Antiphospholipid antibodies in women at risk for preeclampsia

OBJECTIVE: The aim of this study was to determine whether positive results of tests for any of 5 antiphospholipid antibodies are associated with recurrent preeclampsia among women with a history of preeclampsia in a previous pregnancy. STUDY DESIGN: Second-trimester serum samples were obtained from 317 women with preeclampsia in a previous pregnancy who were being followed up in a prospective treatment trial. The serum samples were measured by enzyme-linked immunoassay for immunoglobulin G and immunoglobulin M antibodies against 5 phospholipids. Positive results were analyzed with regard to preeclampsia, severe preeclampsia, intrauterine growth restriction, and preterm delivery. RESULTS: Sixty-two of the 317 women (20%) had recurrent preeclampsia develop, 19 (6%) had severe preeclampsia, and 18 (5.8%) were delivered of infants with growth restriction. Positive results of tests for immunoglobulin G or immunoglobulin M antiphospholipid antibodies were not associated with recurrent preeclampsia. Positive results for immunoglobulin G or immunoglobulin M antibodies at the 99th percentile were also not associated with preterm delivery. Positive results at the 99th percentile for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results at the 99th percentile for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. The positive predictive values for these outcomes all were approximately 30%. CONCLUSION: Positive results of testing for antiphospholipid antibodies in the second trimester were not associated with recurrent preeclampsia among women at risk because of a history of preeclampsia. Positive results for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. However, the positive predictive values for all these associations were modest. Testing for antiphospholipid antibodies during pregnancy is of little prognostic value in the assessment of the risk for recurrent preeclampsia among women with a history of preeclampsia.     

Antiphospholipid antibodies and pregnancy rates and outcome in in vitro fertilization patients

Objective: To determine the relationship between antiphospholipid antibodies and pregnancy rates (PRs) and outcome among IVF patients.

Design: Prospective collection of all serum samples with assays for immunoglobulin G (IgG), IgA, and IgM antibodies for anticardiolipin, antiphosphatidyl serine, antiphosphatidyl ethanolamine, antiphosphatidyl choline, antiphosphatidyl inositol, antiphosphatidyl glycerol, and anti-phosphatidic acid being done following completion of all treatment cycles.

Setting: A tertiary care teaching hospital.

Patient(s): Seven hundred ninety-three patients attempting to conceive through IVF.

Main Outcome Measure(s): Pregnancy rates (PRs) and pregnancy loss rates relative to each of the various antiphospholipid antibodies that were measured.

Result(s): There were 528 pregnancies for an overall PR of 66%. Pregnancy rates were equal among patients with positive and negative antiphospholipid antibodies for each of the 21 measured antibodies. Use of receiver operator characteristic curves and logistic regression further confirmed that there was no relationship between PRs or outcome based on antiphospholipid antibodies for any definable threshold value.

Conclusion(s): Elevated antiphospholipid antibody levels are not associated with any change in PRs or pregnancy loss rates in patients attempting to conceive through IVF.     

Fetal growth retardation in relation to maternal smoking and weight gain in pregnancy.

Two types of fetal growth retardation were recognized in term infants. One type was characterized by an abnormally low ponderal index (defined as birth weight in grams X 100 divided by crown-heel length in cubic centimeters.) The other type of growth-retarded infants had abnormally short crown-heel lengths for fetal age. Both types were observed under all conditions studied. However, mothers who smoked cigarettes during pregnancy were more likely to have infants with short body lengths for dates, whereas mothers who had low weight gain in pregnancy were more likely to have infants with low ponderal indices. Social group, prepregnancy weight, parity, marital status, and fetal sex were found to be less determinant of fetal growth than were maternal weight gain and smoking habits.     

Anticardiolipin antibodies in unselected pregnant women. Relationship to fetal outcome

Anticardiolipin antibodies (ACLA) have recently been associated with adverse fetal outcome. The prevalence of elevated ACLA has not been studied in unselected pregnant women, however. Twelve hundred unselected pregnant women were screened for IgG ACLA using an assay standardized by the first international workshop on ACLA. Fifteen (1.25%) were positive for IgG ACLA (greater than 3 SD above the mean) but only 0.5% had moderate to high levels of IgG ACLA (greater than 5 SD above the mean). Low levels of IgG ACLA were not associated with increased risk of fetal loss; however, 50% of women with moderate to high levels of antibody had fetal wastage. These findings further support the association of significantly elevated levels of IgG ACLA with fetal loss.     

