Second Trimester Of Normal Pregnancy Research Articles

Human Miscarriage Is Associated With Dysregulations in Peripheral Blood-Derived Myeloid Dendritic Cell Subsets.

Dendritic cells (DC) are critically involved in decisions related to the acceptance or rejection of the foreign fetal antigens by the maternal immune system. However, particularly for human peripheral blood DCs (PBDC), available literature is rather inconsistent and the factors regulating these cells are ill-defined. Here, we investigated the phenotype and functionality of different human PBDC subsets during normal and pathologic pregnancies and studied an involvement of human chorionic gonadotropin (hCG) in PBDC regulation. Peripheral blood samples were obtained from normal pregnant women in all three trimesters, from first trimester miscarriage patients and from healthy non-pregnant women. Samples were analyzed for plasma hCG levels, for regulatory T (Treg) cell numbers, for frequencies of total and mature plasmacytoid (PDC) and myeloid (MDC1 and MDC2) PBDC subsets and for their cytokine secretion. In vitro assays, culturing PDC, MDC1 or MDC2 in the presence of two trophoblast cell lines, placenta explant supernatants or two hCG preparations were performed. The Treg-inducing capability of hCG- or non-hCG-treated stimulated MDC1 was assessed. Total and mature MDC1 and MDC2 frequencies increased during the first and second trimester of normal pregnancy, respectively. Miscarriage was associated with a reduced MDC1 and an increased MDC2 activation profile. PDC were not altered neither during normal pregnancy progression nor during miscarriage. In vitro, the culture of isolated PBDC subsets in the presence of placenta-derived factors impaired the maturation of MDC1 and differentially affected PDC maturation. An inhibitory effect on MDC1 and PDC maturation was also proven for the urine-derived hCG preparation. Finally, we observed a Treg cell elevation during early normal pregnancy that was not present in miscarriages. Stimulated MDC1 induced Treg cells in vitro, however, hCG was not involved in this process. Our findings suggest that during normal pregnancy PBDC subsets are differentially regulated dependent on gestational age. Miscarriage seems to be associated with dysregulations in the myeloid PBDC subsets and with disturbances in Treg cell frequencies. Moreover, our results propose an interdependency between MDC1 and Treg cells during early pregnancy. hCG, although shown to impair MDC1 maturation, does not seem to be a key regulator of PBDC alterations during pregnancy.

O76. The role of costimulatory molecules in the pathogenesis of pre-eclampsia

Introduction B7-H1 and B7-H4 molecules belong to the newly discovered immunomodulatory protein family which down-regulates T cell responses. Objectives The aim of the study was to estimate the expressions of B7-H1 and B7-H4 molecules on myeloid and plasmocytoid dendritic cells (DCs) in peripheral blood of patients with pre-eclampsia, normal pregnant women and healthy non-pregnant women. Methods Thirty three patients with pre-eclampsia, 26 normal pregnant women and 12 healthy non-pregnant women were included in the study. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens and B7-H1 and B7-H4 molecules and estimated using flow cytometry. Results The expressions of B7-H1 and B7-H4 molecules were significantly higher on CD1c + myeloid and BDCA-2 + plasmocytoid DCs in the first trimester of pregnancy when compared to the luteal phase of the ovarian cycle. Moreover, the expressions of B7-H1 molecule on CD1c + DCs in the second trimester of normal pregnancy were significantly higher when compared to the first trimester. In the third trimester they decreased when compared to the second trimester. The expressions of B7-H1 molecule on CD1c + myeloid and BDCA-2 + plasmocytoid DCs were significantly lower in pre-eclampsia when compared to healthy third trimester pregnant women. Conclusions It seems that the higher expressions of B7-H1 and B7-H4 molecules on CD1c + myeloid and BDCA-2 + plasmocytoid DCs in the first trimester of pregnancy suggest their role in the immunomodulation during early pregnancy. Lower expressions of B7-H1 molecule on myeloid CD1c + DCs in the third trimester of normal pregnancy may suggest their decreased tolerogenic activities before the labour. It seems possible that the lower expressions of B7-H1 tolerance molecule on CD1c + myeloid and BDCA-2 + plasmocytoid DCs in pre-eclampsia may be associated with the increased inflammatory response which is observed in this syndrome.

