Jersey-Placental Abruption Study Research Articles

Diagnosis of Placental Abruption: Relationship Between Clinical and Histopathological Findings

Despite intensive investigation, it is unclear whether the diagnosis of placental abruption should be based on established clinical criteria or histopathological findings. Although the vast majority of placental abruption cases appear to have a chronic etiology, it also remains speculative as to whether abruption is an acute or chronic process. The aim of the present multicenter, case-control study was to assess the concordance between clinical and histopathological diagnostic indicators of placental abruption. A secondary aim was to investigate acute and chronic histological lesions associated with clinical abruption. The clinical and histologic criteria for abruption were compared using data obtained from the New Jersey-Placental Abruption Study. The study subjects, 162 women with a confirmed clinical diagnosis of placental abruption, were matched with 173 controls without placental abruption. Criteria for the clinical diagnosis of placental abruption included painful vaginal bleeding accompanied by nonreassuring fetal status, uterine hypertonicity, evidence of clinically significant retroplacental bleeding, or clot(s) or placental abruption diagnosed on prenatal ultrasound. The pathological criteria for a diagnosis of abruption included hematoma with or without recent or old infarctions, foci of villous compression, fibrin deposition, and hemosiderin-laden histiocytes in cases with older hematomas. Histologic lesions were grouped as acute or chronic histologic lesions. Acute lesions included chorioamnionitis, funisitis, acute deciduitis, meconium-stained membranes associated with amnion necrosis and pigmented macrophages, villous stromal hemorrhage, and villous edema. Chronic lesions included chronic deciduitis, maternal floor decidual necrosis, decidual vasculopathy, placental infarction, villous mal-development with delayed or accelerated maturation, hemosiderin deposition, intervillous thrombosis, and villitis. Of the 162 clinically diagnosed cases, only 30.2% (n = 49) were confirmed as placental abruption based on gross or histological findings, whereas the specificity for a histologic confirmation of abruption was 100%. Among clinically diagnosed cases, the most common indication for a clinical diagnosis of abruption was evidence of retroplacental clot(s) or bleeding (77.1%). Two chronic lesions, placental infarction and decidual vasculopathy, were significantly associated with abruption, but no acute lesions were significantly associated with abruption. The investigators conclude from these finding that there is poor concordance between the clinical and pathological diagnosis of placental abruption. The diagnosis of abruption should be based on clinical criteria such as evidence of retroplacental bleeding or clot(s), ultrasound visualization of abruption, or painful vaginal bleeding accompanied by either nonreassuring fetal status or uterine hypertonocity.

The Normal anticoagulant system and risk of placental abruption: protein C, protein S and resistance to activated protein C

Objective. To examine the association between maternal thrombophilia associated with anticoagulation (proteins C and S and activated protein C resistance ratio, APCR) and risk of placental abruption.Methods. Data were derived from a case–control study – The New Jersey-Placental Abruption Study (2002–2007). Maternal blood was collected from abruption cases and controls and was assayed for the thrombophilias. Decreased protein C, S and APCR was defined as values <5% and <10% among controls.Results. Of a total of 132 cases and 127 controls, 3 were heterozygous for the factor V Leiden mutation (1 case and 2 controls). Mean (± standard deviation) protein C (114.2 ± 25.6 vs. 121.4 ± 27.6; P = 0.009), protein S (39.9 ± 18.4 vs. 35.7 ± 15.2; P = 0.043) and APCR (2.86 ± 0.29 vs. 2.88 ± 0.27; P = 0.039) were different between cases and controls. Abruption cases were associated with an odds ratio of 3.2 (95% CI 1.2, 9.9) in relation to decreased protein C (<Fifth centile). Decreases in both protein S and APCR ratio were not associated with abruption.Conclusions. A decrease in protein C was associated with an increased risk for abruption, suggesting an important role for the physiologic anticoagulant system in the etiology of placental abruption.

