Non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in families from a Greek island with a closed society.

In young members of a large family from a Greek island with a closed society, clinical and hormonal symptoms of 21-OH deficiency (CAH) were present. To discriminate those affected from those unaffected, we measured the basal and ACTH stimulated 30 values of 17-hydroxyprogesterone (17-0HP) progesterone (P) and cortisol (F) in combination with HLA-phenotypes in 25 out of 40 members of this family. The indices of the Gutai30-min assessment (17-0HP+P response to ACTH testing at 30 min), GF (F response at 30 min) and the ratio GF30/Guai30 named the Marina index were evaluated. The Marina index showed a very statistically significant difference among the three groups (p < 0.001). HLA phenotypes of the members of groups A and B showed a powerful association with B14, DR1, B7, and B35 phenotypes that were related with 21-OH/CAH. In conclusion, in our study population, a high incidence of a clinically asymptomatic form of 21-OHdef was found only after the ACTH stimulation test. The Marina index seems to be of high diagnostic value in classifying disease severity.

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.

Effect of hormone therapy, tibolone and raloxifene on circulating vascular endothelial growth factor in Greek postmenopausal women.

OBJECTIVE: To evaluate the effect of continuous combined hormone therapy (HT), tibolone and raloxifene on circulating vascular endothelial growth factor (VEGF) in postmenopausal women. DESIGN: One-year prospective intervention study. METHODS: One hundred and forty-six postmenopausal women with a mean age of 51.8+/-4.1 (s.d.) years received 0.625 mg conjugated equine estrogen (CEE) plus 5 mg medroxyprogesterone acetate (MPA) (CEE/MPA, n=34), 2.5 mg tibolone (n=37), 60 mg raloxifene (n=40) or no active treatment (control group, n=35). Plasma VEGF was estimated at baseline and at 6 and 12 months. RESULTS: In both the CEE/MPA-treated and the tibolone-treated groups plasma VEGF increased significantly at month 6 and remained elevated at month 12 (CEE/MPA baseline: 268.1+/-187.8 pg/ml, month 6: 320.0+/-175.3 pg/ml, month 12: 321.1+/-181.8 pg/ml, P=0.01; tibolone baseline: 240.6+/-165.8 pg/ml, month 6: 271.4+/-172.7 pg/ml, month 12: 274.8+/-183.1 pg/ml, P=0.03). These changes were significantly different from the respective changes in the control group after adjusting for T-score in bone densitometry (CEE/MPA: P=0.02, tibolone: P=0.04). The effect of HT or tibolone on plasma VEGF was mainly evident in women with low baseline VEGF levels (<243.2 pg/ml, median for whole sample). On the contrary, VEGF levels in the raloxifene-treated or the control group did not change throughout the study. CONCLUSION: Both continuous combined HT and tibolone increased circulating VEGF in postmenopausal women, while raloxifene had no effect. Further research is needed to clarify the clinical relevance of these findings with respect to cardiovascular risk in postmenopausal women.

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.

Concentrations of angiogenic factors in follicular fluid and oocyte-cumulus complex culture medium from women undergoing in vitro fertilization: association with oocyte maturity and fertilization.

OBJECTIVE: To determine the concentration of angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and angiogenin) in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte. DESIGN: Prospective study. SETTING: Academic tertiary-care institution. PATIENT(S): IVF patients with unexplained or tubal factor infertility. INTERVENTION(S): Analysis of VEGF, bFGF, and angiogenin FF and CM concentrations. MAIN OUTCOME MEASURE(S): Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations. RESULT(S): VEGF, bFGF, and angiogenin were determined in FF and CM. FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature. CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized. Positive correlations were observed between angiogenic factors in CM. CONCLUSION(S): VEGF, bFGF, and angiogenin (determined for the first time) are secreted in the FF and CM. Elevated CM VEGF concentrations, probably implying oocyte-cumulus complex hypoxia, are negatively associated with oocyte fertilization. Elevated FF angiogenin concentrations are positively associated with oocyte maturity, possibly indicating angiogenin's biological role beyond neovascularization.