The expression of B7-H1 and B7-H4 co-stimulatory molecules on myeloid and plasmacytoid dendritic cells in pre-eclampsia and normal pregnancy

The aim of our study was to estimate the expression of B7-H1 and B7-H4 molecules on myeloid and plasmacytoid dendritic cells (DCs) in the peripheral blood of patients with pre-eclampsia, normal pregnant women and healthy non-pregnant women. Thirty-three patients with pre-eclampsia, 26 normal pregnant women, and 12 healthy non-pregnant women were included in the study. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens and B7-H1 and B7-H4 molecules and estimated using flow cytometry. The expression of B7-H1 and B7-H4 molecules was significantly higher on CD1c+ myeloid and CD303+ plasmacytoid DCs in the first trimester of pregnancy than in the luteal phase of the ovarian cycle (CD1c+B7-H1+: 19.19±10.55% vs. 11.99±6.79%; p<0.05; CD1c+B7-H4+: 12.01±9.15% vs. 3.98±1.97%, p<0.001; CD303+B7-H1+: 4.15±2.38% vs. 1.70±0.87%, p<0.05; CD303+B7-H4+: 5.44±2.93% vs. 2.33±1.54%, p<0.01). Moreover, the expression of the B7-H1 molecule on CD1c+ DCs in the second trimester of normal pregnancy was significantly higher than in the first trimester, but in the third trimester they decreased compared with the second trimester (II vs. I trimester: 32.23±11.30% vs. 19.19±10.55%, p<0.01; III vs. II trimester: 32.23±11.30% vs. 22.39±8.19%, p<0.01). The expression of B7-H1 molecule on CD1c+ myeloid and CD303+ plasmacytoid DCs was significantly lower in pre-eclampsia than in healthy third-trimester pregnant women (CD1c+B7-H1+: 13.78±6.26% vs. 22.39±8.19%, p<0.05; CD303+B7-H1+: 3.66±2.46% vs. 8.65±3.15%, p<0.01). Higher expressions of B7-H1 and B7-H4 molecules on CD1c+ myeloid and CD303+ plasmacytoid DCs in the first trimester of pregnancy suggest the role they play in the immunomodulation during early pregnancy.

The Concentrations of Markers of Bone Turnover in Normal Pregnancy and Preeclampsia

Background. The purpose of our study was to investigate the concentrations of markers of bone turnover in normal pregnancy and preeclampsia. Material and Methods. Forty-five pregnant patients with preeclampsia, 78 healthy pregnant women (26 in first, 26 in the second, and 26 in third trimester of pregnancy), and 20 nonpregnant women were included in the study. Serum concentrations of osteoprotegrin (OPG), receptor activator of nuclear factor kappa B ligand (sRANKL), and the markers of bone turnover, osteocalcin and CrossLaps—degradation products of type I collagen, were determined using the ELISA method. Statistical analysis was performed using Mann–Whitney U-test. Results. The concentrations of sRANKL and OPG were significantly higher in the second trimester of normal pregnancy when compared to the first and the third trimesters and to nonpregnant controls. The concentrations of osteocalcin were significantly higher in the first trimester of physiological pregnancy in comparison with nonpregnant women and with second and third trimesters of pregnancy. The concentrations of CrossLaps were significantly higher in the second trimester of normal pregnancy when compared to the first and third trimester. In preeclampsia, the sera concentrations of osteocalcin and CrossLaps were significantly higher when compared to the third trimester of normal pregnancy. Conclusion. The results suggest that the bone formation is increased in the first trimester, whereas the bone resorption is increased in the second trimester of normal pregnancy. Furthermore, the results suggest that the bone turnover is increased in patients with preeclampsia when compared to healthy normotensive pregnant women.

Placental and spiral artery volume and gray‐scale value assessment via 3‐dimensional sonography in the second trimester

Extreme placental size has been associated with abnormal pregnancy outcomes. The purpose of this study was to establish normal values for placental and spiral artery volume and gray-scale value as assessed via 3-dimensional (3D) sonography in the second trimester. The entry criterion was a documented singleton pregnancy at 14-25 weeks' gestation. Patients with normal pregnancy outcome were stratified into 6 subgroups representing 2-week intervals. Automatic 3D sonographic acquisition of the placental and spiral artery volume and gray-scale value, expressed as a percentage, was obtained. Out of 199 patients with normal pregnancy outcome, the placental volume was between 77.7 and 213.9 cm(3) and the gray-scale value was between 28.6 and 29.2 cm(3) (depending on gestational age). The spiral artery volume adjacent to placenta was between 47.9 and 108.7 cm(3), and the gray-scale value was between 27.5 and 29.5 cm(3). Statistical analysis in each subgroup of patients revealed a significant difference between placental and spiral artery volumes but no difference when the gray-scale value was compared. We defined normal placental and spiral artery volume and gray-scale value in the second trimester of normal pregnancy using 3D sonography.

