Maternal–fetal effects of magnesium sulfate on serum osmolality in pre-eclampsia

Objective: To determine the effects of magnesium sulfate therapy on maternal and fetal osmolality in pre-eclampsia. Methods: A total of 34 pre-eclamptic women and 22 normal pregnant women participated in the study. Venous blood was drawn upon admission to the labor and delivery unit. Pre-eclamptic patients received standard magnesium sulfate therapy and had a second sample of venous blood drawn 4 h following the beginning of therapy. Fetal umbilical vein blood was obtained immediately following delivery in both groups. Osmolality was measured using a vapor pressure osmometer. Electrolyte levels were measured with a NOVA 8 biomedical analyzer. Data were analyzed via Student's t test, linear regression and correlation with significance established at p < 0.05. Results:We found no significant difference between the maternal osmolalities of the control and pre-eclamptic groups. Interestingly, fetal cord blood osmolality was significantly lower than maternal osmolality in the normal pregnant women. Sodium levels were also lower, while potassium and ionized calcium levels were higher in the fetal blood. In women with pre-eclampsia treated with magnesium sulfate, there was no difference between the osmolality of the maternal and fetal blood, while potassium and ionized calcium levels were still higher in the fetal blood. Finally, we found no correlation between maternal osmolality and blood pressure. Conclusions: High blood pressure in pre-eclampsia is not associated with altered osmolality. An absence of the normal decrease in fetal osmolality is observed in pre-eclamptic women treated with magnesium sulfate.     

A case–control study of placental lesions associated with pre-eclampsia

ObjectiveTo investigate gross and microscopic placental lesions associated with pre-eclampsia and to determine which lesions are most strongly linked to serious pregnancy complications.MethodsA retrospective case–control study of 173 placentas from women with pre-eclampsia and 173 placentas from healthy normotensive women was conducted.ResultsThe mean placental weight in the pre-eclampsia group was lower than that recorded for the control group (280 g vs 360 g; P < 0.001). Infarcts (65.9% vs 13.2%; P < 0.001) and placental abruption (P < 0.001) were most frequent among women with pre-eclampsia. Microscopic findings showed the following lesions to be associated with pre-eclampsia: hypermature villi, defined by absence of intermediate villi (72% vs 16%; P < 0.001), excessive syncytial knots (90% vs 9%; P < 0.001), decidual vasculopathy (51% vs 8%; P < 0.001), villous fibrosis (6% vs 0%; P < 0.001), erythroblastosis (11% vs 4%; P < 0.01), and avascular terminal villi (9% vs 3%; P < 0.05). Increased syncytial knots, infarcts, basal decidual vasculopathy, hypermature villi, and placental erythroblastosis were still associated with pre-eclampsia after logistic regression modeling.ConclusionPlacental lesions most strongly associated with pre-eclampsia were all causes or expressions of placental hypoxia or ischemia, which appears as the primary mechanism of pre-eclampsia.     

Evaluation of maternal and umbilical serum TNFα levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus

Objective.?The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFα serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients.

Patients and methods.?The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFα concentrations were estimated using a sandwich ELISA assay.

Results and conclusions.?Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFα levels than those in the normotensive controls. Our findings and other reports indicate that TNFα may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor α (TNFα) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental–fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

Relation between first trimester maternal serum leptin levels and body mass index in normotensive and pre-eclamptic pregnancies – Role of leptin as a marker of pre-eclampsia: A prospective case–control study

Objective.?We measured first trimester plasma leptin concentrations in 37 women who subsequently developed pre-eclampsia and 53 normotensive controls to determine the interrelation between leptin and body mass index (BMI) in both groups. We further investigated the association between the risks for pre-eclampsia with maternal leptin levels.

Methods.?Bloods samples were collected at 13 weeks. Non-parametric tests, Spearman's correlation, linear regression analysis and multiple logistic regression analysis were applied in our data.