Low Birthweight in Relation to Placental Abruption and Maternal Thrombophilia Status

Objective The objective of the study was to evaluate whether the association between low birthweight and placental abruption is mediated through preterm birth or restricted fetal growth and whether these associations were influenced by maternal thrombophilia status. Study Design Data were derived from the New Jersey–Placental Abruption Study, an ongoing, multicenter, case-control study conducted in New Jersey since August 2002. Abruption cases (n = 156) were identified based on a clinical diagnosis, and controls (n = 170) were matched to cases based on parity and maternal race. Low birthweight ( Results Among abruption cases, 60.3% (n = 94) were low birthweight in comparison with 11.2% (n = 19) of controls (OR, 13.7; 95% CI, 7.4-25.2). Furthermore, placental abruption had a significantly increased association with preterm birth in both small for gestational age (OR, 17.4; 95% CI, 4.6-64.9) and appropriately grown fetuses (OR, 15.8; 95% CI, 8.4-29.8). However, the association between abruption and low birthweight were similar between women with and without thrombophilia. Conclusion The association between placental abruption and low birthweight is chiefly mediated through preterm birth, and this association does not appear to be modified by maternal thrombophilia status.

Diagnosis of placental abruption: relationship between clinical and histopathological findings

Objective We evaluated the extent to which histologic lesions bearing a diagnosis of abruption conform to a diagnosis based on established clinical criteria. We further examined the profile of chronic and acute histologic lesions associated with clinical abruption. Methods Data from the New Jersey-Placental Abruption Study – a multi-center, case-control study – were utilized to compare the clinical and histologic criteria for abruption. The study was based on 162 women with clinically diagnosed abruption and 173 controls. We examined the concordance between clinical indicators for abruption with those of a histopathological diagnosis. The clinical criteria for a diagnosis of abruption included (i) evidence of retroplacental clot(s); (ii) abruption diagnosed on prenatal ultrasound; or (iii) vaginal bleeding accompanied by nonreassuring fetal status or uterine hypertonicity. The pathological criteria for abruption diagnosis included hematoma, fibrin deposition, compressed villi, and hemosiderin-laden histiocytes in cases with older hematomas. Acute lesions included chorioamnionitis, funisitis, acute deciduitis, meconium stained membranes, villous stromal hemorrhage, and villous edema. Chronic lesions included chronic deciduitis, decidual necrosis, decidual vasculopathy, placental infarctions, villous mal-development (delayed or accelerated maturation), hemosiderin deposition, intervillous thrombus, and chronic villitis. Results Of clinically diagnosed cases, the sensitivity and specificity for a histologic confirmation of abruption were 30.2% and 100%, respectively. Presence of retroplacental clots remained the single most common finding (77.1%) among clinically diagnosed cases. Among the acute lesions, chorioamnionitis and funisitis were associated with abruption. The only chronic histologic lesion associated with abruption was placental infarctions. Conclusions The concordance between clinical and pathologic criteria for abruption diagnosis is poor. The criteria for diagnosing a clinical abruption should include sonographic visualization of abruption, evidence of retroplacental clots, or vaginal bleeding accompanied by nonreassuring fetal status or uterine hypertonicity.

The effect of maternal thrombophilia on placental abruption: Histologic correlates

Objective. To determine if the histology of placental abruption differs by maternal thrombophilia status.Study design. This was a multicentre, case–control study of women with abruption and delivering at ≥20 weeks' gestation, collected as part of the ongoing New Jersey-placental abruption study. Women were identified by clinical criteria of abruption. Maternal blood was collected postpartum and tested for anticardiolipin antibodies, and mutations in the Factor V Leiden and prothrombin genes. Cases were comprised of women with an abruption and a positive thrombophilia screen. Controls were comprised of women with an abruption and a negative thrombophilia screen. All placental histology was systematically reviewed by two perinatal pathologists, blinded to the abruption status.Results. A total of 135 women with placental abruption were identified, of which 63.0% (n = 85) had at least one diagnosed maternal thrombophilia. There were increases in the rates of meconium-stained membranes (7.9%vs. 2.1%, p = 0.015) and decidual necrosis (4.5%vs. 2.1%, p = 0.023) when a maternal thrombophilia was diagnosed. Although there was no difference in the overall presence of infarcts between the two groups (27.0%vs. 38.3%, p = 0.064), the presence of an old infarct was more common among women with a positive thrombophilia screen (83.3%vs. 44.4%, p = 0.003).Conclusion. Placental abruption with a positive maternal thrombophilia screen is associated with higher rates of old placental infarcts and decidual necrosis compared with abruption when thrombophilia is not diagnosed. These lesions suggest a chronic etiology of placental abruption in the presence of a maternal thrombophilia.

