Estimation of fetal oxygen uptake in human term pregnancies.

OBJECTIVE: Umbilical oxygen (O(2)) uptake is a parameter of basic physiologic interest. It has been extensively studied in chronically catheterized animals but very few data have been obtained acutely in humans. Recent developments in ultrasound technology allow the estimation of umbilical venous blood flow in utero. METHODS: In all, 26 normal term pregnancies were studied at the time of elective cesarean section in order to evaluate fetal O(2) uptake as the product of umbilical blood flow and umbilical O(2) veno-arterial difference. An ultrasound evaluation was performed within 1 h from delivery: umbilical vein area and flow velocity were recorded to calculate umbilical vein volume flow (Q(umb)). Blood samples from the umbilical vein (uv) and artery (ua) were obtained at the time of fetal extraction for respiratory gases and acid-base evaluation. RESULTS: Umbilical O(2) uptake was calculated as Q(umb) • (uv-ua)O(2) content: an average value of 0.84 ± 0.40 mmol/min was obtained. Umbilical O(2) uptake per kg was 0.25 ± 0.12 mmol/kg/min, significantly related to fetal O(2) delivery. CONCLUSIONS: We estimated umbilical blood flow by ultrasound and we measured umbilical O(2) uptake at term obtaining a value of umbilical O(2) uptake/kg similar to what previously reported in human pregnancies and chronically catheterized animals.

First trimester PTX3 levels in women who subsequently develop preeclampsia and fetal growth restriction.

Pentraxin 3 (PTX3) and C-reactive protein (CRP) levels were measured in the first trimester of pregnancy in women who subsequently developed preeclampsia (PE, n=16) and fetal growth restriction (FGR, n=12) requiring iatrogenic delivery before 37 weeks, and those who had uncomplicated pregnancies delivering at term (n=60). Mean PTX3 levels were significantly higher in women who subsequently developed PE (7.31 ng/ml, SD = 4.12) when compared to those with normal pregnancy outcome (4.92 ng/ml, SD = 1.94, p=0.0046). There were no significant differences between PTX3 levels in women with FGR (4.82 ng/ml, SD = 2.35) compared to normal pregnancy outcome (p=0.88). The median CRP levels did not vary significantly between the three groups (p=0.26). PTX3 levels in women who subsequently develop PE are already elevated in the first trimester, but not in those that develop FGR. This supports the hypothesis of an excessive maternal inflammatory response to pregnancy in the etiology of PE.

Maternal and fetal fatty acid profile in normal and intrauterine growth restriction pregnancies with and without preeclampsia.

The aim of this study was to evaluate maternal and fetal lipid profile in intrauterine growth restriction (IUGR) pregnancies with and without preeclampsia (PE). Thirteen normal pregnancies studied during the third trimester (control M) and 29 at elective cesarean section (control CS) were compared with 18 pregnancies complicated by IUGR (IUGR only) and with seven pregnancies complicated by both IUGR and PE (IUGR-PE). Total plasma fatty acids, triglycerides, cholesterol, and nonesterified fatty acids (NEFA) were determined in maternal and fetal plasma. Nutritional intake was analyzed. IUGR only mothers had lower percentage of linoleic acid (LA) and higher arachidonic acid (AA) than controls, partly explained by higher AA dietary intake. Higher levels of NEFA were observed both in IUGR only and in IUGR-PE mothers whereas triglyceride levels were increased in IUGR-PE mothers only. In IUGR-PE fetuses, LA and AA were significantly decreased, whereas triglyceride and NEFA concentrations were significantly increased compared with normal fetuses. In conclusion, IUGR only is associated with altered fatty acids profile not completely accounted by dietary changes. We hypothesize that the differences observed in IUGR with PE for triglycerides and other lipids could be related to a difference in maternal phenotype.

Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies.