Thyroid hormone alteration in pre-eclamptic women.

This study sought a possible relationship between pre-eclampsia and thyroid profile. In a case-control setting, total thyroxine (T4), total tri-iodothyronine (T3), free T4, free T3, thyroxine binding globulin (TBG) and thyrotropin (TSH) levels in 39 pre-eclamptic patients were measured and compared with the levels in 42 healthy controls. We examined possible variations with regard to the severity of pre-eclampsia by dividing cases into mild (n = 17) and severe (n = 22) subgroups. Patients with mild pre-eclampsia showed significantly increased free T4 and TSH levels compared to healthy controls. In severe cases, TSH level was higher, but free T3 and free T4 levels were significantly lower than in controls. Other tests returned non-significant differences between the groups. Our findings suggest that primary hypofunctioning of the thyroid can accompany mild pre-eclampsia and possibly contribute to the pathogenesis. Elevated levels of free thyroid hormones in severe cases, however, may have reflected a preceding thyroid disorder.     

Fetal erythropoietin and endothelin-1: relation to hypoxia and intrauterine growth retardation

BACKGROUND: We have examined whether endothelin-1 (ET-1) and erythropoietin (EPO) in amniotic fluid, and EPO in fetal serum obtained by cordocentesis from fetuses with signs of intrauterine growth retardation (IUGR), were correlated to fetal growth and/or chronic fetal hypoxia. METHODS: Amniotic fluid and fetal serum were obtained by cordocentesis from 28 fetuses suspected to have IUGR and subsequently analyzed for EPO and ET-1 by ELISA. These data were correlated to blood gas results and fetal/maternal parameters at delivery. RESULTS: A novel finding was that ET-1 correlated to PO2 in amniotic fluid. The average level of ET-1 in amniotic fluid was 48.3+/-4.7 pmol/L. The results also showed a correlation between EPO levels in amniotic fluid and EPO in fetal serum. Furthermore, EPO correlated weakly to birth weight at delivery. Children with the lowest birth weights had the highest EPO levels. High EPO values, similarly to ET-1, correlated to low pO2 values. The level of EPO in amniotic fluid was 8.0+/-1.6 mIU/ml and in cord blood 29.5+/-9.6 mIU/ml. CONCLUSIONS: The results indicate that ET-1 levels may be a marker for short-term hypoxia, but not for fetal growth, since ET-1 in amniotic fluid was correlated to PO2 at the time of cordocentesis, but not to birth weight. The results also indicate that EPO levels in amniotic fluid and in fetal cord serum are highly correlated, and thus both can be used as markers for fetal growth and chronic hypoxia before the onset of labor.     

Antiphospholipid antibodies and pregnancy: maternal implications

Antiphospholipid antibodies are associated with a spectrum of serious medical conditions. Several of these are of special concern to the obstetrician because they have a tendency to occur during pregnancy. Untreated pregnant women with aPLA appear to be especially prone to thrombotic events, including stroke. Atypically early-onset preeclampsia occurs in a large proportion of women with aPLA and a history of pregnancy loss. Conversely, a modest proportion of women with early-onset preeclampsia have aPLA. Although rare, a syndrome of postpartum pleuropulmonary disease and thrombosis is associated with aPLA. Finally, certain neurologic conditions, such as TIAs and chorea gravidarum, appear to be related to aPLA. It is important to recognize pregnant women with aPLA so they can be appropriately managed in an effort to avoid fetal loss and thromboembolic events.     

Serial plasma fibronectin levels in pre-eclamptic and normotensive women.

OBJECTIVE: Endothelial cell damage has been put forward as an underlying factor for development of pre-eclampsia. This study was carried out to see if fibronectin, which is a marker of endothelial damage, could be used as a marker of pre-eclampsia. METHODS: A longitudinal study was conducted on 100 normotensive primigravidae registered before 20 weeks of gestation. These subjects were followed until delivery and three blood samples were collected, first at registration, i.e. before 20 weeks, second around 28 weeks and third at 36 weeks or later till delivery. Fibronectin levels were assayed by ELISA and women observed for any signs of pre-eclampsia. RESULTS: Fourteen subjects developed pre-eclampsia. Fibronectin levels were observed to rise as pregnancy advanced but the rise was significantly higher in subjects who developed pre-eclampsia. The fibronectin levels were also significantly higher in these 14 subjects even in the first sample, i.e. before 20 weeks of gestation when compared with normotensive subjects (P < 0.01). CONCLUSIONS: Fibronectin levels could be used as an early valuable biomarker for the development of pre-eclampsia.     