Mucin-like carcinoma-associated antigen (MCA) during normal pregnancy.

OBJECTIVE: To assess the usefulness of Mucin-like carcinoma-associated antigen (MCA) in monitoring pregnant patients with breast cancer. STUDY DESIGN: Maternal serum (MS) and amniotic fluid (AF) antigen values were measured by an enzyme immunoassay in 30 pregnant women during the second trimester, in 28 during the third and in 26 at parturition. Sera only from 26 women in the first trimester and from 26 healthy, non-pregnant women (controls) were also analyzed. RESULTS: Maternal serum MCA concentrations increased significantly with gestational age (p<0.0001). The frequency of elevated serum values was 5% in the first, 35% in the second and 100% in the third trimester and at parturition. Antigen values in AF were markedly higher than those in MS (p<0.0001) and increased also significantly with advancing gestation (p<0.0001). A strong correlation was observed between MS and AF antigen values (r=0.77, p<0.0001). Maternal serum values at parturition were dependent on the mode of delivery, being higher in the cases who delivered vaginally, compared to those delivered by elective caesarean section (p<0.006). CONCLUSION: Our data suggest that pregnancy affects significantly maternal serum MCA. Consequently, MCA seems to be a non-reliable marker in monitoring pregnant patients.

Hypothalamic-pituitary-thyroidal axis dysfunction and cortisol secretion in patients with nonclassical congenital adrenal hyperplasia.

OBJECTIVE: The purpose of this study was to evaluate thyroid function and TSH and cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when compared with women with hyperandrogenemic symptoms (menstrual irregularities, hirsutism, acne, seborrhea and sterility) of other etiologies (Group B). METHODS: Seventy-two women were subjected to stimulation of the adrenal cortex with i.v. ACTH administration in the early proliferative phase of the menstrual cycle. Basal plasma TSH, T3, T4, and FTI as well as basal and ACTH-stimulated plasma F and 17-hydroxyprogesterone levels were determined. RESULTS: According to internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH patients as well as affected heterozygotes of the disease. No significant difference was found in the plasma T3, T4, or FTI or F concentrations between the women of the two groups. On the contrary, plasma TSH levels were significantly lower in patients with 21-hydroxylase deficiency when compared to the women with hyperandrogenemic symptoms of other etiologies. CONCLUSION: The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns.

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.

Changes in serum levels of vascular endothelial growth factor in males and females throughout life.

OBJECTIVES: To study serum levels of vascular endothelial growth factor (VEGF), a potent angiogenic factor, during distinct periods of the female life span and compare them with corresponding levels of age-matched males. It is hypothesized that VEGF might be increased at periods of enhanced angiogenesis. METHODS: Venous blood was drawn from healthy females (n = 59) and males (n = 53) divided into six groups: fetuses (cord blood), neonates, children, adults (same females in the proliferative and secretory phases of their menstrual cycle), pregnant, and elderly (postmenopausal). Serum VEGF levels were measured by an enzyme immunoassay. RESULTS: Females showed 49% higher serum VEGF levels than males (t = 2.74, P = .01). Cord and neonatal blood levels were significantly increased compared with those of adults (t = 2.41, P = .02, and t = 5.81, P = .0001, respectively). All female age groups presented higher serum VEGF levels than the group of women in the proliferative phase of the cycle; nevertheless, VEGF levels in the secretory phase did not differ (t = 1.85, P = .07). CONCLUSIONS: Serum VEGF levels are higher in females than in males and during life periods characterized by enhanced growth and development, implying increased rates of angiogenesis.

Tissue polypeptide specific antigen (TPS) throughout normal pregnancy.