Results.?1?kg/m² increase in pre-pregnancy BMI was related to a 2.747 (95% CI: 3.242–2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI: 2.873–2.131) ng/ml rise in leptin concentrations among controls. Increased leptin concentration (≥25.3?ng/ml ) in lean women is associated with a 18.8-fold increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8–194, p?=?0.014 ). Leptin treated as a continuous variable is a significant predictor of pre-eclampsia (adjusted OR: 1.08, CI: 1.018–1.133, p?=?0.009).

Conclusion.?Increased leptin concentration can definitely contribute to the prediction of pre-eclampsia in lean women, but this is not the case in overweight women. Further research in terms of longitudinal case–control studies is required to clarify the predictive value of pre-eclampsia.     

Preeclampsia – a risk factor for osteoporosis? Analysis of maternal Sclerostin levels and markers of bone turnover in patients with pre-eclampsia

Introduction: The role of preeclampsia (PE) in affecting bone metabolism could not be clarified in the past years. Recently Sclerostin, a new marker of bone metabolism which is known to have an inhibitory effect on bone formation causing osteoporosis, was discovered. Objective: To investigate serum levels of Sclerostin and markers of bone turnover in women with normotensive pregnancies and pregnancies complicated by PE. Methods: In this prospective study we enrolled 22 women with PE and 22 healthy pregnant women to observe serum levels of carboxyterminal propeptide of type I collagen (PICP), cross-linked carboxyl terminal telopeptide of the type I collagen (ICTP), calcium, phosphate, 25-hydroxyvitamin D and parathyroid hormone. In 16 preeclamptic and 16 healthy pregnant women, serum Sclerostin levels were analyzed. Results: Serum levels of Sclerostin (mean?±?standard deviation: healthy 10.5?±?8.1?pmol/l versus PE 11.5?±?9.4?pmol/l, p?=?0.768), ICTP (healthy 0.3?±?0.2?ng/ml versus PE 0.4?±?0.1?ng/ml, p?=?0.462), PICP (healthy 59.9?±?49.9?ng/ml versus PE 89.0?±?62.0?ng/ml, p?=?0.094), phosphate (healthy 1.1?±?0.2?mmol/l versus PE 1.2?±?0.4?mmol/l, p?=?0.162) and parathyroid hormone (healthy 26.9?±?14?pg/ml versus PE 35.3?±?17.6?pg/ml, p?=?0.08) showed no significant differences between the groups. Significantly lower serum calcium (healthy 2.3?±?0.1?mmol/l versus PE 2.2?±?0.2?mmol/l, p?p?Conclusion: Pregnancies complicated by PE show no signs of high bone turnover and may not lead to a higher risk of osteoporosis in later life.     

Early serum markers of pre-eclampsia: are we stepping forward?

Pre-eclampsia (PE) is a multisystemic disorder of human pregnancy, clinically characterized by hypertension, proteinuria, oedema and platelet aggregation; the syndrome includes vasoconstriction, resulting in maternal hypertension, reduced uterine blood flow, impairment of placenta–vascular endothelial integrity with increased permeability and activation of the coagulation cascade. The aetiopathogenesis of PE remains still unknown, although the central role played by the placenta seems to be crucial. To date, increasing efforts are trying to create an unique and robust biochemical pattern in serum to predict PE. Although the recent data, the definition of an early biochemical pattern in serum to predict PE is still far from reaching the final shape. This stalemate could be due, at least in part, to lack of robust and reproducible methodology (inclusion/exclusion criteria during enrolment, period and type of sample collection, type of sample analysis and interpretation of results) across the different studies. Considering these assumptions, the aim of the current paper is to review the available data about early serum markers of PE.     

Association of folic acid receptor α in maternal serum with neural tube defects

Abstract

Objective: To evaluate whether serum folic receptor α levels are changed in women whose previous pregnancies were complicated with neural tube defects (NTDs).

