birth.

The role of urocortin in gynecological and obstetrical conditions.

AIM: The objective of the review is to present the possible role of urocortin, a novel peptide of the corticotrophin releasing factor family, in different conditions of obstetrics and gynecology such as preterm labor, preeclampsia or ovarian steroidogenesis. METHOD-RESULTS: A MEDLINE search was commenced with the terms "urocortin", "preterm labor", "preeclampsia", "ovary", "endometrium", "myometrium", "placenta", "plasma", "amniotic fluid". Seventy-three articles were found to be relevant on the field and the potential role of urocortin in such conditions is presented. CONCLUSION: Amounting data suggest that urocortin could play a significant role in human reproduction (steroidogenesis in the ovary, maintenance of the placental function and labor). Further investigation on the field is necessary in order to clarify the natural role of this newly identified molecule in the field of obstetrics and gynecology.

Intrauterine devices and extrauterine pregnancy. A literature review.

The incidence of ectopic pregnancy has been high over the last decades. Many risk factors are potential causes, among them IUDs use which might have a significant role. According to the current thinking, the use of IUD does not increase the risk of ectopic pregnancy. However, IUDs are more effective in protecting from intrauterine rather than ectopic pregnancy. Our review focuses on current and past IUD use, duration of its use, type of IUD and the associated risk of ectopic pregnancy. Fertility after IUD removal regarding the incidence of ectopic pregnancy is also discussed. Conflicting results regarding the association of ectopic pregnancy risk with the use of intrauterine devices exist.

Endothelin-3 and PRL levels in the maternal and fetal circulation at delivery.

OBJECTIVE: The aim of the present cross-sectional study was to test the hypothesis that endothelin-3 (ET-3) is involved in PRL secretion via systemic hormonal interaction during labor. MATERIALS AND METHODS: Fifty healthy pregnant women with singleton pregnancies were included in the present study. At delivery, blood samples were drawn from umbilical vein and artery. At the same time, a blood sample was obtained from a peripheral vein of the mother. In all blood samples, plasma ET-3 and serum PRL concentrations were determined. The main outcome measures were the differences between maternal peripheral blood, umbilical artery and vein in terms of ET-3 and PRL levels, and the associations between ET-3 and PRL levels. RESULTS: ET-3 values (mean+/-SEM) in umbilical artery did not differ significantly from those in umbilical vein (4.94+/-0.27 vs 5.05+/-0.32 pg/ml) but were in both vessels significantly higher than in maternal vein (1.14+/-0.56 pg/ml, p<0.001). Serum PRL values showed similar patterns. There was a significant positive correlation of the ET-3 levels between umbilical artery and vein (r=0.906, p<0.001), but not between maternal peripheral venous blood and the umbilical vessels. Similar correlations were found for PRL values. However, no significant correlations were found between ET-3 and PRL levels in all vessels studied. CONCLUSIONS: The present study demonstrates for the first time that ET-3 levels are higher in fetal than in maternal circulation at term. The lack of correlation between ET-3 and PRL levels suggests that ET-3 does not play an important endocrine role in the control of maternal and fetal PRL secretion during labor.

Adolescent pregnancy and perinatal outcome.

Adolescent pregnancy is associated with adverse maternal and fetal effects. Potential risk factors involve early dating behavior, early initiation of smoking, alcohol and substance abuse, low academic interest, single-parent families and, above all, poverty. Girls younger than 18 years and not legally majors are psychologically and socially underdeveloped, presenting higher obstetrical risks. Maternal complications due to adolescent pregnancy include, among others: anemia; pregnancy induced hypertension; sexually transmitted diseases; and premature labor and delivery. The most common complications concerning the infant are related to: low birth weight, due either to prematurity or intrauterine growth restriction; infection; chemical dependence (due to maternal substance abuse); sudden infant death syndrome; and increased morbidity and mortality during the 1st year of age. In addition, education of teenage mothers on the importance of pre-and postnatal care can reduce the poor perinatal outcome of both mother and infant.