AIM: TPS concentrations were measured throughout normal pregnancy in maternal serum (MS) and amniotic fluid (AF), in order to evaluate the usefulness of TPS in the follow-up of pregnancy breast cancer patients. PATIENTS AND METHODS: Following informed consent, 30 pregnant women during the 2nd trimester, 28 during the 3rd and 26 at parturition were included in the study. For comparison, 28 women in the 1st trimester and 28 healthy, non pregnant women (controls) were also studied. Both MS and AF antigen values were measured by an enzyme immunoassay (BEKI Diagnostics). RESULTS: Maternal serum TPS concentrations increased significantly with gestational age (p < 0.0001), being significantly higher in the 3rd trimester and during labor than those in the controls (p < 0.0001). Amniotic fluid TPS values were markedly elevated, compared with those in MS (p < 0.0001, paired-t-test), declining significantly from the 2nd to the 3rd trimester (p < 0.0015) and labor. Both MS and AF TPS values during labor depended on the mode of delivery, being higher in the cases terminated by vaginal delivery, compared to those by elective cesarean section. CONCLUSION: Maternal serum TPS values are influenced significantly by pregnancy, and thus, this antigen, as tumor marker seems to be reliable only during early pregnancy.

Angiogenic factors in the perinatal period: diversity in biological functions reflected in their serum concentrations soon after birth.

These studies investigated whether serum levels of the angiogenic factors angiogenin, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) change soon after birth due to the elimination of the placenta and to diminished angiogenic but increased adaptational demands in extrauterine life. Also investigated was whether serum levels correlate with sex, birth weight, or mode of delivery. Serum from healthy mothers and their healthy full-term infants at birth (umbilical cord, UC), day 1 (N1) and day 4 (N4) postpartum was analyzed by enzyme immunoassays. Angiogenin levels were higher in maternal serum and rose significantly from UC to N1 and N4, possibly because of the elimination of the placenta, which produces an angiogenin inhibitor. bFGF and VEGF maternal levels were lower than fetal and neonatal ones. Although neonatal bFGF levels did not differ from fetal levels, possibly reflecting diminished angiogenesis ex utero, VEGF levels increased in neonatal serum, possibly signifying adaptational demands. Neither factor depended on sex, mode of delivery, or birth weight. Thus, significant differences from normal reference values of the studied factors might reflect ill-defined situations of the placenta and fetus/newborn serving as early diagnostic markers.

A comparative study of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 in preeclampsia.

OBJECTIVES: Maternal serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in preeclampsia to investigate whether these molecules could be helpful with regard to this pregnancy complication. STUDY DESIGN: The study population was composed of 30 preeclamptic patients with a mean gestational age of 35.5 +/- 4.6 weeks and 20 age-matched and gestational age-matched normotensive uncomplicated pregnancies (controls). Blood samples from 7 of the 30 preeclamptic patients and 15 of the 20 controls in the second trimester were also analyzed. Data were analyzed by parametric methods. RESULTS: Significantly higher maternal serum sVCAM-1 levels were found in both groups of preeclamptic patients with and without fetal growth restriction (981 +/- 145 ng/ml; n = 13; p < 0.0005 and 846 +/- 84 ng/ml; p < 0.02, respectively) compared with controls (668 +/- 186 ng/ml). In contrast, no significant difference was found in maternal serum sICAM-1 levels between preeclamptic and normotensive pregnancies, or in both adhesion molecules (1) in the controls between second and third trimester samples and (2) in the second trimester between pregnant women who developed preeclampsia later and gestational age-matched controls. CONCLUSION: These findings show a selective significant elevation of maternal serum sVCAM-1 in preeclampsia, with the highest values in cases complicated with fetal growth restriction, perhaps reflecting its angiogenic function. Hence, sVCAM-1 could be helpful in the diagnosis of this fetal complication in preeclampsia.

Basic fibroblast growth factor: serum levels in the female.

This study investigated serum levels of basic fibroblast growth factor (b FGF), a potent angiogenic factor, during distinct periods of the female life and compared them with corresponding levels in age-matched males. Healthy females (n = 59) and males (n = 53) were included in the study, divided into six groups: fetuses (cord blood), neonates, children, adults (females in proliferative and secretory phase), pregnant and "elderly" men and women. Serum b FGF levels were measured by an enzyme immunoassay. No statistically significant difference was found between both genders. Blood levels in fetuses and neonates were significantly increased as compared to adults (p = 0.01, p = 0.02, respectively). Restricting the analysis to females, all age groups, but fetuses (p = 0.05), demonstrated no difference when compared to proliferative phase adults. In conclusion, b FGF serum levels do not differ between males and females and are elevated in fetal and neonatal life, when growth and development are enhanced.

