Personalized Care for Prenatal Stress Reduction & Prevention of Preterm Birth (PTB) Disparities

Launched by UNIVERSITY OF NORTH CAROLINA, CHAPEL HILL · Apr 3, 2025

Keywords

ClinConnect Summary

This clinical trial, called PTBCARE+, is designed to see if a personalized support program can help reduce stress and lower the risk of preterm birth for pregnant individuals who are at a higher risk of delivering early. The study will compare two groups: one that receives the PTBCARE+ support program, which includes stress-reduction tools and online resources, and another that receives standard prenatal care without these extra supports. The researchers want to find out if those in the PTBCARE+ program report feeling less stressed during pregnancy and if it leads to healthier deliveries close to the expected due date.

To participate, individuals must be pregnant with a single baby between 8 and 19 weeks of pregnancy and have certain risk factors that make them more likely to have a preterm birth, such as a history of high blood pressure or previous preterm delivery. Participants will visit the clinic a couple of times during pregnancy for surveys and health checks, and those in the PTBCARE+ group will receive additional tools and resources to help them manage stress. This study is important because it aims to empower expectant mothers by providing support tailored to their specific needs, potentially improving outcomes for both them and their babies.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Viable, singleton pregnancy, 8+0 to 19+6 weeks, dated by last menstrual period ± ultrasound using standard obstetric criteria per American College of Obstetricians and Gynecologists.
• • Gestational age at first ultrasound by last menstrual period (LMP) / Ultrasound method / Measurement agreement with LMP required • Up to 8 weeks 6 days / crown rump length / ± 5 days
• • 9 weeks 0 days to 13 weeks 6 days / crown rump length / ± 7 days
• • 14 weeks 0 days to 15 weeks 6 days / standard fetal biometry / ± 7 days
• • 16 weeks 0 days to 19 weeks 6 days / standard fetal biometry / ± 10 days
• • Gestational dating / fetal viability must be confirmed by ultrasound prior to enrollment / randomization.
• • Ultrasound report must include documentation of normal fetal heart rate of ≥ 120 beats per minute, or subsequent medical record documentation of auscultation of fetal heart rate ≥ 120 beats per minute.
• • Viability must be confirmed / re-confirmed within 7 days of randomization.
• • If initial consent occurs early in pregnancy and V1/randomization occur later, viability must be reconfirmed to ensure ongoing eligibility prior to initiating V1 activities (including surveys) and proceeding with randomization.
• • 2. No signs or symptoms of, or clinical diagnosis of, evolving miscarriage, active preterm labor, preterm prelabor rupture of membranes at the time of enrollment.
• • Cervical dilation at the time of enrollment is an exclusion criterion. However, cervical evaluation and digital cervical exam is not required prior to enrollment.
• • (3a) High a priori risk for medically indicated preterm birth - must meet at least one of the following 3 criteria (maternal medical history, prior pregnancy history, or moderate risk factor history)
• * miPTB criteria #1: Maternal Medical History - any one of the following:
• • o Known chronic hypertension requiring medications in the 3 months prior to conception or prior to 22 weeks gestation.
• • o At least 2 blood pressure readings 6 hours apart, \<20 weeks gestation, with systolic ≥ 130 mmHg or diastolic ≥ 80 mmHg \*regardless of need for medication or formal diagnosis of hypertension in chart\*
• • o Pre-gestational diabetes mellitus.
• • Diabetes diagnosed \<20 weeks gestation.
• * Maternal chronic or sub-acute renal disease, including chronic kidney failure, chronic renal insufficiency, glomerulonephritis, lupus nephritis, defined as any:
• • \*biopsy proven chronic renal disease history; and/or
• • \*serum creatinine ≥ 1.1 mg/dL at any time during pregnancy prior to enrollment, in the absence of other identifiable transient factors per clinician's assessment (e.g., extreme dehydration, cystitis, pyelonephritis); and/or
• • \*chronic proteinuria, defined as baseline urine protein:creatinine ratio ≥ 0.30 mg/dL or 24 hour total urine protein ≥ 300 mg in the absence of other identifiable transient factors per clinician's assessment (e.g., extreme dehydration, cystitis, pyelonephritis)
• • \*Systemic Lupus Erythematosus
• • Antiphospholipid Antibody Syndrome