Reduced folate carrier 80A→G polymorphism, plasma folate, and risk of placental abruption

Folate deficiency and maternal smoking are strong risk factors for placental abruption. We assessed whether the reduced folate carrier [NM_194255.1: c.80A-->G (i.e., p.His27Arg)] (RFC-1) polymorphism was associated with placental abruption, and evaluated if maternal smoking modified the association between plasma folate and abruption. Data were derived from the New Jersey-Placental Abruption Study--a multicenter, case-control study of placental abruption (2002-2007). Maternal DNA was assayed for the RFC-1 c.80A-->G polymorphism using a PCR-dependent diagnostic test. Maternal folate (nmol/l) was assessed from maternal plasma, collected immediately following delivery. Due to assay limitations, folate levels at > or =60 nmol/l were truncated at 60 nmol/l. Therefore, case-control differences in folate were assessed from censored log-normal regression models following adjustment for potential confounders. Distribution of the mutant allele (G) of the RFC-1 c.80A-->G polymorphism was similar between cases (52.3%; n = 196) and controls (50.5%; n = 191), as was the homozygous mutant (G/G) genotype (OR 1.1, 95% CI 0.6-2.2). In a sub-sample of 136 cases and 140 controls, maternal plasma folate levels (mean +/- standard error) corrected for assay detection limits were similar between placental abruption cases (63.6 +/- 5.1 nmol/l) and controls (58.3 +/- 4.7 nmol/l; P = 0.270), and maternal smoking did not modify this relationship (interaction P = 0.169). We did not detect any association between the RFC-1 c.80A-->G polymorphism and placental abruption, nor was an association between plasma folate and abruption risk evident. These findings may be the consequence of high prevalence of prenatal multivitamin and folate supplementation in this population (over 80%). It is therefore not surprising that folate deficiency may be rare and that the RFC-1 c.80A-->G polymorphism is less biologically significant for placental abruption.

Low birthweight in relation to placental abruption and maternal thrombophilia status

The objective of the study was to evaluate whether the association between low birthweight and placental abruption is mediated through preterm birth or restricted fetal growth and whether these associations were influenced by maternal thrombophilia status. Data were derived from the New Jersey-Placental Abruption Study, an ongoing, multicenter, case-control study conducted in New Jersey since August 2002. Abruption cases (n = 156) were identified based on a clinical diagnosis, and controls (n = 170) were matched to cases based on parity and maternal race. Low birthweight (<2500 g) was stratified based on preterm birth (<37 weeks' gestation) and small for gestational age (birthweight < the 10th percentile for gestational age). Maternal thrombophilia assessment was based on serum evaluation (protein C and S deficiency, activated protein C resistance ratio, and anticardiolipin antibodies) as well as genetic polymorphisms (methylenetetrahydrofolate reductase, prothrombin gene, and factor V Leiden). Associations were expressed based on odds ratios (ORs) with 95% confidence interval (CI). Among abruption cases, 60.3% (n = 94) were low birthweight in comparison with 11.2% (n = 19) of controls (OR, 13.7; 95% CI, 7.4-25.2). Furthermore, placental abruption had a significantly increased association with preterm birth in both small for gestational age (OR, 17.4; 95% CI, 4.6-64.9) and appropriately grown fetuses (OR, 15.8; 95% CI, 8.4-29.8). However, the association between abruption and low birthweight were similar between women with and without thrombophilia. The association between placental abruption and low birthweight is chiefly mediated through preterm birth, and this association does not appear to be modified by maternal thrombophilia status.

