Fibronectin pattern in the first and second trimester of normal pregnancy

Studied were 25 healthy gravidae in the first or second trimester of pregnancy. Plasma fibronectin (pFN) was assayed in maternal blood serum and the fetal fibronectin (fFN) was quantified in cervico-vaginal secretion. The highest level of fFN was found in the cervico-vaginal secretion of the 1st trimester gravidae while the pFN levels gradually raised to reach its peak between 21 and 24 gestational weeks.     

Combined first trimester nuchal translucency and second trimester biochemical screening tests among normal pregnancies

We prospectively examined whether first trimester nuchal translucency (NT) and second trimester triple test (TT) results are correlated, and determined overlapping and mutual screen-positive rates. Results of NT, TT, amniocentesis and pregnancy outcome were obtained in 508 normal pregnancies. Inter-test correlation was performed by comparing the likelihood ratios (LR). Overlapping of screen-positive cases, of NT and TT, was determined by comparing mutual risks for Down syndrome (DS) livebirth of > or = 1:380. Combined screen-positive rates were evaluated by using summation risk (NT and/or TT exhibiting a risk > or = 1:380) and calculated risk (new risk > or / =1:380, based on multiplication of LR(NT) and LR(TT)). Screen-positive rates between NT and TT differed significantly and when either test showed an increased risk for DS, the probability of the other to predict the same was negligible (p<0.001). Overall screen-positive rates, at a risk > or = 1:380, were 2% and 5.7% for NT and TT, respectively. Summation and calculated combining methods were associated with 7.5% and 2.0% screen-positive rates, respectively. Amniocentesis was performed on 20.7% of the cases, mostly screen-negative ones. Our results showed that, in normal pregnancies, NT and TT do not correlate and that their combined calculated risk in normal pregnancies is associated with a low screen-positive rate of 2.0%.     

Placental transfer of metronidazole in the first trimester of pregnancy

Concentrations of metronidazole and its hydroxy metabolite (I) were determined by a specific chromatographic method in blood, placenta and fetus from 10 women receiving oral metronidazole prior to legal first trimester abortion. In one woman given 2 g of metronidazole 9 hours before abortion, placenta and plasma levels were 6.6 micrograms/g and 13.4 micrograms/ml, respectively. The corresponding values for the hydroxy metabolite (I) were 1.8 micrograms/g and 5.6 micrograms/ml. In nine women receiving 400 mg metronidazole 1 hour before abortion, concentrations of metronidazole in plasma ranged from less than 0.1 to 9.4 micrograms/ml, in placenta from less than 0.1 to 6.3 micrograms/g, and in a fetal tissue from 1.9 to 3.0 micrograms/g. The concentrations of hydroxy metabolite (I) in plasma and placenta and fetal tissue all ranged below those of metronidazole.     

Placental transfer of Zidovudine in first trimester of pregnancy

OBJECTIVE: Zidovudine is one of the most common antiretroviral drugs used to prevent vertical transmission of human immunodeficiency virus. However, it is not recommended for use in the first trimester of pregnancy because of reservations about its potential teratogenicity during the organogenesis phase. The objective of this study was to investigate the placental transfer of zidovudine in the first trimester of human pregnancy. METHODS: Twenty-six pregnant women were given 2 oral doses of zidovudine (200 mg) before first trimester surgical termination of pregnancy. Maternal blood, fetal tissue, and coelomic and amniotic fluid were collected for drug analysis. RESULTS: Zidovudine was detected in all samples of maternal serum and fetal tissue but present in only 7 samples of amniotic and coelomic fluid. Zidovudine concentration in fetal tissue was similar to that of maternal serum. The median fetal/maternal ratio was 0.92 and was not associated with gestational age (r = 0.03, P = .89). CONCLUSION: Zidovudine crossed the first trimester human placenta readily and achieved the level of maternal serum rapidly. Patients who choose to take zidovudine in first trimester of pregnancy should be counseled about the potential fetal effects.     

Placental tissue cyclo-oxygenase 1 and 2 in pre-eclamptic and normal pregnancy.

OBJECTIVE: To investigate the activities of the 2 isoforms of prostaglandin synthetic enzyme cyclo-oxygenase (COX), COX-1 and COX-2, in the placental tissue of women with pre-eclampsia and healthy pregnant women. The relationship between placental lipid peroxidation and the activities of COX-1 and COX-2 was also investigated. METHODS: Tissue specimens were obtained from pre-eclamptic women (20 had severe pre-eclampsia and 38 had mild pre-eclampsia) and 27 healthy pregnant women who underwent cesarean section before the onset of labor. Malondialdehyde (MDA) levels and COX-1 and COX-2 activities were measured in placental tissue homogenates. RESULTS: Mean activities for COX-1 and COX-2 were significantly lower in women with severe pre-eclampsia than in healthy controls (P<0.05 and P<0.01, respectively). COX-1 and COX-2 activities were also lower in women with mild pre-eclampsia than in healthy controls, but the difference was of borderline significance (P=0.049 and P=0.059, respectively). The mean placental MDA level was significantly higher in pregnant women with severe and mild pre-eclampsia than in healthy pregnant women (P<0.01 for both). The correlation analysis showed significant negative correlations between MDA and COX-1 (r=-0.44, P<0.001) and MDA and COX-2 (r=-0.45, P<0.001) in the placental tissue of women with pre-eclampsia. CONCLUSION: These results suggest that COX-1 and COX-2 activities are decreased in the placental tissue of women with pre-eclampsia, probably by oxidative stress.     