Evaluation of the utero-placental circulation by three-dimensional Doppler ultrasound in the second trimester of normal pregnancy

Objective. To define normative data with three-dimensional (3D) Doppler ultrasound in the second trimester spiral arteries and placental volume blood flow.Methods. An entry criterion was a documented singleton pregnancy at 14–25 weeks with normal outcome. Each patient had a 3D power Doppler exam. Automatic volume acquisition of the placental and spiral arteries blood flow was obtained. We calculated vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The patients were further divided into subgroups based on two gestational week intervals. The outcome measure was normal pregnancy outcome.Results. One hundred ninety-nine patients were included in this study. Placental and spiral arteries vascular indices slowly increased indicating progressive development of vascular network and increase in the volume blood flow. The range for placental VI was 11.43–14.63, FI was 37.44–40 and VFI was 4.77–6.06. The range for spiral arteries VI was 19–20.91, FI was 39.66–41.1 and VFI was 8.49–8.92. The mean gestational age at delivery was 38.18 weeks.Conclusion. We defined normal 3D power Doppler vascular indices in pregnancies between 14 and 25 weeks of singleton gestation. The study indicated that placental and spiral arteries volume blood flow increased with the advancement of gestational age.

Systemic interleukin-10 concentrations do not alter between the first and second trimester in normal pregnancy

Interleukin 10 (IL-10) is involved in normal fecundity and systemic IL-10 changes during gestation might reflect an immunologic shift at the maternal-fetal interface. Serum IL-10 levels were measured in the first and second trimester of uncomplicated pregnancy in 32 women. The low interassay coefficient of variation of the low adjustor of the IL-10 assay (5.2%) enabled us to detect IL-10 concentrations between 0.50 pg/ml and 4.0 pg/ml. There was no statistically significant difference between serum IL-10 levels in the first trimester (median 1.10; range 0.53-4.60 pg/ml) and second trimester (median 1.05; range 0.64-3.30 pg/ml). IL-10 is not systemically activated to a detectable degree between the first and second trimester of normal pregnancy.

Umbilical-placental blood flow gradient during the early second trimester of pregnancy

To characterize umbilical-placental blood flow gradient during early second trimester of pregnancy. Forty normal pregnant women with a singleton fetus gave their informed consent to participate in this study. All scans were preformed between 12 and 20 weeks' gestation using the simultaneous multigate spectral Doppler imaging (MS-SDI) modality available on the Diasonics Synergy system. The umbilical-placental circulation was scanned at three locations: (1) umbilical artery at the cord insertion, (2) superficial placenta at a point close to the cord insertion, and (3) deep placenta branches at the area adhere to the decidua basalis. The mean value of pulsatility index (PI) and resistance index (RI) were recorded. PI and RI were both significantly lower in the superficial and deep placenta compared with the cord insertion area. No significant differences were found comparing between superficial and deep placenta. In 30 women we found lower values and in 10 women we found a higher value of PI and RI in the superficial and deep placenta compared with the cord insertion. Four of five cases with complicated pregnancies occurred in patients with negative placental gradient compared with only one case with positive placental gradient (p < 0.05). In this preliminary report the umbilical placental blood flow gradient was characterized during the early second trimester of normal pregnancy. The presence of decreasing gradient was established. Absent or opposite gradient between the umbilical artery and the placental vessels was associated with adverse pregnancy outcome.

Umbilical-placental blood flow gradient during the early second trimester of pregnancy

Objective. To characterize umbilical-placental blood flow gradient during early second trimester of pregnancy.Methods. Forty normal pregnant women with a singleton fetus gave their informed consent to participate in this study. All scans were preformed between 12 and 20 weeks' gestation using the simultaneous multigate spectral Doppler imaging (MS-SDI) modality available on the Diasonics Synergy system. The umbilical-placental circulation was scanned at three locations: (1) umbilical artery at the cord insertion, (2) superficial placenta at a point close to the cord insertion, and (3) deep placenta branches at the area adhere to the decidua basalis. The mean value of pulsatility index (PI) and resistance index (RI) were recorded.Results. PI and RI were both significantly lower in the superficial and deep placenta compared with the cord insertion area. No significant differences were found comparing between superficial and deep placenta. In 30 women we found lower values and in 10 women we found a higher value of PI and RI in the superficial and deep placenta compared with the cord insertion. Four of five cases with complicated pregnancies occurred in patients with negative placental gradient compared with only one case with positive placental gradient (p?<?0.05).Conclusions. In this preliminary report the umbilical placental blood flow gradient was characterized during the early second trimester of normal pregnancy. The presence of decreasing gradient was established. Absent or opposite gradient between the umbilical artery and the placental vessels was associated with adverse pregnancy outcome.