OBJECTIVE: The aim of this study was to evaluate how resistin and adiponectin (ApN) are involved in maternal energy metabolism and foetal growth. DESIGN: A cross-sectional study. PATIENTS AND MEASUREMENTS: Resistin and ApN were measured in 30 healthy nonpregnant women, 73 pregnant women [10-41 weeks of gestation; 18 with gestational diabetes mellitus (GDM), five with pregnancy-induce hypertension (PIH), nine with pre-eclampsia (PE), eight with chronic hypertension (CH) and 33 normal] and 40 foetal samples (20-41 weeks of gestation; 18 from GDM mothers and 22 from normal mothers). RESULTS: Resistin levels were significantly higher in normal pregnant women than in nonpregnant controls (13.7 +/- 2.1 vs. 6.3 +/- 1.6 ng/ml; P < 0.005) and showed a negative correlation with gestational age (P < 0.0001, r = -0.7). Only women with PE presented resistin levels significantly lower than normotensive women of the same gestational age (8.2 +/- 1.2 vs. 17.9 +/- 4.3 ng/ml; P < 0.005). ApN levels, although similar in normal pregnant women to those in nonpregnant controls, were significantly lower in women with GDM (37-41 weeks; 5.2 +/- 0.5 vs. 8.2 +/- 0.8 mg/l; P < 0.0001) and PE (20-37 weeks; 5.0 +/- 0.7 vs. 9.5 +/- 0.7 mg/l; P = 0.008) than those found in normal women matched for gestational age. Resistin was detected in the umbilical venous blood in foetuses from 20 to 41 weeks of gestation. In all newborns, both resistin and ApN levels were significantly higher than those recorded in adult life and did not correlate with maternal levels (P = ns, r = 0.03 for resistin and P = ns, r = -0.3 for ApN). Foetuses from diabetic mothers had ApN significantly lower than normal foetuses (26.8 +/- 2.6 vs. 37.5 +/- 3.5 mg/l; P = 0.02), while resistin levels were similar (17.3 +/- 3.7 vs. 18.2 +/- 1.5 ng/ml; P = ns). CONCLUSION: The secretion pattern of ApN in normal and complicated pregnancies strongly suggests an involvement of ApN in insulin resistance during gestation, while resistin seems to have a minor role. Moreover, the detection of high levels of resistin and ApN in cord blood during gestation is consistent with a regulatory action of these adipokines on tissue differentiation and foetal growth.

Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition.

Among other factors, fetal growth requires maternal supply of cholesterol. Cellular cholesterol uptake is mainly mediated by the LDL receptor (LDL-R) and the scavenger receptor family. We hypothesized that expression levels of key receptors of these families were regulated differently in placentas from IUGR pregnancies with varying degrees of severity. Third-trimester placentas from IUGR pregnancies with (IUGR-S) and without (IUGR-M) fetal hemodynamic changes and from control (AGA) pregnancies were studied. LDL-R, LDL-R-related protein (LRP-1), and scavenger receptor class B type I (SR-BI) mRNA and protein levels were measured. Cholesterol concentration and composition of lipoproteins were analyzed enzymatically and by lipid electrophoresis, respectively, in maternal and umbilical cord blood. LDL-R mRNA levels in IUGR-M were similar to AGA but lower (P < 0.05) in IUGR-S. In contrast, LDL-R protein was twofold (IUGR-M) and 1.8-fold (IUGR-S) higher (P < 0.05) than in the AGA group. LRP-1 mRNA and protein levels were not altered in the IUGR cases. SR-BI mRNA was unchanged in IUGR, but protein levels were lower (P < 0.05) in IUGR-S than in the other groups. Maternal plasma concentrations of LDL cholesterol were higher (P < 0.05) in the AGA group (188.5 +/- 23.6 mg/dl) than in the IUGR-S group (154.2 +/- 26.1). Electrophoretic mobility of the LDL fraction in maternal plasma demonstrated significant changes in migration toward higher values (AGA 0.95 +/- 0.06, IUGR-M 1.12 +/- 0.11, P < 0.001; IUGR-S 1.28 +/- 0.20, P = 0.002). We conclude that LDL-R and SR-BI levels are altered in IUGR pregnancies. These differences were associated with changes in LDL, but not HDL, mobility and cholesterol concentration in maternal circulation.

Elevated maternal levels of the long pentraxin 3 (PTX3) in preeclampsia and intrauterine growth restriction.

OBJECTIVE: The prototypic long pentraxin pentraxin 3 is a new candidate marker for inflammatory conditions reflecting the involvement of the vascular bed. Endothelial dysfunction is a prominent feature of preeclampsia as a result of excessive maternal systemic inflammation. We investigated pentraxin 3 levels in preeclampsia and intrauterine growth restriction, pregnancy conditions related to altered placentation. STUDY DESIGN: We cross-sectionally studied nonpregnant women (n = 20); normal pregnancies in the first (n = 8), second (n = 10), and third (n = 26) trimester of pregnancy; 20 pregnancies complicated by preeclampsia; and 16 pregnancies complicated by intrauterine growth restriction. Maternal plasma samples were analyzed and pentraxin 3 determined by enzyme-linked immunosorbent assay. Pattern and site of placental expression of pentraxin 3 were studied by immunohistochemistry. RESULTS: In normal pregnancies pentraxin 3 concentrations were significantly higher than nonpregnant women and did not change among the 3 trimesters. Significantly higher levels of pentraxin 3 were found in preeclampsia (median values 13.8 versus 2.2 ng/mL; P < .001), compared with normal pregnancies. Intrauterine growth restriction pregnancies showed intermediate levels between normal and preeclamptic patients, but this difference was not significant, compared with normal pregnancies (median values 3.9 versus 2.2 ng/mL). No significant difference of pentraxin 3 levels was found between mild and severe preeclampsia. CONCLUSION: Elevated maternal plasma levels of pentraxin 3 in preeclamptic versus normal pregnancies could represent a marker of altered endothelial function, typical of preeclampsia.