Tissue polypeptide specific antigen and soluble Fas during normal pregnancy and early life.

BACKGROUND: Intrauterine fetal development is characterized by increased rates of proliferation and apoptosis, while both these processes may be attenuated post-natally. AIM: Tissue polypeptide specific antigen and sFas serum concentrations were determined during pregnancy and post-natally, in order to evaluate their alterations during these crucial periods. MATERIALS AND METHODS: Forty-seven healthy pregnant women, their full-term newborns and 35 healthy adults (controls) were included in the study. Markers were measured: (a) in maternal serum (MS), during the 1st, 2nd, 3rd trimester and at the 1st stage of labor; (b) in the umbilical cord (UC), during the 2nd stage of labor; (c) in neonatal serum in the 1st (IN) and 5th (5N) day after birth; and (d) in controls. RESULTS: The serum TPS concentrations in MS increased significantly with gestational age, being higher in the 3rd trimester and labor, than those in controls (p < 0.001). TPS values were significantly lower in the UC, compared to those in MS (p < 0.001), while they were markedly elevated in IN, compared to MS and UC (p < 0.001), and subsequently decreased in 5N (p < 0.001), remaining higher, than those in the controls (p < 0.001). Serum sFas concentrations in the MS depended significantly on gestational age (p < 0.001), being significantly lower in the first trimester, than those in the second (p < 0.003), the third (p < 0.03), in labor and controls (p < 0.005). sFas concentrations in the UC were significantly lower than in MS and controls (p < 0.001), while they increased significantly in 5N samples (p < 0.01). CONCLUSION: Our results demonstrate: (a) a higher apoptosis rate in the first trimester of pregnancy, possibly affecting maternal immuno-tolerance, followed by a down-regulation during the post-natal period; (b) a progressively increased proliferation from the first trimester to parturition, reflecting the fetal and placental growth and development, that seems to be thereafter moderated.

The varying patterns of neurotrophin changes in the perinatal period.

Neurotrophins (NTs), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 are of major importance in prenatal and postnatal brain development, due to their neuroprotective action. Developmental changes alter the neuronal responsiveness to certain NTs, which subsequently are variously expressed, to properly balance their action. The following study aimed at examining the pattern of perinatal changes of the four NTs--NGF, BDNF, NT-3, and NT-4 in 30 appropriate for gestational age (AGA) full-term fetuses and neonates by determining their circulating levels at characteristic time points. This study show a gradual decrease of circulating levels of the NTs, NT-3 and NT-4 from umbilical cord (UC) to neonates day 4 (N4), while circulating levels of NGF and BDNF present the opposite pattern: an increase from UC to N4. These patterns of perinatal changes differ according to their impact on the process of neuronal development and their reaction to perinatal stress. NT3 and NT4 have been documented to act at early stages of neuronal development and to decrease after hypoxia-ischemia, while NGF and BDNF to increase. Further studies should investigate these patterns in premature or full-term infants, presenting various pathological conditions in the perinatal period.

Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA Class II alleles as disease markers. A comparison between three European populations with variable rates of disease incidence.