Placental retention in late first and second trimester pregnancy termination using misoprostol: a retrospective analysis

Objective: Termination of pregnancy (TOP) for medical reasons is regularly performed using misoprostol. Presence of placental remnants followed by curettage, frequently complicate the procedure. Aim of this analysis is to audit our current policy for medical termination in late first and second trimester, looking at the management of third stage. Methods: A retrospective analysis of patient data was performed. Included were patients that underwent medical TOP in late first or second trimester. Patients were reviewed 6 weeks postdelivery. Characteristics of procedure, patient and pregnancy were analysed to determine factors associated with an increased risk of retained placenta/placental remnants. Results: We included 175 patients. Eighty-five patients (48%) underwent curettage immediately after delivery because of retained placenta or because placental remnants were suspected. Nineteen patients (11%) underwent curettage at later stage. All tissue was examined microscopically for confirmation of placental tissue. Analysis of characteristics of procedure, patients and pregnancies did not identify factors associated with an increased risk of retained placenta or placental remnants. Conclusion: A large number of immediate and late curettages was seen after medical TOP. Misoprostol-dose might play a role and the role of ultrasonographic assessment of the uterine cavity immediately post-placenta-delivery needs to be studied.     

Myomectomy during the first and second trimester of pregnancy

Myomectomy was performed on five symptomatic women in the first and second trimester of pregnancy who were resistant to medical therapy. All the patients ended theirs pregnancies without complications. Three patients of five (60%) underwent spontaneous delivery while the other two patients (40%) had cesarean section. Myomectomy during pregnancy, when necessary, is proving highly effective today.     

Selective reduction of multiple pregnancies in the first trimester or early second trimester.

Nine cases of multiple pregnancies, including 7 sets of triplets and 2 sets of quadruplets, were enrolled for selective fetal reduction between March 1989 and July 1990 at the National Taiwan University Hospital. Under transabdominal or transvaginal ultrasound guidance, potassium chloride was injected into the fetal cardiac chamber to kill the selected fetus during the 10-14th gestational week. The number of fetuses was reduced to two in all cases. No maternal complications occurred during the procedure. Six gravidas have given birth to 6 sets of healthy twins; two pregnancies are progressing smoothly at 26 and 23 weeks of gestation, respectively, and one case underwent spontaneous abortion 4 weeks after the procedure. Selective fetal reduction under ultrasound guidance is an acceptable method of preventing high perinatal mortality and morbidity of immature fetuses in grand multiple pregnancies.     

Placental blood flow mapping in the first trimester of human pregnancy

Human placental circulation in the first trimester of pregnancy remains a subject of scientific debate. Most of the acquired knowledge on the physiological background of maternal-fetal interface relies on old studies, most of them performed in non-hemochorial placentas and using light and electron microscopy for the pathological specimens' evaluation. Recently, some ultrasonographic research in this field, using pulsed-wave and/or colour Doppler, yielded contradictory results. The availability of these non-invasive methods should allow the in vivo investigation of placental circulation since early phases of human pregnancy. A more recent technique - Power Doppler - should be preferred considering its resolution, angle-independence, higher sensitivity for lower velocities and absence of known harmful bioeffects in the early periods of gestation. We provide an overview on first trimester maternal-fetal circulation, assessed by non-invasive techniques, namely by transvaginal power Doppler ultrasonography, trying to contribute to a better understanding of the anatomo-physiological aspects of human placental circulation.     

Placental exosomes and pre-eclampsia: Maternal circulating levels in normal pregnancies and,early and late onset pre-eclamptic pregnancies