675: The role of factors VIII(c) and XI in placental abruption: For the New Jersey Placental Abruption Study Investigators

675: The role of factors VIII(c) and XI in placental abruption: For the New Jersey Placental Abruption Study Investigators

Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption

Heritable thrombophilias have been implicated as a potential cause of abruption by vascular disruption at the uteroplacental interface. Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been linked to vascular complications outside of pregnancy, which includes stroke. Given the underlying thrombotic nature of abruption, we hypothesized that polymorphisms in the MTHFR gene are associated with abruption. We examined 2 variants in MTHFR: 677C-->T and 1298A-->C in genomic DNA extracted from maternal blood from the New Jersey-Placental Abruption Study, an ongoing, multicenter case-controlled study. We identified 195 women with a clinical diagnosis of abruption (cases) and 189 control subjects who were matched on race/ethnicity and parity. We assessed allele and genotype frequencies and their associations with abruption risk after adjusting for confounders through multivariable logistic regression analysis. The wild-type allele (C) frequency of the 677C-->T variant of MTHFR among cases and control subjects was 69.0% and 64.3%, respectively; the wild-type allele (A) of the 1298A-->C variant was 75.9% and 79.4%, respectively. Distributions of the 677C-->T alleles among control subjects violated the Hardy-Weinberg equilibrium (P = .007); distributions of the 1298A-->C alleles were in equilibrium (P = .825). In comparison to the wild-type genotype (C/C), the homozygous mutant form (T/T) of 677C-->T was not associated with abruption (odds ratio, 0.60; 95% confidence interval [CI], 0.33-1.18). Similarly, the homozygous mutant form (C/C) of the 1298A-->C polymorphism was distributed equally between cases and control subjects (odds ratio, 2.28; 95% CI, 0.82-6.35). Plasma homocysteine and vitamin B12, but not folate, concentrations were elevated in cases compared with control subjects among women with the wild-type genotype of MTHFR 677C-->T (P = .039 for homocysteine; P = .048 for B12; P = .224 for folate). In this population, neither heterozygosity nor homozygosity for the 677C-->T and 1298A-->C variants in MTHFR was associated with placental abruption.

Histologic evidence of inflammation and risk of placental abruption

The objective of the study was to determine whether placental abruption is associated with an increased incidence of histologic chorioamnionitis among singleton gestations and whether this association is dependent on its severity. Data were derived from the New Jersey-Placental Abruption Study, an ongoing, multicenter, case-control study conducted in New Jersey since August 2002. Subjects were women with a clinical diagnosis of abruption, and controls were matched to cases based on parity and maternal race/ethnicity. Two perinatal pathologists, blinded to the case-control status, performed all histologic examination based on standardized protocol. The association between chorioamnionitis and abruption was quantified based on odds ratio (OR) with 95% confidence interval (CI), after adjustment for potential confounders, and all analyses were stratified based on preterm birth (less than 37 weeks) status. At preterm gestations (n = 141), chorioamnionitis was present in 30.8% and 12.5% of abruption cases and controls, respectively (OR 3.6, 95% CI 1.7 to 10.5). At term gestations (n = 205), the corresponding rates were 34.6% and 20.4%, respectively (OR 2.8, 95% CI 1.3 to 6.1). Severe chorioamnionitis was 7.2 (95% CI 1.6 to 20.1) and 18.3 (95% CI 2.2 to 150.4) times more common in abruption patients at preterm and term gestations, respectively. Histologic chorioamnionitis is associated with placental abruption. The association was strongest in the presence of severe chorioamnionitis at term and, to a lesser extent, at preterm gestations. These observations suggest that the histologic findings in abruption are accompanied by severe inflammation, in both preterm and term gestations.

The influence of maternal cigarette smoking on placental pathology in pregnancies complicated by abruption

The purpose of this study was to evaluate the effect of maternal cigarette smoking on placental histology in women with abruption. Data were derived from the New Jersey-Placental Abruption Study (NJ-PAS)--an ongoing, case-control study, conducted since August 2002 in 2 large hospitals in NJ. Abruption cases were identified based on a clinical diagnosis. Histologic evaluations were performed by 2 perinatal pathologists who were blinded to the abruption status. Maternal smoking during pregnancy was determined based on patient's self-report. Among abruption cases, histologic findings were compared between smokers and nonsmokers, and the association expressed as odds ratio (OR) with 95% confidence interval (CI). All analyses were adjusted for potential confounders. A total of 189 abruption cases were available for analysis, of which 10.6% (n = 20) were smokers. Intervillous thrombus was more common in women who smoked (20%) than in nonsmokers (3.0%) (OR, 17.5; 95% CI, 3.1-99.4). However, placental infarcts were seen less frequently among smokers than nonsmokers (10.0% vs 32.5%; OR, 0.2; 95% CI, 0.1-0.8). These findings suggest that different pathologic mechanisms may be responsible for the histologic findings between smokers and nonsmokers diagnosed with placental abruption.

Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: Risk of placental abruption

Objectives: Methionine synthase reductase (MTRR) and betaine-homocysteine S-methyltransferase (BHMT) are two enzymes that regulate homocysteine metabolism. Elevated homocysteine (hyperhomocysteinemia) is associated with adverse pregnancy outcomes and vascular disease. We assessed whether polymorphisms in MTRR (66A → G; I22M) and BHMT (742G → A; R239Q) were associated with abruption. We further evaluated whether homocysteine levels differed between cases and controls for MTRR and BHMT genotypes. Methods: Data were derived from the New Jersey Placental Abruption Study (NJ-PAS)—an ongoing, multicenter, case-control study since August 2002. Women with a clinical diagnosis of abruption were recruited as incident cases ( n = 196), and controls ( n = 191) were matched to cases based on maternal race/ethnicity and parity. Total plasma homocysteine concentrations were evaluated in a subset of 136 cases and 136 controls. DNA was genotyped for the MTRR and BHMT polymorphisms. Results: Frequencies of the minor allele of MTRR were 40.8% and 42.2% in cases and controls, respectively (adjusted OR 0.79, 95% CI 0.45, 1.40). The corresponding rates for BHMT were 33.9% and 31.7%, respectively (adjusted OR 1.93, 95% CI 0.99, 4.09). Distributions for the homozygous mutant form of MTRR were similar between cases and controls (OR 1.18, 95% CI 0.62, 2.24). The rate of homozygous mutant BHMT genotype was 2.8-fold (OR 2.82, 95% CI 1.84, 4.97) higher in cases than controls. Stratification of analyses based on maternal race did not reveal any patterns in association. Conclusions: In this population, there was an association between the homozygous mutant form of BHMT (742G → A) polymorphism and increased risk for placental abruption.

Placental abruption is associated with histologic evidence of inflammation: The New Jersey-Placental Abruption Study

INFLAMMATION: THE NEW JERSEY-PLACENTAL ABRUPTION STUDY CARL NATH, JOHN SMULIAN, SUSAN SHEN-SCHWARZ, LILLIAN KAMINSKY, CANDE ANANTH, University of Medicine and Dentistry of New Jersey, Obstetrics, Gynecology and Reproductive Sciences, New Brunswick, New Jersey, Saint Peter’s University Hospital, New Brunswick, New Jersey OBJECTIVE: Placental abruption has been associated with vascular dysfunction and placental inflammation. Recent studies suggest a strong heterogeneity in the clinical pathways that lead to abruption in preterm and term gestations. We hypothesized that placental abruption is associated with an increased incidence of histologic chorioamnionitis. Our objective was to determine if this association was dependent on the severity of chorioamnionitis. STUDY DESIGN: Data were derived from the New Jersey-Placental Abruption Study, an ongoing, multicenter, case-control study conducted in New Jersey since August 2002. Cases (n=137) were identified based on a clinical or histologic diagnosis of abruption, and controls (n=154) were matched to cases based on parity and maternal race. Histologic evaluation was performed by two perinatal pathologists who were blinded to abruption status. Preterm birth was defined as !37 weeks and placental grading of chorioamnionitis was based on standardized terminology. The association between chorioamnionitis and abruption was quantified based on odds ratio (OR) with 95% confidence interval (CI). RESULTS: The incidence of histologic chorioamnionitis was 31.3% for preterm abruption and 34.2% for term abruption. There was an increased odds of abruption being associated with severe chorioamnionitis. CONCLUSION: Severe histologic chorioamnionitis was associated with abruption. This finding suggests that inflammation plays a significant role in the pathway that leads to abruption both in preterm and term gestations.