Blood myeloid and lymphoid dendritic cells are stable during the menstrual cycle but deficient during mid-gestation

The aim of this study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c +, BDCA-2 +, BDCA-4 +) and the CD1c +:BDCA-2 + ratio in phases of the ovarian cycle and in normal pregnant patients. 18 non-pregnant women and 17 normal pregnant women were included. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies (mAbs) against blood dendritic cell antigens (anti-BDCA-1, BDCA-2, BDCA-4) and estimated using flow cytometry. CD1c +, BDCA-2 + and BDCA-4 + dendritic cells were present in the follicular and luteal phases of the ovarian cycle and in all trimesters of normal pregnancy. The percentages of CD1c + dendritic cells did not differ between the follicular and luteal phases of the ovarian cycle. The percentage of BDCA-2 + dendritic cells was lower in the luteal phase of the ovarian cycle compared with the follicular phase, but the differences were not statistically significant. The CD1c +:BDCA-2 + cell ratio was significantly lower in the luteal phase compared with the follicular phase of the ovarian cycle. The numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, the CD1c +:BDCA-2 + ratio was higher than in the other trimesters of normal pregnancy. All populations of dendritic cells and the CD1c +:BDCA-2 + ratio did not differ in the first and third trimesters of physiological pregnancy. Our results suggest that myeloid and lymphoid dendritic cells are not affected by steroid hormones during the menstrual cycle. The deficiency of peripheral blood dendritic cells observed during the second trimester of normal pregnancy can be associated with their migration to the uterus during the second physiological invasion by cytotrophoblast.

Ultrasonographic Measurement of Fetal Foot Length and Femur/Foot Length Ratio in Second Trimester of Normal Pregnancy in Korean Women

Ultrasonographic Measurement of Fetal Foot Length and Femur/Foot Length Ratio in Second Trimester of Normal Pregnancy in Korean Women

Plasma homocyst(e)ine concentrations in pregnant and nonpregnant women with controlled folate intake

Objective: To assess the effects of folate intake and pregnancy on plasma total homocyst(e)ine concentrations in women during the second trimester of pregnancy compared with young, healthy nonpregnant women. Methods: The diet provided either 450 or 850 μg of folate per day. These levels are approximately the current (400 μg/day) and previous (800 μg/day) Recommended Dietary Allowances for folate in pregnant women. Folate was provided as both food folate (120 μg/day) and supplemental folic acid (either 330 or 730 μg/day) for a period of 12 weeks. Plasma homocyst(e)ine (sum of free and protein-bound homocysteine), serum folate, and erythrocyte folate concentrations were determined weekly. Results: Homocyst(e)ine concentrations were lower in pregnant women during the second trimester of normal pregnancy than in nonpregnant controls, independent of dietary folate intake. The overall mean (± standard deviation) homocyst(e)ine concentration of the pregnant subjects (5.4 ± 1.4 μmol/L) was significantly lower than that observed in the nonpregnant control group (8.7 ± 1.7 μmol/L) ( P < .0001). This difference in homocyst(e)ine concentrations remained constant throughout the 12 weeks of the investigation. Conclusion: The folate intakes in this investigation were adequate to maintain constant homocyst(e)ine concentrations in pregnant and nonpregnant women. The lower homocyst(e)ine concentrations observed in pregnant subjects compared with nonpregnant controls may be a physiologic response to pregnancy.

