Clinical trial NCT01148654: The Biomarker Study
Official title: Predicting Preterm Birth and Adverse Neonatal Outcomes With Novel Biomarkers: Identifying Those at Greatest Risk to Allow for Future Therapeutic Trials
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preterm Birth
Preterm Labor
Keywords: preterm birth
preterm labor
PTB
PTL
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: March of Dimes
First posted: 2010-06-22
Enrollment: 1076
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with singleton pregnancies between 22-0/7 and 33-6/7 weeks gestational age who present to the Hospital of the University of Pennsylvania 'Perinatal Evaluation Center' (PEC) complaining of PTL, PPROM, or CI. Group 2: Women who present to Labor and Delivery and will deliver (or have just delivered) a single infant preterm (22-0/7 to 36-6/7 weeks) at HUP.

Brief summary: Preterm birth (PTB) is a leading contributor to perinatal morbidity and mortality. While patients with preterm labor (PTL) are at an increased risk for PTB, not all PTL patients will deliver preterm. In patients with PTB, there is a high prevalence of 'intrauterine inflammation' as demonstrated by a large body of evidence. The presence of inflammation is noted by infiltration of inflammatory cells in the placenta and/or maternal fever in labor and/or elevation of cytokines in the amniotic fluid.

Despite this significant association of inflammation with PTB, identification of women destined to deliver preterm by inflammatory markers in maternal blood has not been successful. To date, it has been difficult to determine which patients with PTL will experience PTB. Identification of biomarkers, such as high sensitivity C-Reactive Protein (hsCRP) as well as others such as sICAM, Pentraxin, sE-Selectin, and CxCL-10 in maternal serum and in placental cord blood, may help to serve three very important clinical aims. 1) Identification of novel biomarkers in maternal serum could help to distinguish those women with PTL who are most likely to deliver PTB. 2) These biomarkers may have a high negative predictive value and thus identify those women who are not likely to deliver preterm, avoiding undue hospital admission and medical therapies. 3) Select biomarkers in the mother and/or in cord blood may serve to identify those preterm neonates at greatest risk for adverse outcome. Through improved identification of these infants, studies with targeted therapies to reduce adverse neonatal outcomes in preterm neonates become feasible.

This study involves a cohort assessment of women at risk for Preterm birth secondary to preterm labor, preterm premature rupture of membranes (PPROM), and cervical insufficiency (CI), between 22-0/7 and 33-6/7 weeks gestational age. We will obtain information regarding patients' pertinent past medical and obstetric history as well as small samples of maternal blood at up to four occasions, small samples of placental cord blood, a maternal saliva sample, and an infant buccal swab. We will follow each of these patient's pregnancy outcomes, and determine if there are any correlations between levels of certain biomarkers and latency to delivery as well as composite adverse neonatal outcomes. In women with PTB \< 37 weeks, cord blood will be collected (as well as maternal saliva and an infant buccal swab) and biomarkers compared between those infants with and without specific adverse neonatal outcomes. Maternal saliva and buccal will be collected on all women and infants enrolled.


Eligibility criteria: Inclusion Criteria:

* Women with singleton pregnancies between 22-0/7 and 33-6/7 weeks gestational age who present to the Hospital of the University of Pennsylvania 'Perinatal Evaluation Center' (PEC) complaining of PTL, PPROM, or CI.
* Women who present to Labor and Delivery and will deliver (or have just delivered) a single infant preterm (22-0/7 to 36-6/7 weeks) at HUP.

Exclusion Criteria:

* Multiple-gestation, major fetal anomaly, fetal demise, severe preeclampsia prior to enrollment, patients on chronic steroid use or immunosuppressive drugs, patients with significant (active) immunological disease (AIDS, SLE), acute febrile illness (such as with active influenza or pyelonephritis), and pregestational diabetes.

Primary outcomes:
measure: preterm birth
timeFrame: enrollment through delivery
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Michal A Elovitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Jamie A Bastek, MD
role: PRINCIPAL_INVESTIGATOR
References: