356: PPROM and PTL phenotypes are characterized by differences in underlying biochemical pathways

Saade, George R.; Boggess, Kim; Sullivan, Scott; Markenson, Glenn; Iams, Jay D.; Coonrod, Dean V.; Pereira, Leonardo; Esplin, M. Sean; Cousins, Larry; Lam, Garrett; Hoffman, Matthew; Fox, Angela; Lueth, Amir J.; Hsu, Chien-Ting; Dykes, Annalise; Dufford, Max T.; Polpitiya, Ashoka D.; Kearney, Paul; Randolph, Todd L.; Boniface, J. Jay; Hickok, Durlin E.; Fleischer, Tracey C.

doi:10.1016/j.ajog.2016.11.614

Cited by 1 publication

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“…Given the substantially higher PTB rate among U.S. Black women (14.4%) as compared to that across the entire population (10.2%), 2 it is important to note that Black participants were represented in both AVERT PRETERM study arms with a proportion (26.5%) nearly double recent population estimates (13.6%). 2 Results in this study population, along with those in two large and similarly diverse studies, 18,20 indicate that the biomarker test will be applicable across the diverse U.S. population. Establishing validated PTB risk with a validated biomarker test enables implementation of e ective PTB prevention strategies among clinically low-risk individuals and, potentially, improvement in patient adherence to usual prenatal care.…”

Section: Discussionmentioning

confidence: 73%

“…Following consent, blood was obtained from prospective arm participants within the window of 19 1/7 -20 6/7 weeks' gestation and samples analyzed using the IGFBP4/SHBG test in a Clinical Laboratory Improvement Amendments-and College of American Pathologistscertified laboratory (Sera Prognostics, Inc., Salt Lake City, UT), as detailed previously. 18,23 Test results were shared with the participant and their care provider. Those with a risk score ≥16.0% (approximately twice the U.S. population PTB risk) were designated as higher-risk then o ered and consented again to receive care management, consisting of twice-weekly nursing contacts to monitor medication compliance and symptom development, and daily progesterone (200 mg intravaginally) and aspirin (81 mg).…”

Section: Methodsmentioning

confidence: 99%

“…Prior studies of the IGFBP4/SHBG predictor have demonstrated that it enriches strongly for severe sPTB and PTB-associated neonatal health outcomes such as hospital and neonatal intensive care unit (NICU) stays and neonatal morbitidy. 18,20,21 As described previously, 22 to avoid masking the clinical benefit of the test-and-treatment strategy by including the large excess of healthy births not expected to be altered by treatment, primary and secondary hypotheses were tested on quantiles of the population corresponding to the earliest births and the longest hospital and NICU stays.…”

Section: Introductionmentioning

confidence: 99%

“…This predictor stratified risk in U.S. women with an accuracy (area under the receiver operating characteristic curve [AUC]) of 0.80. 18,19 Biological links to spontaneous PTB (sPTB) have been proposed to involve IGFBP4 involvement in sensing fetal nutrient delivery and SHBG involvement in proinflammatory signaling within the placenta. 18,20 A risk score threshold corresponding to twice the U.S. population sPTB risk was subsequently validated 21 and shown to significantly stratify higher-and not-higher-risk participants in an extended window of 18 0/7 -20 6/7 weeks' gestation, with a sensitivity and specificity of 88% and 75%, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 Biological links to spontaneous PTB (sPTB) have been proposed to involve IGFBP4 involvement in sensing fetal nutrient delivery and SHBG involvement in proinflammatory signaling within the placenta. 18,20 A risk score threshold corresponding to twice the U.S. population sPTB risk was subsequently validated 21 and shown to significantly stratify higher-and not-higher-risk participants in an extended window of 18 0/7 -20 6/7 weeks' gestation, with a sensitivity and specificity of 88% and 75%, respectively. 19 The objective of the AVERT PRETERM trial was to test whether targeting treatment improves neonatal outcomes for pregnancies deemed by the biomarker to be at elevated PTB risk but lacking traditional PTB risk factors.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal outcomes after maternal biomarker-guided preterm birth intervention: the AVERT PRETERM trial

Hoffman,

Kitto,

Zhang

et al. 2023

Preprint

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1. Background Vaginal progesterone, low dose aspirin and care management (comprising increased outreach and education) has been shown to reduce the rate of prematurity in select populations, but identifying at-risk pregnancies has been problematic. 2. Objective(s) Test the hypothesis that screening singleton, non-anomalous pregnancies lacking traditional clinical risk factors with a validated blood test for preterm birth risk prediction, then targeting those with elevated risk for preventive treatment, would improve neonatal outcomes as compared to a large historical population. 3. Study Design The study took place from June 2018-September 2020 at ChristianaCare Hospital (Newark, DE). Singleton non-anomalous pregnancies with no history of preterm birth were enrolled in a prospective study arm and followed through neonatal hospital discharge. Participants were screened using a serum proteomic test for spontaneous preterm birth risk during a gestational age window spanning 19 1/7-20 6/7 weeks. Pregnancies identified by the test to be at elevated risk for preterm birth (≥16.0%, approximately twice the U.S. population risk) were offered aspirin 81 mg daily, open-label vaginal progesterone 200 mg daily and care management. We compared outcomes for women who screened either low-risk or higher-risk accepting treatment with those in a historical study arm of 10,000 pregnancies. Our co-primary outcomes were neonatal hospital length of stay and an ordinal neonatal morbidity index score based on the occurrence of grade III/IV interventricular hemorrhage, necrotizing enterocolitis (Bell stage II/III), respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity (stage III), sepsis, and neonatal death or neonatal intensive care unit length of stay. Cox proportional hazards survival analysis and ordinal logistic regression were utilized to evaluate outcomes and control for population differences. 4. Results A total of 1463 women were screened and tested before research operations were ceased due to the advent of the COVID-19 pandemic, and three women were subsequently deemed ineligible after screening. Of these, 34.72% (507/1460) were deemed high-risk, with 56.41% (286/507) accepting intervention and 43.59% (221/507) forgoing intervention. The remaining 65.3% (953/1460) were designated as low-risk. Women in the prospective arm were older, more obese, more likely to have hypertension and smoke, and less likely to use opioids compared to women in the historical arm. The primary analyses found that neonates in the prospective arm were discharged from the hospital earlier (P=0.01; hazard ratio, 1.35; 95% confidence interval, 1.08-1.70) and had lower neonatal morbidity index scores (P=0.031; odds ratio, 0.81; 95% confidence interval, 0.67-0.98). Average neonatal hospital length of stay decreased by 21%, and severe neonatal morbidity (neonatal morbidity index ≥3) was reduced on average by 18%. 5. Conclusions Identifying singleton, non-anomalous pregnancies lacking traditional risk factors with a validated proteomic blood test for preterm birth risk and providing treatment to those at risk resulted in improved neonatal outcomes compared to controls in a racially diverse cohort. This test-and-treatment strategy shows promise for ameliorating the impacts of premature birth among individuals in this previously unidentified patient population.

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Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neonatal outcomes after maternal biomarker-guided preterm birth intervention: the AVERT PRETERM trial

Hoffman,

Kitto,

Zhang

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

356: PPROM and PTL phenotypes are characterized by differences in underlying biochemical pathways

Cited by 1 publication

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Neonatal outcomes after maternal biomarker-guided preterm birth intervention: the AVERT PRETERM trial

Neonatal outcomes after maternal biomarker-guided preterm birth intervention: the AVERT PRETERM trial

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