Plasma Homocyst(e)ine Concentrations in Pregnant and Nonpregnant Women With Controlled Folate Intake

In Brief Objective To assess the effects of folate intake and pregnancy on plasma total homocyst(e)ine concentrations in women during the second trimester of pregnancy compared with young, healthy nonpregnant women. Methods The diet provided either 450 or 850 μg of folate per day. These levels are approximately the current (400 μg/day) and previous (800 μg/day) Recommended Dietary Allowances for folate in pregnant women. Folate was provided as both food folate (120 μg/day) and supplemental folic acid (either 330 or 730 μg/day) for a period of 12 weeks. Plasma homocyst(e)ine (sum of free and protein-bound homocysteine), serum folate, and erythrocyte folate concentrations were determined weekly. Results Homocyst(e)ine concentrations were lower in pregnant women during the second trimester of normal pregnancy than in nonpregnant controls, independent of dietary folate intake. The overall mean (± standard deviation) homocyst(e)ine concentration of the pregnant subjects (5.4 ± 1.4 μmol/L) was significantly lower than that observed in the nonpregnant control group (8.7 ± 1.7 μmol/L) (P < .0001). This difference in homocyst(e)ine concentrations remained constant throughout the 12 weeks of the investigation. Conclusion The folate intakes in this investigation were adequate to maintain constant homocyst(e)ine concentrations in pregnant and nonpregnant women. The lower homocyst(e)ine concentrations observed in pregnant subjects compared with nonpregnant controls may be a physiologic response to pregnancy. Plasma homocyst(e)ine levels are lower in pregnancy irrespective of dietary folate intake.

Fetal sex and variations in kinetic properties of neutrophil alkaline phosphatase during the second trimester of normal pregnancy.

A kinetic parameter (the Vm/Km ratio), an index of neutrophil alkaline phosphatase catalytic efficiency, was studied in 36 women with normal pregnancies at 16-20 weeks' gestation. On each blood sample, determinations were achieved on enzyme extracted from maternal granulocytes by monitoring the phosphohydrolytic activity at 400 nm on a spectrophotometer equipped with software for computation of kinetic parameters. Infant sex was recorded at the delivery for all women included in this study. The recent introduction of NAP as a marker for some pathological pregnancies requires a better knowledge of the behaviour of that enzyme in physiological conditions. Data reported focus attention on fetal sex. It appears to be one of the factors involved in variations of kinetic parameters observed in maternal NAP. Sex-linked differences in placental maturation could explain these results.

Maternal zinc and selenium status in pregnancies with a neural tube defect or elevated plasma alpha‐fetoprotein

Zinc and selenium status was assessed in 30 non-pregnant women, 69 women during normal pregnancy, six with a fetus with a neural tube defect (NTD) and 16 who had a raised plasma alpha-fetoprotein (AFP) but no detectable fetal abnormality. Plasma zinc and selenium concentrations were significantly reduced in the second trimester of normal pregnancy compared with non-pregnant levels. A significant decrease in concentrations of zinc in plasma and selenium in plasma and leucocytes was observed in women in the third trimester compared with women in the second trimester. Women with a fetal NTD and women with an unexplained elevation of plasma AFP had significantly lower leucocyte concentrations of zinc and of selenium. Mean values for plasma zinc, plasma and erythrocyte selenium, and for the activity of glutathione peroxidase in whole blood did not differ from those for normal pregnancy.

Complement factors in fetal and maternal blood and amniotic fluid during the second trimester of normal pregnancy.

Complement factors (C3, C4, C5; Factors B, H and I) were measured in maternal and fetal serum and amniotic fluid obtained from 55 women with singleton pregnancy undergoing diagnostic fetoscopy at 15 to 28 weeks gestation. Maternal serum levels were consistently 10 times higher than fetal levels which in turn were 10 times higher than levels in amniotic fluid. Spearman rank correlation analysis at weeks 20 to 22 (n = 20) revealed a statistically significant correlation between maternal and fetal levels of C3 and Factors B and I, and between maternal and amniotic fluid levels of Factors B and I. A significant increase in fetal levels of C3, C4 and Factor H, and in amniotic fluid levels of C3 and Factor B was seen in relation to advancing gestational age. These differences were not seen in maternal serum during the short interval of pregnancy studied. These data confirm earlier assumptions of fetal synthesis of complement factors, and provide normal reference ranges of complement factors in fetal blood and amniotic fluid.

ZINC AND SMALL BABIES

The content of zinc in peripheral-blood leucocytes decreased from the second trimester of normal pregnancy, but was significantly lower in mothers giving birth to babies who were small for gestational age than in mothers with either normal or small, but appropriate for gestational age, preterm babies. Maternal plasma zinc concentrations were similar in all groups at delivery. Leucocyte zinc correlated positively with muscle zinc levels. These data suggest that maternal tissue zinc depletion is associated with fetal growth retardation.