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Biomedical subjects

Thomas F McElrath

Publications and source records attributed to Thomas F McElrath.

10 recordsLinked to original sources

Maternal and Fetal HLA Heterozygosity in Preeclampsia: Insights From a Large Multi-Ancestry Pregnancy Cohort.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic HLA region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4770 PE, 8020 controls; 10,808 maternal, 1982 fetal, including 1848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (> 80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across Class I loci showed a protective effect in preterm PE (OR = 0.81, 95% CI: 0.68-0.97), with a similar pattern for HLA-A heterozygosity (OR = 0.78, 95% CI: 0.64-0.97). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR = 1.36, 95% CI: 1.03-1.80) and preterm PE (OR = 1.73, 95% CI: 1.13-2.74). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE aetiology.

Humans↗

Predictors of compliance with the postpartum visit among women living in healthy start project areas.

OBJECTIVES: Few studies have examined factors associated with compliance with a postpartum visit (PPV). The identification of such factors is of particular importance in populations with high rates of unintended pregnancies and medical complications of pregnancy. This study seeks to determine factors associated with compliance with a PPV among low-income women in the population served by fourteen Healthy Start sites. METHODS: Data from the Healthy Start Survey of Postpartum Women were reviewed to identify variables associated with compliance with a PPV at or beyond 6 weeks. Multiple logistic regression models were created, based on a sociobehavioral model of health services use, to examine which types of factors (demographic, social, enabling or need) are most strongly associated with the use of a PPV. RESULTS: The study population consisted of survey respondents interviewed six weeks or more following delivery. Eighty-five percent of respondents had had a PPV at time of interview. In a multiple regression analysis, enabling factors such as multiple moves (OR (95% CI)=0.34 (0.18, 0.67)), trouble understanding the provider (OR (95% CI)=0.65 (0.43, 0.99)) and appointment reminders (OR (95% CI)=2.37 (1.40, 4.02)) were most strongly associated with a PPV. CONCLUSIONS: This work finds that women with unstable housing, transportation barriers, and difficulties communicating with providers are at risk for not receiving a PPV. This suggests that access to postpartum health services in the Healthy Start communities studied may not be entirely equitable. Policies aimed at improving interconception care will need to address these barriers to accessing health services.

Adult↗

Validation of a formula that calculates the estimated risk of respiratory distress syndrome.

OBJECTIVE: Several groups, including ours, have developed probabilistic models that incorporate both the surfactant-to-albumin ratio (TDx-FLM II) and gestational age to more accurately predict the risk of neonatal respiratory distress syndrome (RDS) and eliminate the current categorical "immature"/"indeterminate"/"mature" interpretation. We validate our model using a separate data set, with the goal of providing the clinician with a risk score. METHODS: The medical records of all women who had TDx-FLM II testing performed at Brigham and Women's Hospital between January 1, 2003, and December 31, 2005, were reviewed to gather a population upon which to validate our previous logistic regression model. Receiver operating characteristic curve and Hosmer-Lemeshow analysis was conducted to determine the performance of our model and another model in this new population. RESULTS: A total of 233 mother-neonate pairs (21 RDS, 212 non-RDS) met criteria for analysis. The receiver operating characteristic analysis illustrated that our previous formula was a strong predictor of the risk of RDS with an area under the curve of 0.902 (95% confidence interval 0.849-0.955). In addition, using the Hosmer-Lemeshow analysis, our formula produced an excellent overall fit (P=.95), whereas another published model was a poor fit to our data (P=.002). CONCLUSION: Our previously derived logistic regression model formula incorporating TDx-FLM II results and gestational age to predict risk of neonatal respiratory distress syndrome was robust and stable over time in an independent data set. The results suggest that the equation can be implemented clinically to assist physicians and patients and used by other institutions after their own internal validation. LEVEL OF EVIDENCE: III.

Humans↗

The use of central neuraxial techniques in parturients with factor V leiden mutation.

The factor V Leiden (FVL) mutation is a leading cause of thrombosis, particularly during pregnancy. During pregnancy, women with thrombotic disorders including FVL are often considered candidates for antepartum anticoagulation with low molecular weight heparin. Pregnancy complications related to thrombosis and the unpredictable timing of labor cause unique challenges with regard to the provision of regional anesthesia. A patient with heterozygotic FVL presenting with thrombotic disease and a complicated anticoagulation status lead us to review 16 additional parturients with FVL. This report focuses on the anesthetic implications that arise in parturients with FVL. We recommend that anesthesiologists be made aware of FVL patients before their due date, anticoagulation with low molecular weight heparin should be transitioned to unfractionated heparin before the 38th gestational week, and multidisciplinary collaborative investigation and care should continue for this disorder.

Adult↗

Neonatal respiratory distress syndrome as a function of gestational age and an assay for surfactant-to-albumin ratio.

OBJECTIVE: Neonatal respiratory distress syndrome (RDS) affects approximately 1% of live births, and the probability of RDS continues to be a major determinant in the timing of delivery. This study was designed to investigate the optimal gestational age-specific cutoff value for a surfactant-to-albumin ratio assay for predicting RDS. METHODS: Amniotic fluid surfactant-to-albumin ratio data were collected prospectively for a 2-year period. Women were included in the study if they delivered within 72 hours of surfactant-to-albumin ratio estimation. RDS was defined by the presence of 2 or more of the following criteria: evidence of respiratory compromise shortly after delivery and a persistent oxygen requirement for more than 24 hours, administration of exogenous pulmonary surfactant, and/or radiographic evidence of hyaline membrane disease. RESULTS: A total of 415 mother-neonate pairs (28 RDS, 387 non-RDS) met criteria for analysis. Both gestational age and surfactant-to-albumin ratio values were independent predictors of RDS. By modeling the odds of RDS by using a logistic regression with gestational age and surfactant-to-albumin ratio values as continuous variables, a probability of RDS of 15% or less can be achieved with a surfactant-to-albumin ratio cutoff of 60 mg or more surfactant/g albumin at 28 weeks of gestation, 50 or more at 30 weeks, 40 or more at 33 weeks, 30 or more at 35 weeks, and 20 or more at 37 weeks. CONCLUSIONS: These data describe a means of stratifying the probability of neonatal RDS using both gestational age and surfactant-to-albumin ratio value and may be a useful model for clinical decision-making. LEVEL OF EVIDENCE: II-2

Albumins↗

Prolonged latency after preterm premature rupture of membranes: an evaluation of histologic condition and intracranial ultrasonic abnormality in the neonate born at <28 weeks of gestation.