Introduction and aimExosomes are a subtype of extracellular vesicle (20–130 nm) released by biological cells under normal and pathological conditions. Although there have been reports of circulating exosomes in normal pregnancy, the relevance of placental-derived exosomes in normal and abnormal pregnancies still needs to be elucidated. The aim of this study was to quantify total and placental-derived exosomes in maternal plasma from normal (N), early onset- and late onset-preeclampsia (PE).MethodPlasma samples were obtained from pregnant women in the third trimester, for the isolation of exosomes by differential ultracentrifugation. Total exosomes were quantified using nanoparticle tracking analysis and immuno-reactive exosomal CD63 quantification. Placental-derived exosomes were quantified using placental alkaline phosphatase (PLAP) as a specific marker. The contribution of placental-derived exosomes to total exosomes in maternal plasma was determined by the ratio of PLAP⁺ exosomes to CD63⁺ exosomes.ResultsThe concentration of total exosomes significantly increased in early onset-PE and late onset-PE compared to N (≤33 weeks) and N (≥34 weeks). The relative concentration of placental-derived exosomes significantly increased in early onset-PE but decreased in late onset-PE compared to N. The ratio of PLAP⁺ exosomes to total number of exosomes significantly decreased in early onset-PE and late onset-PE. A positive correlation between total and placental-derived exosomes were obtained in N (≤33 weeks: Pearson's r = 0.60, ≥34 weeks: Pearson's r = 0.67) and early onset-PE (Pearson's r = 0.51, p < 0.05) with the inverse in late onset-PE (Pearson's r = −0.62, p < 0.01).ConclusionThe differences in the contribution of placental-derived exosomes to total exosomes in maternal circulation suggests a possible pathophysiological role of placental-derived exosomes in pre-eclampsia.     

Lymphocyte subsets in normal and pre-eclamptic pregnancies

Summary. Peripheral blood lymphocyte subsets in normal and preeclamptic pregnancies have been studied by using the monoclonal antibodies OKT3 (T cells), OKT4 (helper/inducer T cells) and OKT8 (suppressor/cytotoxic T cells). In addition the numbers of mononuclear cells bearing la and monocyte antigens have been assessed by using the monoclonal antibodies OKIal and OKM1. No significant differences were found between 10 normal pregnant and 10 non-pregnant subjects. Ten preeclamptic patients were studied and showed an increase in OKT4-positive helper cells. This was significant in terms of percentage of mononuclear cells but not the absolute numbers or the helper/suppressor (OKT4/OKT8) ratio.     

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

Background: 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. Methods: 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. Results: 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). Conclusion: IL-10 is not systemically activated to a detectable degree between the first and second trimester of normal pregnancy.     

Chitotriosidase and YKL-40 in normal and pre-eclamptic pregnancies

OBJECTIVE: To compare macrophage activation in normal and pre-eclamptic pregnancies by determining YKL-40 concentration and chitotriosidase activity in maternal and cord serum. METHODS: In this prospective case-control study samples of maternal peripheral blood and umbilical venous blood were collected from 28 pre-eclamptic and 24 normotensive pregnant women and their newborns. YKL-40 concentration and chitotriosidase activity were determined by enzyme-linked immunoassay and fluorometry, respectively. RESULTS: Chitotriosidase activity in maternal and cord serum and YKL-40 concentration in cord serum were significantly higher in pre-eclamptic pregnancies (P<0.001), but there was no significant difference in maternal serum levels of YKL-40 between the case and control groups (P>0.05). There was a significant positive correlation between diastolic blood pressure and (1) chitotriosidase activity in both maternal and cord serum and (2) cord serum concentration of YKL-40 (r=0.61, r=0.84, and r=0.58, respectively). CONCLUSION: This study may be the first to demonstrate maternal and fetal macrophage activation in pre-eclampsia.     

Activated protein C resistance in normal and pre-eclamptic pregnancies

OBJECTIVES: A lower ratio in the classic activated protein C resistance (APC-R) test has been reported during pregnancy, which has been called 'acquired' APC-R. However, little is known about the cause of the lowered ratio, and whether or not there is a correlation with blood coagulation activation. The primary objective of our study was to determine changes in APC-R levels in each of the trimesters of normal pregnancy. The secondary objective was to confirm whether APC-R levels were lower in pregnancies complicated by pre-eclampsia than in a control group. Finally, this prospective study was performed to investigate the prevalence of APC-R among pregnant women and to elucidate its obstetric consequences. METHODS: We enrolled 35 healthy pregnant women and 47 pregnant women affected by pre-eclampsia in our study. The following laboratory tests were performed: prothrombin time, partial thromboplastin time, fibrinogen levels, antithrombin III, plasmatic fibronectin (as a marker of endothelial damage), haptoglobin (as a marker of intravascular haemolysis), a functional test for APC-R and analysis of factor V Leiden mutation by polymerase chain reaction. RESULTS: The activated protein C sensitivity ratio was lower in the pathological group than in the control group (p = 0.008 and p = 0.02, respectively). Plasmatic fibronectin was found to be higher in the pathological group than in the control group (p = 0.05). Finally, the overall prevalence of factor V Leiden mutation was 5.4%, i.e. 2/35 women (5.7%) in the control group and 3/47 women in the pathological group (6.38%). CONCLUSIONS: The APC ratio decreased after 20 weeks of gestation until week 42. This decrease was most pronounced in the third trimester, in which resistance was demonstrated in 34.2% of control group patients. In pre-eclampsia, we found a greater reduction of the APC ratio than in controls. We hypothesise that this is due to a decrease in the plasmatic levels of coagulation inhibitors and an increase in coagulatory factors.