Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT

Summary. Background: Early‐onset hypertensive disorders (HD) of pregnancy and small‐for‐gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding low‐molecular‐weight heparin (LMWH) to aspirin at < 12 weeks gestation reduces the recurrence of HD in women with previous early‐onset HD (pre‐eclampsia, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome and eclampsia) and/or SGA, in the context of inheritable thrombophilia without antiphospholipid antibodies. Patients/methods: In a multicenter randomized control trial (RCT), 139 women included were < 12 weeks gestation. Inclusion criteria: previous delivery < 34 weeks gestation with HD and/or SGA; inheritable thrombophilia (protein C deficiency, protein S deficiency, activated protein C resistance, factor V Leiden heterozygosity and prothrombin gene G20210A mutation heterozygosity); and no antiphospholipid antibodies detected. Intervention: either daily LMWH (dalteparin, 5000 IU weight‐adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone. Main outcome measures: Primary outcomes: recurrent HD onset (i) < 34 weeks gestation and (ii) irrespective of gestational age. Secondary outcomes: recurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention‐to‐treat. Results: Low‐molecular‐weight heparin with aspirin reduced recurrent HD onset < 34 weeks gestation (risk difference [RD] 8.7%: confidence interval [CI] of RD 1.9–15.5%; P = 0.012; number needed to treat [NNT] 12). Recurrent HD irrespective of gestational age was not different between the arms. No women withdrew as a result of adverse effects. Trial Registration: http://www.isrctn.org ) (isrctn87325378). Conclusions: Adding LMWH to aspirin at < 12 weeks gestation reduces recurrent HD onset < 34 weeks gestation in women with inheritable thrombophilia and prior delivery for HD/SGA <34 weeks. However, close monitoring of the mother and fetus remains important throughout pregnancy.     

Association Between Mannose‐Binding Lectin Gene Polymorphisms and Pre‐eclampsia in Brazilian Women

Citation Vianna P, da Silva GK, dos Santos BP, Bauer ME, Dalmáz CA, Bandinelli E, Chies JAB. Association between Mannose‐Binding Lectin gene polymorphisms and pre‐eclampsia in Brazilian Women. Am J Reprod Immunol 2010 Problem Mannose‐binding lectin (MBL) is involved in the maintenance of an inflammatory environment in uterus. High MBL levels have been associated with successful pregnancies whereas low levels are involved in pre‐eclampsia (PE) development. Here, we evaluated MBL2 gene polymorphisms in the structural and promoter regions addressing their association with PE. Method of study DNA samples from 162 control pregnant women and 157 pregnant PE women were genotyped and data compared with demographic and clinical characteristics. Results High frequency of C and D alleles (related to low MBL levels) was observed in PE women when compared to controls (C: 0.08 versus 0.03, P = 0.006; D: 0.10 versus 0.05, P = 0.009). Grouping the MBL genotypes according to phenotype, a higher frequency of OO genotype was observed in PE women when compared to control women (0.15 versus 0.04, P = 0.007). Conclusion Our data suggest that women with genotypes associated with low MBL levels could be potential PE developers.     

Risk factors for pre-eclampsia in Mulago Hospital, Kampala, Uganda

Objective Pre‐eclampsia contributes significantly to maternal, foetal and neonatal morbidity and mortality. The risk factors for pre‐eclampsia have not been well documented in Uganda. In this paper, we describe the risk factors for pre‐eclampsia in women attending antenatal clinics at Mulago Hospital, Kampala. Methods This casecontrol study was conducted from 1st May 2008 to 1st May 2009. 207 women with pre‐eclampsia were the cases, and 352 women with normal pregnancy were the controls. The women were 15–39 years old, and their gestational ages were 20 weeks or more. They were interviewed about their socio‐demographic characteristics, past medical history and, their past and present obstetric performances. Results The risk factors were low plasma vitamin C (OR 3.19, 95% CI: 1.54–6.61), low education level (OR 1.67, 95% CI: 1.12–2.48), chronic hypertension (OR 2.29, 95% CI 1.12–4.66), family history of hypertension (OR 2.25, 95% CI: 1.53–3.31) and primiparity (OR 2.76, 95% CI: 1.84–4.15) and para≥5 (3.71, 95% CI:1.84–7.45). Conclusion The risk factors identified are similar to what has been found elsewhere. Health workers need to identify women at risk of pre‐eclampsia and manage them appropriately so as to prevent the maternal and neonatal morbidity and mortality associated with this condition.     

Antepartum or immediate postpartum renal biopsies in preeclampsia/eclampsia of pregnancy: new morphologic and clinical findings

Background: Preeclampsia (PE) and eclampsia remain leading causes of maternal and fetal mortality worldwide. The kidney is considered the first and most severely affected organ in women with PE/eclampsia. In this study, we analyzed new morphologic features of kidney biopsies and clinical findings in patients with PE or eclampsia at our hospital. Methods: Eight patients with PE/eclampsia underwent renal biopsies during the antepartum (3/8) or postpartum (5/8) period. Maternal clinical findings, major serological indices, neonatal outcomes, and renal histopathologic and immunofluorescent characteristics were reviewed for each case. Results: Most patients had abnormal serum cholesterol (8/8), triglyceride (6/8), albumin (7/8), and uric acid (5/8). The ratio of blood urea nitrogen (BUN) to serum creatinine (SCr) was elevated in all patients. Five of eight newborns survived. Various degrees of morphologic change were present in the renal glomeruli, and were associated with proteinuria. All patients had deposition of complement factor 4 (C4) in the renal glomeruli and seven had deposition of immunoglobulin M (IgM). Conclusion: Endotheliosis, vacuolation of podocytes, proliferation of mesangial cells, and protein casts in the tubule lumens were found in the kidneys of women with PE/eclampsia. Immune depositions of C4 and IgM are major contributors to renal lesions in preeclamptic patients, whose neonates can generally survive. Eclampsia can occur without increased blood pressure.     

Genetic variants, immune function, and risk of pre-eclampsia among American Indians

Citation Best LG, Nadeau M, Davis K, Lamb F, Bercier S, Anderson CM. Genetic variants, immune function, and risk of pre‐eclampsia among American Indians. Am J Reprod Immunol 2012; 67: 152–159 Problem To determine the prevalence in an American Indian population of genetic variants with putative effects on immune function and determine if they are associated with pre‐eclampsia (PE). Method of study In a study of 66 cases and 130 matched controls, six single nucleotide polymorphisms (SNP) with either previously demonstrated or postulated modulating effects on the immune system were genotyped. Allele frequencies and various genetic models were evaluated by conditional logistic regression in both univariate and multiply adjusted models. Results Although most genetic variants lacked evidence of association with PE, the minor allele of the CRP related, rs1205 SNP in a dominant model with adjustment for age at delivery, nulliparity, and body mass index, exhibited an odds ratio of 0.259 (95% CI of 0.08–0.81, P = 0.020) in relation to severe PE (48 cases). The allelic prevalence of this variant was 46.1% in this population. Conclusion Of the six SNPs related to immune function in this study, a functional variant in the 3′UTR of the CRP gene was shown to be associated with severe PE in an American Indian population.