• • miPTB criteria #2: Prior pregnancy history - any ONE of the following: o Previous pregnancy complicated by preeclampsia or hypertensive disorders of pregnancy at any gestational age, in a singleton gestation; the fetus must not have had major structural anomalies or aneuploidy.
• • o Previous history of stillbirth ≥ 16+0 weeks in a singleton gestation; the fetus must not have had major structural anomalies or aneuploidy. The stillbirth etiology must not have been attributed to physical trauma (e.g., domestic violence, motor vehicle accident) or illicit drug use (e.g., cocaine use leading to abruption and stillbirth).
• • miPTB criteria #3: Any two or more of the following moderate risk factors: o Nulliparity, defined as no prior pregnancy to reach at least 20 weeks gestation note that this is the traditional / classic definition of 'nulliparous' and that there is overlap between nulliparity as defined this way and 'preterm birth' due to cervical insufficiency, which allows for deliveries in the 16-19 week gestational age range to be considered as 'preterm births'
• • o Obesity: current or pre-pregnancy body mass index ≥30 kg/m\^2
• • o Family history: first degree relative with a history of preeclampsia
• • o Advanced maternal age: maternal age ≥ 35 years at estimated date of confinement
• o Prior adverse obstetric history - one or more of the following:
• • - history of low birth weight or small for gestational age baby in a singleton gestation, defined as weight \<10% for gestational age and fetal sex; the fetus must not have had major structural anomalies or aneuploidy.
• • - history of adverse pregnancy outcome in a singleton gestation; the fetus must not have had major structural anomalies or aneuploidy.
• • o Long interpregnancy interval: ≥ 10 year (3650 day) pregnancy interval, defined as the time (in days) between the date of delivery of the last pregnancy to reach ≥ 20 weeks gestation and the first day of the last menstrual period for the current pregnancy.
• • o Black or African-American race (as a proxy for underlying racism) - self-reported. Participants who self-identify as being of more than one racial group will be considered to be of Black race for the purposes of this criterion if one of the racial groups is Black or African-American.
• • Low socioeconomic status, defined as one or more of the following: housing or food insecurity noted in chart within the last year, self-pay or Medicaid insurance, less than high school education
• • and/or
• • (3b) High a priori risk for spontaneous preterm birth - must meet at least one of the following 2 criteria (prior pregnancy history or current pregnancy course)
• • sPTB criteria #1: Prior pregnancy history
• • EITHER a history of a delivery of a singleton, non-anomalous baby between 16+0 and 34+6 weeks gestation or delivery of a twin, non-anomalous pregnancy between 160 /7and 276 /7 weeks gestation due to spontaneous preterm labor, preterm premature rupture of membranes, cervical insufficiency, or placental abruption - Chart documentation of prior preterm birth, the gestational age of the prior preterm birth (referred to as the 'qualifying delivery') should be determined. If the gestational age at delivery is obtained directly from the medical record and more than one gestational age appears, the greater of the two will be used assuming that neither is the 'source document' (i.e. an ultrasound report with a due date, a c-section report, a delivery note, etc).
• • Use the following table as a validation of the previous delivery. For example, if the infant was male and weighed more than 2763 grams (6 pounds, 1.5 ounces) then the patient would be ineligible based on history of a preterm birth criteria. This table should only be used to determine whether the qualifying delivery is most likely to be preterm less than 35 weeks gestation when the gestational age CANNOT be verified/calculated by review of the medical records or is not available in the medical records.
• • Gestational age 90th percentile - boys 90th percentile - girls 33 weeks \> 2488g 5 lbs 7.8 oz \> 2116g 4 lbs 10.6 oz 34 weeks \> 2763g 6 lbs 1.5 oz \> 2379g 5 lbs 3.9 oz 35 weeks \> 3084g 6 lbs 12.8 oz \> 2661g 5 lbs 13.9 oz
• • Documented history of a prior pregnancy complicated by asymptomatic cervical shortening \<25mm between 16+0 and 23+6 weeks gestation or cervical dilation ≥ 0.5cm requiring cervical cerclage placement prior to 24+0 weeks gestation, even if delivery ultimately occurred ≥ 35 weeks gestation or at term.
• • • sPTB criteria #2: Current pregnancy course
• • Asymptomatic cervical shortening \<25mm in the current pregnancy, diagnosed by transvaginal ultrasound that is performed ≥14+0 weeks gestation, per Registered Diagnostic Medical Sonographer(RDMS) certified Sonographer or physician with transvaginal ultrasound training program (or similar) qualifications
