Serum soluble E- and L-selectin in the very early neonatal period.

Both E- and L-selectin are cell adhesion molecules. E-selectin is expressed by activated endothelial cells, whereas L-selectin by quiescent leukocytes and is rapidly cleaved off after activation. Both selectins take part in the first step of the 'adhesion cascade', the 'rolling of leukocytes', leading to the extravasation of the white cells to the sites of inflammation, infection or damage. For this reason their soluble forms (sE- and sL-selectin, respectively), are considered early and reliable markers of the immune activation and response. Moreover, sE-selectin has been reported to be a potent angiogenic factor and a reliable marker of infection and sepsis in neonates, as well as endothelial activation, while sL-selectin of the leukocyte function and maturity. Following informed maternal consent, we evaluated prospectively by ELISA, sE- and sL-selectin in the serum of 40 (19 females, 21 males), healthy, term, infection-free neonates, on the second and fifth day of life, and compared them with the respective values in 20 healthy adults (10 females, 10 males), with the purpose of examining the pattern of their values in the early postpartum days, and to establish reference values for both selectins. Values (mean+/-S.D.) of sE-selectin both on the second (139+/-48 ng/ml) and fifth day of life (111+/-35 ng/ml) were found to be highly increased, as compared with those in controls (48+/-13 ng/ml; P<4 x 10(-11) and P<4 x 10(-10), respectively), while sL-selectin values on both the second (674+/-223 ng/ml) and the fifth day of life (684+/-221 ng/ml), were significantly lower than those in controls (938+/-181 ng/ml); P<0.0001 and P<0.0003, respectively). A significant decrease was noted in sE-selectin values, from the second to the fifth day of life (P<10(-7)), while sL-selectin values showed no significant change in the same time interval. A strong correlation was found between values on the second and the fifth day of life of both sE- and sL-selectin (r(P)=0.885 and r(P)=0.813, respectively; P<0.00001). Neonatal values of both sE- and sL-selectin on the second or on the fifth day of life, did not depend on the perinatal factors, neonatal sex, or birth weight, mode of delivery, and maternal age or parity. In conclusion, in the very early neonatal period, our findings of highly increased sE-selectin, while low sL-selectin, suggest an immune and more specifically endothelial activation and an immature and decreased leukocyte function.

Serum leptin concentrations during the perinatal period.

We aimed to study maternal and infant serum leptin concentrations during the perinatal period and their relationship to the body weight of mothers and newborns. Serum leptin values were measured by enzyme-linked immunoadsorbent assay (ELISA) (R&D systems) in 26 healthy, term neonates during the first (N1) and fifth (N5) day after birth and were compared with serum leptin values in maternal blood (MS), amniotic fluid (AF), and umbilical cord (UC) at delivery. Twenty-five healthy, nonpregnant women, age and body weight-matched to the mothers, were used as controls (C). Infant serum leptin concentrations declined significantly after birth from UC to the N5 samples (p<0.003). MS leptin values were significantly higher than UC, N1, N5, and C values (p<0.001), while AF values were significantly lower than in controls (p<0.001). UC, but not MS leptin values correlated significantly with the birth weight of infants (r = 0.6; p<0.03). The elevated values of leptin in maternal serum and the regressing pattern of infant leptin values after birth suggest an additional, probably placental source of this protein during pregnancy, possibly contributing to the regulation of fetal body weight.

Soluble form of ICAM-1, VCAM-1, E- and L-selectin in human milk.

In breast milk and paired serum from 70 lactating women and 40 of their term, infection-free neonates, on the 2nd and 5th day postpartum slCAM-1, sVCAM-1, sE- and sL-selectin were measured by ELISA and compared with those in 26 healthy adults (controls). Seven infant formulas and fresh milk from five cows were also analyzed. Human colostrum values of slCAM-1, sVCAM-1 (similar to those in maternal and control serum), sE-selectin and sL-selectin (-10 and -100 times lower than in maternal and control serum) were significantly higher than those in milk, while they varied widely. None of the adhesion molecules was detected in fresh cow's milk or infant formulas. Exclusively breast-fed infants showed significantly higher values of slCAM-1 and sL-selectin on the 2nd day of life than those supplemented also with formula. Only slCAM-1 values correlated positively between colostrum and time-matched maternal serum. These findings show in human milk important amounts of slCAM-1 and sVCAM-1 but minimal amounts of sE- and sL-selectin, which could affect the immune system of the neonate.

Patterns of inflammatory cytokine serum concentrations during the perinatal period.

Inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured in the serum of healthy, term neonates on the first (N1), fifth (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and in adult controls. All three cytokines were significantly elevated in N1 and N5, compared with those in UC and adults (P < 0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P < 0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. TNF-alpha values in UC were significantly higher than in adults, but lower than in N40 (P < 0.0001), while IL-1beta and IL-6 values in UC did not differ from those in N40 and in adults. IL-1beta and IL-6, but not TNF-alpha values in MS were significantly higher than those in controls (P < 0.0001). IL-1beta values in MS were significantly higher than those in N1 (P < 0.0001), while those of IL-6 and TNF-alpha were significantly lower (P < 0.0001). Moreover, IL- 1beta values were dependent on the mode of delivery in N1 (P < 0.001), in MS (P < 0.02) and in UC (0.03), while IL-1beta and TNF-alpha values in N1 were strongly interrelated (r = 0.7; P < 0.01). In conclusion, the increased values of IL-1beta, IL-6 and TNF-alpha during the perinatal period might reflect a newborn immune response to the stress of delivery and to environmental changes after birth.