Is the risk of thromboembolism increased in siblings and parents of women with placental abruption? The New Jersey-Placental Abruption Study

OF WOMEN WITH PLACENTAL ABRUPTION? THE NEW JERSEY-PLACENTAL ABRUPTION STUDY MORGAN PELTIER, CANDE ANANTH, YINKA OYELESE, ANTHONY VINTZILEOS, University of Medicine and Dentistry of New Jersey, Obstetrics, Gynecology and Reproductive Sciences, New Brunswick, New Jersey OBJECTIVE: To determine if there is increased risk of thromboembolic events among firstdegree relatives (siblings and parents) of women who have suffered a placental abruption. STUDY DESIGN: Information about thromboembolic diseases in siblings and parents of women with abruption cases and controls were derived from an ongoing, case-control study, the New Jersey-Placental Abruption Study (NJPAS). Thromboembolic disease was defined as a history of embolism, deep vein thrombosis, myocardial infarction, or stroke. Associations were expessed using odds ratio (95% confidence interval). RESULTS: Rates of thromembolic events amongst male relatives were similar between abruption cases and controls. However, female relatives of cases were at significantly higher risk for thromboembolic disease. This difference was largely due to much greater rates of thrombotic disease in sisters of women with placental abruption (OR 9.1, 95% CI 1.1, 73.7). No difference in risk of thromboembolic disease was detected between mothers of cases and mothers of controls. CONCLUSION: These results underscore that abruption is highly correlated with thrombembolism in the patient’s sisters, but not her brothers or parents. This suggests that placental abruption may share a common genetic factor with other vascular diseases that has penetrance only in women.

The effect of cigarette smoking on placental abruption histology: The new jersey-placental abruption study

The effect of cigarette smoking on placental abruption histology: The new jersey-placental abruption study

Risk of placental abruption in relation to variants in betaine-homocysteine S-Methyltransferase and methionine synthase reductase genes: The New Jersey-Placental Abruption Study

Hyperhomocystenemia is associated with adverse pregnancy outcomes and vascular disease. Betaine-homocysteine S-Methyltransferase (742G→A; BHMT) and Methionine Synthase Reductase (66A→G; MTRR) are 2 enzymes that regulate homocysteine (tHCY) metabolism. We assessed if mutations in BHMT and MTRR are associated with abruption. We further evaluated if tHCY differed between cases and controls for each BHMT and MTRR genotypes.

Is the association between placental abruption and low birthweight dependent on thrombophilia status?: The New Jersey-Placental Abruption Study

Is the association between placental abruption and low birthweight dependent on thrombophilia status?: The New Jersey-Placental Abruption Study

Polymorphisms of the methylenetetrahydrofolate reductase gene and placental abruption: The New Jersey-Placental Abruption Study

PLACENTAL ABRUPTION: THE NEW JERSEY-PLACENTAL ABRUPTION STUDY CANDE ANANTH, MORGAN PELTIER, CELESTE DEMARCO, DARIOS GETAHUN, RIMA ROZEN, JOHN SMULIAN, University of Medicine and Dentistry of New Jersey, Obstetrics, Gynecology and Reproductive Sciences, New Brunswick, New Jersey, McGill University, Human Genetics, Pediatrics and Biology, Montreal, Quebec, Canada OBJECTIVE: To examine associations between MTHFR 677C/T and 1298A/T polymorphisms and placental abruption. STUDY DESIGN: We examined 2 variants in MTHFR: 677C/T and 1298A/T in genomic DNA extracted from maternal blood. Subjects were recruited to the New Jersey-Placental Abruption Study, an ongoing, multicenter case-control study. We identified 168 women diagnosed with abruption (cases), and 162 controls. We assessed allele and genotype frequencies, and their associations with abruption risk. Plasma concentrations of total homocysteine, folate and vitamin B12 were also compared between cases and controls. RESULTS: The wild-type allele frequency of the 677C/T variant among cases and controls was 67.9% and 63.3%, respectively, and that of the 1298A/C variant was 74.9% and 78.0%, respectively. Among women with absence of the homozygous 677C/T mutation, mean homocysteine and vitamin B12 were elevated in cases than controls (P=0.041 and P=0.035, respectively). CONCLUSION: In this population, the MTHFR 677C/T and 1298A/T were not associated with abruption.