Methods: This was a case–control study that included 41 women as the control group who had previously had at least one healthy pregnancy and 37 women as the study group who had a previous pregnancy complicated with NTDs. Blood samples were obtained from all of the participants six weeks after the termination of pregnancy or delivery of a baby. Serum folate receptor α concentrations were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit.

Results: The mean concentrations of serum folate receptor α were significantly lower in the NTD cases compared to those in the control group (p?=?0.02). There was no significant difference in mean serum folate titers between the NTD cases and the control group (p?=?0.07).

Conclusion: Low serum folic acid receptor α levels in the current study did not appear to be a regulatory marker of maternal folate homeostasis per se but rather a factor that contributed to the development of NTDs.     

How important is consent in maternal serum screening for Down syndrome in France? Information and consent evaluation in maternal serum screening for Down syndrome: a French study

OBJECTIVES: To evaluate the level of information and informed consent for maternal serum screening (MSS) for Down syndrome (DS) in the second trimester of pregnancy and analyse the exercise of autonomy towards the test by the women concerned. METHODS: We studied the population of pregnant women attending obstetric consultations in two French hospitals over a 3-month period. The women were assigned to three groups according to MSS results for DS: women at high risk of having a child with DS (group 1), women at low risk (group 2) and women who did not undergo the test (group 3). A questionnaire was completed before the medical consultation, to assess the quality of consent before amniocentesis for the group at high risk and before the second-trimester ultrasound scan for the other two groups. RESULTS: We analysed 305 questionnaires for 89, 137 and 79 women belonging to groups 1, 2 and 3 respectively. In total, 123 women (40.3% [IC 95%, 35-46%]) were considered to be well informed; 33 (10%, [IC 95%, 8-12%]) had a high level of knowledge, but made choices not consistent with their stated attitude, and 149 (49.7% [IC 95%, 45-56%]) were considered uninformed. Logistic regression analysis showed that maternal consent depended on three independent components: The score attributed to the doctor for information about MSS (t = 4.216, p < 0.001).Whether the patient belonged to group 1 (t = -2.631, p < 0.009).Educational level (< high-school diploma, high-school diploma or at least two years of higher education after high school) (t = 2.324, p < 0.02). The rate of consent increased with educational level and was highest for the women in group 1 and for those whose doctor had a high information score. CONCLUSIONS: Our findings clearly show that women are provided with insufficient information concerning MSS screening for DS in the second trimester of pregnancy for real and valid consent to be obtained.     

Assessment of maternal–fetal status of some essential trace elements in pregnant women in late gestation: relationship with birth weight and placental weight

Objective: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal–maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population.

Methods: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry.

Results: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2?μg/l, respectively, in maternal venous blood in the pregnant women (n?=?39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p?>?0.05) in the mother–child pairs studied. However, neonatal weight correlated negatively (p?<?0.05) with umbilical venous Cu level. Placental weight correlated positively (p?<?0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood.

Conclusions: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.     

Is there an association between a history of placental abruption and long-term maternal renal complications?

Objective: To investigate whether patients with a history of placental abruption have an increased risk for subsequent maternal long-term morbidity.

Study design: A population-based study compared the incidence of long-term renal morbidity in cohort of women with and without a history of placental abruption. Deliveries occurred during a 25-year period, with a mean follow-up duration of 11.2 years. Renal morbidity included kidney transplantation, chronic renal failure, hypertensive renal disease, etc.

Results: During the study period 99?354 deliveries met the inclusion criteria; 1.8% (n?=?1807) occurred in patients with a diagnosis of placental abruption. Patients with placental abruption did not have higher cumulative incidence of renal related hospitalizations, using Kaplan–Meier survival curve. During the follow-up period patients with a history of placental abruption did not have higher rate of renal morbidity (0.2% versus 0.1%; OR 1.8; 95% CI 0.6–4.8; p?=?0.261). When performing a Cox proportional hazards model, adjusted for confounders such as parity and diabetes mellitus, a history of placental abruption was not associated with renal related hospitalizations (adjusted HR, 1.6; 95% CI, 0.6–4.2; p?=?0.381).

