Clinical trial NCT02738892: Zambian Preterm Birth Prevention Study
Official title: Preventing Preterm Birth in Zambia
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Pregnancy
Stillbirth
Preterm Birth
Keywords: Pregnancy
Stillbirth
Preterm birth
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Global Alliance to Prevent Prematurity and Stillbirth
name: Bill and Melinda Gates Foundation
First posted: 2016-04-14
Enrollment: 9000
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be conducted at Kamwala Health Centre and the University Teaching Hospital, both in Lusaka, Zambia.

Brief summary: This prospective non-intervention cohort study will enroll women in the first or early second trimester of pregnancy and follow them through delivery (or end of pregnancy) and 1 year postpartum.

Infants will also be followed until 1 year postpartum. Detailed medical and obstetrical information will be collected, as well as biological samples, in order to better elucidate the biological mechanisms leading to preterm delivery among Zambian women, in an effort to identify new strategies for prevention.

Detailed description: After consenting to study participation, women will be asked their detailed medical and obstetrical history. Participants will be provided standard of care. Blood, urine, and vaginal specimens will also be collected for the biorepository from those who consent to participate. Participants will also be screened for depression using the Edinburgh Postnatal Depression Scale (EPDS).

Throughout the study, participants will receive education about nutrition, pregnancy health, and the signs and symptoms of complications of pregnancy, including preterm labor and preterm premature rupture of membranes. Study visits for will be scheduled at 24, 28, 32, and 36 weeks gestation, at the time of discharge from the labor and delivery ward if possible, and at 7 days, 28 days, 42 days, 6 months, and 12 months postpartum

During each study visit (i.e., at 24, 32, and 36 weeks gestation), participants will receive the routinely recommended screening and treatment. This will consist of weight, blood pressure, and symptom screening, as well as measurements of fetal growth (fundal height) and fetal well being (fetal heart rate) at each visit. Screening and treatment of common pregnancy complications will also be provided if clinically indicated. All participants will undergo maternal hemoglobin testing and urinalysis at the 24 and 32-week visits. Maternal random fasting glucose testing will be conducted at the 28-week visit to screen for gestational diabetes. Syphilis titers will be obtained at a minimum at the 36 week visit for participants seropositive at screening to monitor serologic response after treatment. HIV testing will be repeated at 28 weeks for participants uninfected at screening, and HIV Viral Load and T cell assays will be performed at the 28- and 36-week visits for any seroconverters. Participants who are HIV-infected at screening will undergo HIV Viral Load and T cell assays at 28 and 36 weeks. At 24, 28, and 36 weeks, blood, urine, oropharyngeal, and vaginal swabs will be collected. We will also collect a rectal swab at the 36-week visit. .

At the time of delivery, the study team will obtain detailed information about the clinical management of the participant's delivery, as well as the delivery outcome for both the mother and her infant(s). A urinalysis, complete blood count with differential, blood chemistry testing will be performed. We will also obtain information on interval complications and mortality. In addition, we will collect samples of the placenta, umbilical cord, and cord blood after delivery for various assessments. 4-5 drops of cord blood will be applied to designated filter paper within pre-printed circles. Newborn heel-prick samples will be collected 24-72 hours after birth or sooner if the newborn is discharged from hospital within 24 hours of delivery.

There will be four study visits during the postnatal period, at 7 days, 42 days, 6 months, and 12 months postpartum. At these visits, we will assess interval maternal or infant complications and/or mortality and measure anthropometrics. Once again, participants will receive routinely recommended screening and treatment.

Maternal hemoglobin will be measured at all post-partum visits. Urinalysis will be performed at the 42-day visit only. Maternal blood, urine, oral/pharyngeal and vaginal specimens will be collected for storage and protocol related testing at the 42-day visit. Maternal syphilis and HIV testing will be repeated at the 42-day, 6- and 12-month visits for participants who are uninfected. HIV-exposed infants will have blood collected for early infant diagnosis at the 42-day and 6- and 12-month visits; this will be done via heel prick and dried blood spot (DBS) cards requiring five drops of blood. Maternal participants will again be screened for depression using the EPDS

Eligibility criteria: Inclusion Criteria:

Pregnant women ≥15 years will be eligible to participate. Additionally, participants will:

1. Have a completed screening ultrasound with gestational age \< 20 weeks
2. Be HIV-uninfected at enrollment (NB: prior to Protocol Version 4.0 \[3 Nov 2017\] enrolled both HIV-infected and uninfected women)
3. Have a singleton or twin pregnancy with fetal heart tones confirmed by ultrasound
4. Reside within Lusaka with no plans to relocate during the study follow-up period
5. Be willing to provide written, informed consent
6. Be willing to allow their infants to participate in the study

Exclusion criteria:

1. Pregnant women \> 24 weeks' gestation or with screening ultrasound ≥ 16 weeks
2. Infants born to women not enrolled in the study

Primary outcomes:
measure: Preterm Birth <37
timeFrame: Measured at delivery
Secondary outcomes:
measure: Preterm Birth <34
timeFrame: Measured at delivery
measure: Preterm Birth <28
timeFrame: Measured at delivery
measure: Low Birth Weight
timeFrame: Measured at delivery
measure: Very Low Birth Weight
timeFrame: Measured at delivery
measure: Preterm prelabor rupture of membranes (PPROM)
timeFrame: Enrollment through delivery
measure: Spontaneous delivery prior to 37 weeks of gestation
timeFrame: Enrollment through 37 weeks gestation
measure: Spontaneous delivery prior to 34 weeks of gestation
timeFrame: Enrollment through 34 weeks gestation
measure: Spontaneous delivery prior to 28 weeks of gestation
timeFrame: Enrollment through 28 weeks gestation
measure: Birth weight <10th percentile for gestational age
timeFrame: Measured at delivery
measure: Birth weight <3rd percentile for gestational age
timeFrame: Measured at delivery
measure: Mother-to-child HIV transmission by 6 weeks postpartum
timeFrame: Delivery through 6 weeks postpartum
measure: Mother-to-child HIV transmission by 12 months postpartum
timeFrame: Delivery through 12 months postpartum
measure: Maternal mortality
timeFrame: Enrollment through 12 months postpartum
measure: Fetal, neonatal, and infant mortality
timeFrame: Enrollment through 12 months postpartum
measure: Infant APGAR scores
timeFrame: Measured at delivery
Other outcomes:
Locations:
city: Lusaka
country: Zambia
facility: Kamwala Health Centre
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Jeff Stringer, MD
role: PRINCIPAL_INVESTIGATOR
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