Preeclampsia: Theories and speculations

Livingston, Jeffrey; Maxwell, B. D.

doi:10.1007/bf03040298

Cited by 9 publications

(4 citation statements)

References 40 publications

(32 reference statements)

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“…It has been called a “disease of theories”[3], [4] due to multiple putative etiologies and risk factors; but placental ischemia seems to play a central role in the pathogenesis, which involves an imbalance of circulating angiogenic factors and endothelial dysfunction [5], [6]. The underlying cause of this ischemia remains unknown; however pregnancy has long been recognized as a distinctive challenge to the maternal immune system.…”

Section: Introductionmentioning

confidence: 99%

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

et al. 2013

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BackgroundThe etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease.MethodsThis study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped.ResultsA nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants.ConclusionThe CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE.

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Section: Introductionmentioning

confidence: 99%

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

et al. 2013

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“…It has also been suggested that maternal immune maladaption to fetal antigens is involved in the pathogenesis of PE, as it may bring about the release of cytokines that causes maternal endothelial cell damage (Livingston and Maxwell, 2003). This immunological hypothesis is further supported by the following epidemiological findings: the incidence of PE is higher in nulliparous women (Campbell et al, 1985) and in women who are less exposed to their partners' antigens (Robillard et al, 1994;Trupin et al, 1996;Smith et al, 1997;Lie et al, 1998;Wang et al, 2002;Saftlas et al, 2003).…”

Section: Introductionmentioning

confidence: 97%

Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies

Tan

Chong

et al. 2008

MHR: Basic Science of Reproductive Medicine

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Pre-eclampsia (PE) is a leading cause of maternal and fetal mortality and morbidity. Structural or functional alterations of human leukocyte antigen (HLA)-G present at the maternal-fetal interface may predispose women to PE. We tested the HLA-G gene for association with PE in a case-control study of 83 PE and 240 normotensive Malay women. HLA-G was amplified in a single-tube multiplex-PCR reaction and genotyped for 18 single nucleotide polymorphisms (SNPs) by multiplex-minisequencing. Case-control comparisons were performed, and associations with disease were expressed as odds ratios (ORs). Risk for PE was significantly associated with fetal allele G*0106 only in multigravid pregnancies (P = 0.002, OR = 5.0, 95% CI = 1.8-13.8). Among multigravid pregnancies, the frequency of PE babies heterozygous or homozygous for G*0106 was also significantly higher compared with normal control babies (P = 0.002, OR = 5.4, 95% CI = 1.9-15.4). Multivariate analyses with adjustment for factors associated with PE revealed similar results (P = 0.003, OR = 10.1, 95% CI = 2.2-46.8). Additionally, a significantly higher frequency of fetal-maternal G*0106 genotype mismatch was observed in PE compared with normal multigravid pregnancies (P = 0.001, OR = 9.6, 95% CI = 2.4-38.7). Thus, paternal HLA-G G*0106 contribution significantly increases risk for PE in multigravidas who do not carry this allele, potentially mediated by a gradual maternal alloimmune response to repeated exposure to the paternal HLA-G variant.

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“…Although these two pregnancy-related disorders have been widely studied, their cause remains unknown. Pathophysiological mechanisms involve the reduction of maternal placental blood flow as of week 20 of gestation, with an increase in peripheral vascular resistance that predominantly takes place in the kidney, liver, and brain [4][5][6][7][8][9]. It has been reported that placenta plays a key role in the pathogenesis of preeclampsia, and it was assumed that, after delivery, its influence in the maternal cardiovascular system would be over.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Diltiazem for the Control of Blood Pressure in Puerperal Patients with Severe Preeclampsia: A Randomized, Single-Blind, Controlled Trial

Arias-Hernández

Vargas‐De‐León

Calzada‐Mendoza

et al. 2020

International Journal of Hypertension

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Background. Postpartum preeclampsia is a serious disease related to high blood pressure that occurs commonly within the first six days after delivery. Objective. To evaluate if diltiazem improves blood pressure parameters in early puerperium patients with severe preeclampsia. Methodology. A randomized, single-blind longitudinal clinical trial of 42 puerperal patients with severe preeclampsia was carried out. Patients were randomized into two groups: the experimental group (n = 21) received diltiazem (60 mg) and the control group (n = 21) received nifedipine (10 mg). Both drugs were orally administered every 8 hours. Systolic, diastolic, and mean blood pressures as well as the heart rate were recorded and analyzed (two-way repeated measures ANOVA) at baseline and after 6, 12, 18, 24, 30, 36, 42, and 48 hours. Primary outcome measures were all the aforementioned blood pressure parameters. Secondary outcome measures included the number of hypertension and hypotension episodes along with the length of stay in the intensive care unit. Results. No statistical differences were found between groups (diltiazem vs. nifedipine) regarding basal blood pressure parameters. Interarm differences in blood pressure (systolic, diastolic, and mean) and heart rate were statistically significant between treatment groups from 6 to 48 hours. Patients in the diltiazem group had lower blood pressure levels than patients in the nifedipine group. Significantly, patients who received diltiazem had fewer hypertension and hypotension episodes and stayed fewer days in the intensive care unit than those treated with nifedipine. Conclusions. Diltiazem controlled arterial hypertension in a more effective and uniform manner in patients under study than nifedipine. Patients treated with diltiazem had fewer collateral effects and spent less time in the hospital. This trial is registered with NCT04222855.

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Preeclampsia: Theories and speculations

Cited by 9 publications

References 40 publications

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies

Efficacy of Diltiazem for the Control of Blood Pressure in Puerperal Patients with Severe Preeclampsia: A Randomized, Single-Blind, Controlled Trial

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