OBJECTIVE: The purpose of this study was to evaluate whether infants who were delivered at <28 weeks of gestation after prolonged latency in pregnancies that were complicated by preterm premature rupture of membranes are at increased risk of histologic chorioamnionitis and intracranial ultrasound abnormalities. STUDY DESIGN: A retrospective cohort analysis of 430 singleton infants born at <28 weeks of gestation in five hospitals (January 1991 through December 1993) with at least one of three protocol cranial scans read by a consensus committee and with placental pathologic evidence. Outcome variables were placental (histologic chorioamnionitis, fetal vasculitis) and neonatal (intraventricular hemorrhage, echolucencies, ventriculomegaly). Latency was divided into five intervals, and outcomes in the longer four intervals were compared with those in infants who were delivered at <1 hour after membrane rupture. Each outcome-latency relationship was evaluated in a logistic model that was controlled for confounders. RESULTS: Odds ratios and CIs for each latency interval that was controlled for confounders that included gestational age, maternal race, antenatal steroid and antibiotic administration, and delivery mode show a statistically significant increase in the risk of histologic chorioamnionitis and fetal vasculitis. Models for intraventricular hemorrhage, ventriculomegaly, and echolucencies failed to demonstrate significant differences with increasing latency. CONCLUSIONS: Ascending transcervical infection after preterm premature rupture of membranes is documented by the increasing odds ratios of placental inflammation. The odds of ultrasonically detectable brain abnormalities, however, did not increase with increasing latency.

Adult↗

Contemporary trends in the management of delivery at 23 weeks' gestation.

The objective of this study is to investigate the current understanding of neonatal survival and the willingness to provide aggressive obstetric intervention at the limit of fetal viability among practicing perinatologists in the United States. A pretested survey was mailed to members of the Society for Maternal Fetal Medicine. The survey identified the practitioner's opinion of the lowest limit of viability and gestational ages at which antenatal steroids and cesarean section would first be provided. We also attempted to identify practitioner knowledge of survival at 23 and 24 weeks' gestation and years of perinatal practice. Of the 1244 surveys mailed to members of the Society for Maternal-Fetal Medicine practicing in the United States, 462 practitioners replied for a 37% response rate. Fifty percent considered the lower limit of viability to be 24 weeks' and 44.3% believed the lower limit of viability to be 23 weeks' gestation. Among respondents, the majority estimated a 0 to 10% survival rate at 23 weeks' and 25 to 50% survival rate at 24 weeks. Only 13% of respondents correctly estimates survival at 23 weeks' gestation as >25%, and only 17% correctly estimated survival at 24 weeks' at >50%. Among practitioners, 43.6% would first give antenatal steroids after 24 weeks' gestation but 55.6%would administer steroids before the beginning of week 24. Twenty-eight percent would routinely monitor a fetus less than 24 weeks' gestation. Consistent with this observation, 21% would perform a cesarean section before 24 weeks' gestation. We find that respondents underestimate the consensus in the most recent literature on survival of infants born at 23 to 24 weeks. This underestimation may lead to a limitation in interventions offered.

Attitude of Health Personnel↗

Perinatal outcome after preterm premature rupture of membranes with in situ cervical cerclage.

OBJECTIVE: The presence of a cervical cerclage at the time of preterm premature rupture of membranes (pPROM) could promote clinically evident infection and adverse pregnancy outcome. This cohort study examines whether the presence of cerclage at the time of pPROM is associated with increased maternal or neonatal inflammatory morbidity. STUDY DESIGN: All singleton pregnancies with cerclage and pPROM between 24.0 and 33.9 weeks' gestation at our institution (January 1985-December 1997) were reviewed. Controls (pPROM without cerclage) were matched 2.5:1 by year of presentation. Outcome measures suggest clinical evidence of an infectious response and include maternal admission white blood cell count, time to onset of preterm labor, clinical chorioamnionitis, postpartum fever, neonatal white-matter disease (intraventricular hemorrhage or periventricular leukomalacia) at less than 33 weeks, neonatal sepsis, and neonatal death. RESULTS: One hundred fourteen cases of pPROM and cerclage were matched with 288 controls. The study had power (alpha =.05, power = 0.8) to detect a two-fold difference in incidence of adverse neonatal outcome. Among the mothers, the incidence of clinical chorioamnionitis (14.0% vs 18.8%, P =.26), uterine activity at admission (33.3% vs 32.2%, P =.44), maternal postpartum fever (7.9% vs 7.6%, P =.93) in cerclage versus no cerclage were equivalent. Among the neonates, the incidence of neonatal white- matter disease (15.3% vs 13.7%, P =.75), neonatal sepsis (9.1% vs 6.0%, P =.21), and neonatal death were similar. CONCLUSION: Rates of maternal and neonatal morbidity were similar between both groups. The close overall similarity between the groups strongly suggest clinically insignificant differences between the two groups. These data indicate that a cervical cerclage at the time of pPROM less than 34 weeks does not adversely affect pregnancy outcome.

Adult↗