Soluble intercellular adhesion molecule-1 in newborn infants.

UNLABELLED: The aim of this study was to evaluate the effect of increasing postnatal age on soluble intercellular adhesion molecule-1 (sICAM-1), a very early and sensitive marker of immune activation and response in the serum of newborn infants. Serum sICAM-1 was measured by EIA (T Cell Diagnostics) in 20 healthy adults (controls) and in 43 (24 females/19 males) healthy neonates, of whom 28 were full term, and 15 were born at a gestational age between 35 and 38 weeks of pregnancy, on the 1st, 5th and 30th day of life. Neonatal serum sICAM-1 values showed a very significant increase (P < 0.01) from the 1st day (137.3+/-62.0 ng/ml) to the 5th day (259.3+/-124.0 ng/ml) and then to the 30th day of life (415.0+/-114.0 ng/ml), being significantly lower on the 1st day (P < 0.01), whereas significantly higher on the 30th day of life (P < 0.05), than those in healthy adults (305+/-195 ng/ml). Serum sICAM-1 values on the 1st day of life depended on both the mode of delivery (significantly higher in neonates born vaginally) and the gestational age at birth (significantly lower in those born at a gestational age over 38 weeks). A significant strong correlation was found in sICAM-1 values between the 1st and the 5th day following delivery (rp = 0.77, P < 0.009). CONCLUSION: The results of this study demonstrate a significant rise of serum sICAM-1 during the 1st month of life in healthy neonates suggesting a progressively increased activation of the neonatal immune system.

Inflammatory cytokines in newborn infants.

Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

Changes of angiogenin serum concentrations in the perinatal period.

The polypeptide angiogenin, a normal constituent of human plasma, might be involved in endothelium homeostasis, angiogenesis, and neovascularization accompanying various diseases. This study aimed at determining angiogenin serum concentrations in the perinatal period of healthy newborns and at forming a baseline for this protein, which in the future may serve as a diagnostic index in developmental errors of the placenta and/or newborn. One milliliter of blood was drawn on d 1 and 4 of life from 30 healthy full-term neonates, and angiogenin serum concentrations were measured by an enzyme immunoassay using a commercially available kit. In 10 cases angiogenin serum concentrations were also measured in the maternal serum before delivery and in the umbilical vein serum. Angiogenin serum concentrations (microgram/L) were significantly higher in maternal serum (225.7 +/- 49.6) compared with umbilical vein serum (119.0 +/- 34.2) (p < 0.0002), as well as that compared with day 1 (166.4 +/- 44.9) (p < 0.01) but not to d 4 neonatal serum (240.8 +/- 52.6). Angiogenin serum concentrations showed a statistically significant increase from d 1 to 4 (p < 10(-7)), as well as from umbilical cord serum to d 1 neonatal serum (p < 0.0002). A statistically significant correlation existed between values in umbilical cord serum and d 1 neonatal serum (r = 0.84, n = 10, p < 0.002) and between those in d 1 and 4 neonatal serum (r = 0.37, n = 30, p < 0.04). Sex, birth weight, or mode of delivery did not influence angiogenin serum concentrations. We conclude that a rapid increase of angiogenin serum concentrations to maternal levels takes place during the first four postnatal days in healthy full-term neonates.

Non-stress test: a fifteen-year clinical appraisal.

During a 15-year period (Jan. 1981 to Dec. 1995) a total of 14,950 patients were delivered in our hospital. Throughout this period fetal heart rate monitoring during labor was increased from 10% up to 85%. The overall antepartum testing was also increased from 8 to 15%. In patients with significant complications in pregnancy the mean number of non-stress tests (NST's) per patient was 1.8 tests in 1981 to 4.8 tests in 1995. The average perinatal mortality was 15.2/1000, with a gradual decline. In patients who were subjected to antepartum testing the previous rate was only 3.7%/1000. Our conclusion is that the use of antepartum and intrapartum cardiotocography has increased during the last 15 years in our clinic. As a consequence a considerable decrease was noted in the overall perinatal mortality. The non-stress test is still today the first line of antepartum fetal assessment.

Cystic hygromas associated with Turner's syndrome. Report of three cases.

Three cases of cystic hygromas are reported. Two of these were singleton pregnancies diagnosed at 20 weeks' gestation and the other was an affected fetus in a twin pregnancy at 19 weeks gestation. Amniocentesis was done and chromosomal analysis revealed Turner syndrome in all cases. The two singleton pregnancies were terminated by intrauterine installation of PgF2a. The affected fetus of the twin pregnancy died at 24 weeks' gestation and the pregnancy continued.