Conclusion: Placental abruption, even though considered a part of the “placental syndrome” with possible vascular etiology, is not a risk factor for long-term maternal renal complications.     

Does marriage between first cousins have any predictive value for maternal and perinatal outcomes in pre-eclampsia?

AIM: To assess the consequences of consanguineous unions between first cousins on the severity of pre-eclampsia and associated perinatal morbidity. METHODS: Six hundred and eighty-six women admitted with a diagnosis of pre-eclampsia were included. The study group consisted of 62 preeclamptic women with a union between first cousins. The remaining patients admitted throughout the same period (n = 624) served as controls. The groups were compared regarding the presence of severe pre-eclampsia, hemolysis elevated liver enzymes low platelets (HELLP) syndrome, eclampsia, placental abruption, hematological complications, renal failure, requirement for antihypertensive or magnesium sulfate treatments, cesarean section for acute fetal distress, birthweight, Apgar scores, perinatal mortality and neonatal morbidity including admission to the neonatal intensive care unit, respiratory distress syndrome, sepsis, convulsions, intracranial hemorrhage, hypoglycemia, hypocalcemia, and jaundice. Student's t-test, chi(2)-test and logistic regression analysis were used for statistical evaluation. RESULTS: Univariate analysis yielded significant differences in parity (P = 0.034), maternal platelet counts (P = 0.02), and maternal serum potassium levels (P = 0.016) among the groups. Respiratory distress syndrome was more frequent (P = 0.043) in infants of unrelated couples. Multivariate analysis, controlling for the confounding factors, revealed that marriages between first cousins had no effect on any of our outcome variables including neonatal respiratory distress syndrome. CONCLUSIONS: Third-degree consanguinity in terms of a union between first cousins seems to have no effect on the development of maternal and perinatal complications in established pre-eclampsia.     

Expression of lipoxin A4, TNFα and IL-1β in maternal peripheral blood,umbilical cord blood and placenta,and their significance in pre-eclampsia

Objective: The purpose of this study was to investigate the expression of lipoxin A₄, TNFα and IL-1β in maternal peripheral blood, umbilical cord blood and placenta, and to assess their significance in pre-eclampsia. Methods: Ninty pregnant women were divided into three groups: a mild PE group (n?=?30), a severe PE group (n?=?30) and a control group (n?=?30). We measured serum levels of lipoxin A₄, TNFα and IL-1β using ELISA. Expression levels of lipoxin receptor (FPR2/ALX) mRNA were compared using quantitative RT-PCR. Results: Mean circulating levels of lipoxin A₄, TNFα and IL-1β in the PE groups were significantly increased compared with matched women in the control group. The ratios of lipoxin A₄/TNFα and of lipoxin A₄/IL-1β in the PE groups were significantly decreased compared with matched women in the control group. No lipoxin A₄ was detected in umbilical cord blood. There was a significant increase in FPR2/ALX mRNA expression in placenta obtained from the PE groups. Conclusions: The level of lipoxin A₄ in maternal peripheral blood may correlate with the expression of FPR2/ALX in placenta. Lipoxin A₄ increased to a lesser degree than either TNFα or IL-1β with progression of PE. This may be one of the reasons why oxidative stress and endothelial dysfunction in severe preeclamptic patients are much more serious that in cases of less severe preeclampsia. Moreover, lipoxin A₄ does not have any effect on the fetus through the placenta. We conclude that supplementing with lipoxin A₄ to ensure adequate levels may be a novel method for the treatment of pre-eclampsia without any effects on the fetus.     

IFPA Senior Award Lecture: Making sense of pre-eclampsia – Two placental causes of preeclampsia?

Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation.Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event.In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause – poor placentation, whereas the latter has an intrinsic cause, ‘microvillous overcrowding’, as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances.     

Association of maternal serum α-fetoprotein with persistent placenta previa

Objective: To evaluate the relationship between maternal serum α-fetoprotein (MSAFP) and the risk of persistent placenta previa.

Methods: We conducted a retrospective cohort study of singleton pregnancies with sonographic evidence of placenta previa at 15?–?20 weeks' gestation, between October 1991 and August 2000. Only pregnancies with MSAFP determination at 15?–?20 weeks' gestation and non-anomalous live-born infants ??24 weeks' gestation were included. Pregnancies in which Cesarean delivery was performed for placenta previa were considered persistent; this was the primary outcome.

Results: Of 275 women with previa at 15?–?20 weeks' gestation, 33 (12%) had previa at delivery. Trend analysis revealed a greater likelihood of persistent previa with increasing MSAFP values (p?=?0.01). Mid-trimester MSAFP <?1 multiple of the median (MoM) was associated with a decreased incidence of persistence of 4%, significantly less than the risk at ??1 MoM (16%; p?=?0.01).

Conclusions: There is an association between increasing MSAFP values and greater likelihood of persistent placenta previa. An MSAFP value <?1 MoM is associated with a reduction in the risk of persistence of previa to delivery.     

Are there any changes in Down Syndrome prevalence in France following the implementation of the measurement of nuchal translucency and maternal serum screening?

OBJECTIVE: To evaluate the impact of prenatal screening for Down Syndrome in France in relation to the important changes in the French prenatal screening policy during the years 1996-1997: measurement of nuchal translucency and maternal serum screening, for all women. PATIENTS AND METHOD: Data are those published from three congenital anomalies registries implanted in Centre-Est, Paris and Bas-Rhin areas, from 1990 to 2001. RESULTS: The livebirth prevalence of Down Syndrome decreased from 1/950 in 1990 to 1/1500 in 2000-2001. This decrease was observed from 1994 onwards but has proved stronger since 1996, in spite of the observed increase in the total prevalence partly explained by changes in the maternal age distribution. Extrapolated to all births in France, the calculated annual number of Down Syndrome births would decrease from 800-900 in 1990 to 500-600 in 2001. Consequently, the proportion of induced terminations following prenatal diagnosis increased from 38.6% in 1990 to 75.5% in 2001. In addition, the mean gestational age of the induced terminations is decreasing. CONCLUSION: It seems reasonable to assume that the observed trends followed the changes in the French national policy for prenatal screening: a mass screening for all women, whatever the maternal age.     

Is maternal anemia associated with small placental volume in the first trimester?

Aim

To clarify whether maternal anemia could reduce placental volume in the early gestation.

Methods

A prospective cross-sectional study was conducted. Consecutive women who visited at 11–13 + 6 weeks’ gestation were enrolled. Subjects were divided into two groups by maternal hemoglobin concentration. Cases with maternal anemia were defined as a hemoglobin level less than 11 g/dl on a blood test (cases), and the others were defined as controls. An ultrasound examination was performed to measure the placental volume and the uterine arterial blood flow. The three-dimensional volume of the placenta using virtual organ computer-aided analysis (VOCAL) technique was acquired by transabdominal ultrasonography. Placental volumes were compared in women with and without anemia.

Results

31 cases and 486 controls were analyzed. Maternal characteristics were not different between two groups except anemia. Placental volumes were 63.6 ± 22.2 and 60.9 ± 22.8 cm³ (ns), uterine arterial RIs were 0.7 ± 0.1 and 0.8 ± 0.1 (ns), and PIs were 1.7 ± 0.5 and 1.8 ± 0.6 (ns) in cases and controls, respectively.

Conclusions

Maternal anemia was not associated with reduced placental volume and uterine arterial Doppler wave form at 11–13 weeks’ gestation.