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.

Serum angiogenin levels in the female from birth to postmenopause.

This study investigated serum angiogenin levels of the potent angiogenic factor angiogenin, during fetal and neonatal life, childhood, adulthood, pregnancy and postmenopause and compared them with respective levels in age-matched males. Serum angiogenin levels were measured by an enzyme immunoassay in 139 healthy male and female subjects, allocated in the above six groups. Multiple linear regression applied (a) for both genders and (b) only for females showed serum angiogenin levels in adults to differ statistically highly significantly from levels in cord blood (P = 0.0001), neonates (P = 0.0001), children (P = 0.0001), and pregnant women (P = 0.01), but not from "elderly" subjects (P = 0.80). A significant difference existed between levels in the proliferative and secretory phase of the menstrual cycle (P = 0.006). Furthermore, a significant trend for serum angiogenin levels with advancing age groups was noted (P = 0.0001). In conclusion, serum angiogenin levels increase significantly from fetal life to adulthood, possibly implying additional biological functions to that of angiogenesis.

Heparin-binding angiogenic factors (basic fibroblast growth factor and vascular endothelial growth factor) in early neonatal life.

This study investigated whether serum levels of the potent angiogenic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), which are abundantly produced in utero by the placenta and fetal tissues, change after birth at term, consequent to diminished angiogenic but increased adaptational demands in extrauterine life. Moreover, whether serum levels of the above factors correlate with sex, birth weight, or mode of delivery was also evaluated. One milliliter of blood was drawn from 30 healthy, appropriate for gestational age, full-term infants on d 1 (N1) and 4 (N4) postnatally. In 10 of the above cases maternal and umbilical cord blood samples were also drawn. Serum was analyzed by enzyme immunoassays, using commercial kits. Levels of bFGF and VEGF were significantly lower in maternal serum than in umbilical cord (p = 0.02 and 0.036, respectively) or N1 (p = 0.009 and 0.006, respectively) and N4 serum (p = 0.009 and 0.006, respectively). Levels of bFGF in umbilical cord serum did not differ significantly from those in N1 and N4. In contrast, levels of VEGF rose in N1, differing significantly from levels in umbilical cord serum (p = 0.008). Both factors did not change from N1 to N4. Neither bFGF nor VEGF serum levels depended on sex, mode of delivery, or birth weight. In conclusion, bFGF levels in neonates do not differ from levels in fetuses, possibly reflecting diminished angiogenesis in extrauterine life, which already has started in utero. On the contrary, neonatal levels of VEGF rise significantly after birth, possibly signifying adaptation demands, in addition to angiogenesis, as VEGF is also considered a regulator of normal function.

Breast cancer markers during normal pregnancy.

AIM: To measure MCA and CA153 concentrations in maternal serum (MS) and amniotic fluid (AF) paired samples during normal pregnancy, in order to evaluate the usefulness of these markers in monitoring pregnant patients with a history of breast cancer. PATIENTS AND METHODS: Serum and AF MCA and CA153 values were measured in 20 pregnant women during the 1st trimester, 29 cases in the 2nd, 26 in the 3rd and 20 at parturition and compared with those of 20 healthy, age-matched, non pregnant women (controls). RESULTS: MS values of MCA increased significantly with gestational age (p < 0.0001), being higher in the 3rd trimester and in labor than in control values (p < 0.0001). MCA values in AF were remarkably higher than those in MS and increased significantly with advancing gestation (p < 0.0001). In contrast, CA153 values in AF, which were marginally higher than in MS, did not differ significantly with the progression of pregnancy. CONCLUSIONS: Maternal serum MCA values are significantly influenced during pregnancy. Thus, this marker seems to be reliable only during early pregnancy. In contrast, CA153 remains a useful marker in monitoring pregnant breast cancer patients.