• • Cervical cerclage in situ in the current pregnancy due to concern for risk of preterm birth, at the discretion of the primary obstetric provider
• • (4) Ability to provide written, informed consent in English or Spanish
• • (5) Planned prenatal care at the University of North Carolina at Chapel Hill obstetrics clinics and planned delivery at the University of North Carolina Women's Hospital (Chapel Hill, NC).
• Exclusion Criteria:
• • 1. Participation in another intervention based clinical trial during pregnancy that is deemed, at the discretion of the investigative team for the current study or the other concurrent study, to conflict with this research and/or confound the study results.
• • o There are some concurrent studies, even those designed to test an intervention, which may be compatible with the current study; this will be reviewed by the investigative leadership team on a case-by-case basis.
• • 2. Previous participation in the PTBCARE+ program in another pregnancy, with randomization to the PTBCARE+ (active intervention) group.
• • 3. Current, ongoing, illicit drug use ≥ 12 weeks gestation.
• • Use of tobacco and/or marijuana products is not an exclusion.
• • Receiving treatment for opioid use disorder with methadone, suboxone, or similar in an approved treatment program is not an exclusion.
• • 4. History of radical trachelectomy
• • 5. Planned voluntary termination of pregnancy.
• 6. Heavy vaginal bleeding or large subchorionic hemorrhage - defined as:
• • Bleeding as primary reason for unplanned clinic evaluation or emergency room visit within 14 days of potential enrollment
• • Subjective bleeding accompanied by ≥ 4 point drop in the hematocrit within 14 days of potential enrollment
• • Subchorionic hemorrhage or abruption on formal ultrasound with a volume ≥ 64 cubic cm (4cm x 4cm x 4cm) within 14 days of potential enrollment
• • 7. Major congenital anomaly such as major structural deficit of the heart, lungs, brain, or other major organ system
• • 1. Mild renal abnormalities, clubfoot, isolated cleft lip/palate, etc. in the fetus are not a reason for exclusion.
• • 2. Isolated 'soft markers' for aneuploidy (such as choroid plexus cysts, echogenic bowel, etc.) are not a reason for exclusion.
• • 3. If a major congenital anomaly is diagnosed \*after\* enrollment, the patient will continue to participate in the study, however, the investigators will plan to analyze the study results with and without these individuals included.
• • 8. Positive aneuploidy screening test (traditional biochemical assay, e.g., quad screen - risk of aneuploidy of 1:25 or higher or cell free deoxynucleic acid (DNA) test result that is screen positive for trisomy 13, trisomy 18, trisomy 21, or sex chromosome abnormality) in the absence of definitive fetal karyotype evaluation.
• • Definitive fetal karyotype evaluation can only be obtained through direct testing of the tissue from the conceptus - by chorionic villus sampling or amniocentesis during pregnancy.
• • The term "suspected aneuploidy" is commonly used in the medical record but this is not a diagnosis and by itself is not informative and not an exclusion criteria.
• • 9. Cystic hygroma or abnormally thickened nuchal translucency ≥ 3 mm at any time in the current gestation, regardless of subsequent diagnostic testing results.
• • Note that a cystic hygroma remains an exclusion criterion regardless of subsequent diagnostic testing results because fetuses with this history carry an elevated risk of major congenital heart disease.
• • Fetal echocardiogram is most accurately performed at 22-24 weeks gestation, which is later than the enrollment gestational age window.
• • 10. Polyhydramnios at or prior to enrollment.
• • o Polyhydramnios is defined as a maximum vertical pocket ≥ 8.0 cm, given that polyhydramnios \<22 weeks has a high likelihood of being associated with congenital anomalies/aneuploidy and/or preterm birth due to preterm prelabor rupture of membranes.
• • 11. For potential participants who meet eligibility criteria ONLY due to prior spontaneous or medically indicated preterm birth: if the prior preterm birth was in a pregnancy complicated by twins, confirmed fetal aneuploidy, or major congenital fetal anomalies in the absence of another pregnancy meeting inclusion criteria they are not eligible.
• • 12. Known HIV positive with viral load greater than 1,000 copies/mL or cluster of differentiation 4 (CD4) count less than 350/mm\^3
• • 13. Unwillingness to undergo randomization.