Plasma lipid concentrations in pre-eclamptic and normotensive Peruvian women.

OBJECTIVES: Dyslipidemia is thought to be of etiological importance in pre-eclampsia. We studied the relationship between maternal plasma lipid concentrations and risk of pre-eclampsia. METHODS: A total of 125 pre-eclampsia cases and 179 normotensive control subjects were included in this case-control study conducted in Lima, Peru, between August 1997 and January 1998. Postdiagnosis, antepartum plasma lipid profiles were determined by standard enzymatic methods. Logistic regression procedures were used to calculate odds ratios (OR) adjusted for potential confounders. RESULTS: Mean plasma total cholesterol and triglyceride concentrations were, on average, 6% and 21% higher in pre-eclamptics than controls, respectively. High-density lipoprotein (HDL) cholesterol concentrations were, on average, 9% lower in cases than controls. After adjusting for maternal age, prepregnancy body mass index, education, parity and other potential confounders, the risk of pre-eclampsia increased with successively higher quartiles of plasma triglyceride (adjusted OR: 1.00, 1.62, 2.21, 5.00, with the lowest quartile as referent; P-value for trend < 0.001). The association between pre-eclampsia risk and plasma total cholesterol was much less pronounced. In general, there was an inverse association between pre-eclampsia risk and HDL cholesterol concentration (adjusted OR: 1.00, 0.41, 0.50, 0.38, with the first quartile as the referent group; P-value for trend = 0.02). CONCLUSIONS: These findings suggest that high triglyceride and low HDL cholesterol concentrations are important risk factors for pre-eclampsia among Peruvian women.     

Postnatal growth failure in preterm infants: ascertainment and relation to long-term outcome

OBJECTIVE: Traditional measure of postnatal growth failure assessment has poor discriminatory power for long-term outcomes. Our objective was to identify measure of postnatal growth failure associated with long-term outcome in preterm infants born at < 28 weeks' gestation. PATIENTS AND METHODS: Four measures of defining postnatal growth failure at 36 weeks corrected gestational age: (1) weight < 10(th) centile, (2) weight < 3(rd) centile, (3) z score difference from birth > 1 and, (4) z score difference from birth > 2; were compared for their predictive values and strength of association with adverse neurodevelopmental outcomes at 18-24 months. RESULTS: Postnatal growth failure defined as a decrease in z score of > 2 between birth and 36 weeks corrected gestational age had the best predictive values compared to other postnatal growth failure measures, however, it was significantly associated with psychomotor developmental (P=0.006) but not with mental developmental indices (P=0.379). CONCLUSION: Postnatal growth failure defined by z score change influenced psychomotor but not mental tasks in this cohort. This method of ascertainment could be useful to identify infants who might benefit from nutritional interventions.     

Leptin receptor gene polymorphisms in severely pre-eclamptic women.

Variants of the leptin receptor gene (LEPR) may modulate the effect of elevated serum leptin levels in pre-eclampsia. The aim of our study was to evaluate the LEPR gene polymorphisms Lys109Arg (A109G) and Gln223Arg (A223G) in severely pre-eclamptic women. In a case-control study, we analyzed blood samples from 124 severely pre-eclamptic patients and 107 healthy control women by the polymerase chain reaction-restriction fragment length polymorphism method. The Pearson chi2 test was used to estimate odds ratios (OR) and 95% confidence intervals (CI). The association was adjusted for maternal age, pre-pregnancy body mass index and primiparity with logistic regression analysis. Pregnant women with the LEPR 223G allele (223A/G or 223G/G genotype) had almost double the risk of developing severe pre-eclampsia compared with patients with the 223A/A genotype (adjusted OR = 1.92, 95% CI: 1.07-3.41). Genotype variants of LEPR A109G alone did not affect the risk of severe pre-eclampsia. Haplotype estimation of A109G and A223G polymorphisms of the LEPR gene revealed that the G-A haplotype versus other pooled haplotypes was significantly less common in the pre-eclamptic group (p < 0.01), while the G-G haplotype versus others was overrepresented among severely pre-eclamptic patients (p < 0.01), compared with controls. In conclusion, our data indicate that LEPR A223G polymorphism may individually modify the risk of severe pre-eclampsia.     

Plasma adiponectin concentrations and placental adiponectin expression in pre-eclamptic women.

This study was conducted to compare maternal plasma adiponectin concentrations and adiponectin expression in term placentas between normotensive pregnant women and pre-eclamptic women. Plasma adiponectin concentrations were assessed by a sandwich enzyme-linked immunosorbent assay in 81 normotensive pregnant women, 27 pre-eclamptic women and 15 non-pregnant healthy women. The expression of adiponectin in the placentas was assessed by immunohistochemistry. Plasma adiponectin concentrations in normotensive pregnant women did not show a significant change during pregnancy and postpartum compared with non-pregnant women. However, plasma adiponectin concentrations in pre-eclamptic women were significantly (p < 0.05) lower than in non-pregnant and normotensive pregnant women. No immunoreactive adiponectin was detected in the term placentas of normotensive pregnant women, whereas a positive immunostaining for adiponectin was observed in endothelial cells of chorionic vessels in pre-eclamptic women. Our data suggest that decreased plasma adiponectin concentrations may contribute to the pathophysiology of pre-eclampsia and that adiponectin localized in chorionic vessels may play a role in the restoring of endothelial damage in the feto-maternal units of pre-eclampsia.     

Antiphospholipid antibodies and preeclampsia: a case-control study

OBJECTIVE: To assess the association between the occurrence first of preeclampsia and antiphospholipid antibodies. METHODS: We conducted a prospective case-control study of 180 pregnant women with their first incidents of preeclampsia and no histories of thrombosis or systemic autoimmune diseases. Preeclampsia (n = 180) was defined as blood pressure (BP) at least 140/90 mmHg after 20 weeks' gestation and proteinuria at least 0.3 g per 24 hours. Two control subjects were matched to each case (n = 360). They were pregnant women without hypertension or proteinuria and without histories of thrombosis or systemic autoimmune disease. Lupus anticoagulant (activated partial thromboplastin time, diluted thromboplastin time, platelet neutralization procedure) and anticardiolipin antibodies (immunoenzymatic assays) were assessed in both groups, and the coagulation state (levels of thrombin-antithrombin III complexes, fragments 1 + 2 of prothrombin) was also evaluated. The analysis design was a sequential plan with 5% type I error and 95% power. RESULTS: There was no association between antiphospholipid antibodies and preeclampsia. The odds ratio for the association was 0.95 (95% confidence interval 0.45, 2.61). Antiphospholipid antibodies were detected in eight of 180 preeclamptic women and in 19 of 360 controls. In contrast, there was a clear, confirmed activation of coagulation during preeclampsia. CONCLUSION: Despite evidence of a prothrombotic state during preeclampsia, it is unlikely that antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) represent risk factors for preeclampsia among women with no previous preeclampsia and no histories of thrombosis or systemic autoimmune disease.     

Antiphospholipid antibodies and coagulation defects in women with implantation failure after IVF and recurrent miscarriage

Evaluation of patients with IVF implantation failure or recurrent miscarriage often frustratingly fails to elicit any particular cause for their problem. Testing for antiphospholipid antibodies or thrombophilia is commonly carried out, and interpretation of results in the light of the current evidence is extremely difficult. This paper reviews the purported pathogenetic mechanisms and clinical associations between both antiphospholipid antibodies and inherited thrombophilias, and reproductive failure. The current management strategies are also critically evaluated and recommendations are made for optimal, evidence-based clinical practice.     

Birth weight percentile and perinatal outcome: recurrence of intrauterine growth retardation

In 9596 patients followed throughout two pregnancies, recurrence of intrauterine growth retardation (IUGR) was evaluated as a function of previous birth weight percentile and attendant complications of pregnancy. Among 4623 patients with two uncomplicated pregnancies, the prevalence of recurrent IUGR was significantly related to the severity of growth retardation in the first pregnancy (P less than .0001). Those patients with both medical complications and IUGR in the first pregnancy remained at significantly increased risk for recurrent IUGR, even when the second pregnancy was uncomplicated. In second pregnancies, the combination of a previous history of an IUGR neonate and an additional current complication of pregnancy acted synergistically to increase the risk of recurrent IUGR to a level higher than that attributable to either risk factor alone.