BACKGROUND: To develop screening strategies for identification of individuals at increased genetic risk for type 1 diabetes in three populations with variable disease incidence rates and distinct ethnic origin. METHODS: A stepwise HLA DQB1-DQA1-DRB1-based screening approach was evaluated. Patients with childhood-onset type 1 diabetes were recruited from Finland (n = 1739), Hungary (n = 149), and Greece (n = 119). Consecutive newborns (2568 from Finland and 1047 from Greece) or healthy schoolchildren (n = 177 from Hungary) served as controls. RESULTS: The DQB1*02/0302 genotype conferred the highest disease risk in all populations. The DQB1*02/y (y not equal DQB1*0301,*0302,*0602,*0603, *0604) genotypes were more common and conferred a higher disease risk in the Greek population (OR 4.9) compared to the Finns (OR 1.2). DQB1*0302/x (x not equal DQB1*02, *0301, *0602, *0603, *0604) genotypes were, in contrast, more prevalent among Finnish cases (32.7%) as compared to Hungarians (18.1%) or Greeks (13.5%). The protective DQB1*0602 or *0603 positive genotypes were most common in the Finns, while DQB1*0301 was more common in Hungarians and Greeks. In all groups, DQA1 and DRB1*04 typing considerably increased the sensitivity of the DQB1-based screening. The different high-risk genotype combinations present in about 10% of the background population had a diagnostic sensitivity of 60% in Finland and 80% in Hungary and Greece. CONCLUSIONS: HLA DR-DQ-based screening is a feasible tool for the identification of individuals at increased genetic risk for type 1 diabetes in populations with diverse genetic background. The risk markers should, however, be individually selected for the target population since the screening efficiency of various markers is highly dependent on the ethnic group studied.

Alterations in Thl/Th2 cytokine concentrations in early neonatal life.

OBJECTIVE: To determine postnatal changes in neonatal serum concentrations of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and its soluble receptor (sIL-4R). METHODS: Forty-five healthy term neonates, 25 of the neonates' mothers and 27 healthy adults (controls) participated in the study. Cytokine concentrations were measured in blood samples from the umbilical cord, from the neonates on the 1st and 5th day after birth, from mothers and from controls. RESULTS: IFN-gamma concentrations were significantly lower in the umbilical cord, compared to concentrations in the controls (p < 0.04), and increased significantly from the umbilical cord to levels in neonates on day 5 (p < 0.03). In mothers and the umbilical cord, IFN-gamma concentrations were dependent on the mode of delivery, being higher after vaginal delivery than after elective Cesarean section (p < 0.005; p < 0.006, respectively). IL-4 concentrations in the umbilical cord for 1-day and 5-day neonates were significantly elevated compared to those in mothers (p < 0.001; p < 0.0007; p < 0.0001, respectively) and controls (p < 0.05; p < 0.01; p < 0.006, respectively). sIL-4R concentrations in all neonatal samples were significantly elevated compared to those in controls (p < 0.0001), the highest being found in 1-day-old neonates. A strong negative correlation was found between IL-4 and sIL-4R concentrations in 1- and 5-day-old neonates (r = -0.48, p < 0.002; r = -0.45, p < 0.0065, respectively). Moreover, IFN-gamma/IL-4 ratio increased significantly from the umbilical cord to 5 days of life (p < 0.03). CONCLUSIONS: Our findings indicate an earlier development of IL-4 than IFN-gamma, which could be viewed as a developmental characteristic in the ontogeny of the immune system.

Evidence for a suppression of apoptosis in early postnatal life.

BACKGROUND: In fetal life the rates of proliferation and apoptosis are high. We studied if the rate of apoptosis decreases after birth, by measuring the soluble (s) forms of Fas-Fas ligand and Tumor necrosis factor receptor 1 (TNFR1)-TNF-alpha which attenuate apoptosis. SUBJECTS AND METHODS: Blood was drawn from the umbilical cord and from a peripheral vein on day 1 and 4 of life in 35 infants and sFas, sFas ligand, sTNFR1 and sTNF-alpha were determined by enzyme immunoassays. Data were analyzed by paired t-test and Pearson's correlation analysis. RESULTS: sFas and sTNF increased significantly from birth to day 4 of life (p=0.033 and p<0.0001 respectively), while sTNFR1 increased significantly from birth to day 1 of life (p<0.0001) followed by a significant decrease on day 4 of life (p<0.0001). The levels of sFas and sTNF-alpha on day 1 correlated with those on day 4 (r=0.677, p<0.0002 and r=0.525, p<0.007 respectively). sFAS ligand was not detectable in any specimen. CONCLUSION: The increasing concentrations of the soluble molecules, sFas, sTNF-alpha and sTNFR1 might indicate that apoptosis may be downregulated in early postnatal life.