Zambian Preterm Birth Prevention Study

Pregnancy Clinical Trial

— ZAPPS  

Official title:

Preventing Preterm Birth in Zambia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02738892
• Other study ID #: 14-2113
• Status: Recruiting
• Start date: August 2015
• Est. completion date: April 2026

Study information

• Verified date: January 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Joan Price, MD, MPH
• Phone: 260 966 668 312
• Email: joan_price[@]med.unc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9000
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Pregnancy
• Premature Birth
• Preterm Birth
• Stillbirth

Locations

Country	Name	City	State
Zambia	Kamwala Health Centre	Lusaka
Zambia	University Teaching Hospital	Lusaka

Sponsors (3)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Bill and Melinda Gates Foundation, Global Alliance to Prevent Prematurity and Stillbirth

Country where clinical trial is conducted

Zambia, 

References & Publications (20)

Aleman A, Cafferata ML, Gibbons L, Althabe F, Ortiz J, Sandoval X, Padilla-Raygoza N, Belizan JM. Use of antenatal corticosteroids for preterm birth in Latin America: providers knowledge, attitudes and practices. Reprod Health. 2013 Jan 29;10:4. doi: 10.1186/1742-4755-10-4. — View Citation

Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012 Jun 9;379(9832):2162-72. doi: 10.1016/S0140-6736(12)60820-4. — View Citation

Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987 Jun;150:782-6. doi: 10.1192/bjp.150.6.782. — View Citation

Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev. 2000;(2):CD000065. doi: 10.1002/14651858.CD000065. — View Citation

Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. doi: 10.1016/S0140-6736(08)60074-4. — View Citation

Gotsch F, Gotsch F, Romero R, Erez O, Vaisbuch E, Kusanovic JP, Mazaki-Tovi S, Kim SK, Hassan S, Yeo L. The preterm parturition syndrome and its implications for understanding the biology, risk assessment, diagnosis, treatment and prevention of preterm birth. J Matern Fetal Neonatal Med. 2009;22 Suppl 2:5-23. doi: 10.1080/14767050902860690. No abstract available. — View Citation

Iams JD. Clinical practice. Prevention of preterm parturition. N Engl J Med. 2014 Jan 16;370(3):254-61. doi: 10.1056/NEJMcp1103640. No abstract available. — View Citation

Kim CJ, Romero R, Kusanovic JP, Yoo W, Dong Z, Topping V, Gotsch F, Yoon BH, Chi JG, Kim JS. The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. Mod Pathol. 2010 Jul;23(7):1000-11. doi: 10.1038/modpathol.2010.73. Epub 2010 Mar 26. — View Citation

Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. doi: 10.1016/S0140-6736(05)71048-5. — View Citation

Lawn JE, Kinney MV, Black RE, Pitt C, Cousens S, Kerber K, Corbett E, Moran AC, Morrissey CS, Oestergaard MZ. Newborn survival: a multi-country analysis of a decade of change. Health Policy Plan. 2012 Jul;27 Suppl 3:iii6-28. doi: 10.1093/heapol/czs053. Erratum In: Health Policy Plan. 2013 Oct;28(7):786-8. — View Citation

Liong S, Di Quinzio MK, Fleming G, Permezel M, Rice GE, Georgiou HM. Prediction of spontaneous preterm labour in at-risk pregnant women. Reproduction. 2013 Aug 21;146(4):335-45. doi: 10.1530/REP-13-0175. Print 2013 Oct. — View Citation

March of Dimes P, Save the Children, WHO. Born Too Soon: The Global Action Report on Preterm Birth. In. Edited by Eds CP Howson MK, JE Lawn. Geneva: World Health Organization; 2012.

Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010 Feb 11;362(6):529-35. doi: 10.1056/NEJMra0904308. No abstract available. — View Citation

Myatt L, Eschenbach DA, Lye SJ, Mesiano S, Murtha AP, Williams SM, Pennell CE; International Preterm Birth Collaborative Pathways and Systems Biology Working Groups. A standardized template for clinical studies in preterm birth. Reprod Sci. 2012 May;19(5):474-82. doi: 10.1177/1933719111426602. Epub 2012 Feb 16. — View Citation

Nour NM. Premature delivery and the millennium development goal. Rev Obstet Gynecol. 2012;5(2):100-5. — View Citation

Oliver RS, Lamont RF. Infection and antibiotics in the aetiology, prediction and prevention of preterm birth. J Obstet Gynaecol. 2013 Nov;33(8):768-75. doi: 10.3109/01443615.2013.842963. — View Citation

Romero R, Espinoza J, Gotsch F, Kusanovic JP, Friel LA, Erez O, Mazaki-Tovi S, Than NG, Hassan S, Tromp G. The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome. BJOG. 2006 Dec;113 Suppl 3(Suppl 3):118-35. doi: 10.1111/j.1471-0528.2006.01150.x. Erratum In: BJOG. 2008 Apr;115(5):674-5. — View Citation

Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, Chaiworapongsa T, Mazor M. The preterm parturition syndrome. BJOG. 2006 Dec;113 Suppl 3(Suppl 3):17-42. doi: 10.1111/j.1471-0528.2006.01120.x. Erratum In: BJOG. 2008 Apr;115(5):674-5. — View Citation

Wang ML, Dorer DJ, Fleming MP, Catlin EA. Clinical outcomes of near-term infants. Pediatrics. 2004 Aug;114(2):372-6. doi: 10.1542/peds.114.2.372. — View Citation

Wisner KL, Parry BL, Piontek CM. Clinical practice. Postpartum depression. N Engl J Med. 2002 Jul 18;347(3):194-9. doi: 10.1056/NEJMcp011542. No abstract available. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm Birth <37	Proportion of deliveries occurring prior to 37 weeks gestation	Measured at delivery
Secondary	Preterm Birth <34	Proportion of deliveries occurring prior to 34 weeks gestation	Measured at delivery
Secondary	Preterm Birth <28	Proportion of deliveries occurring prior to 28 weeks gestation	Measured at delivery
Secondary	Low Birth Weight	Proportion of newborns weighing less than 2500 grams at delivery	Measured at delivery
Secondary	Very Low Birth Weight	Proportion of newborns weighing less than 1500 grams at delivery	Measured at delivery
Secondary	Preterm prelabor rupture of membranes (PPROM)	Proportion of women with PPROM	Enrollment through delivery
Secondary	Spontaneous delivery prior to 37 weeks of gestation	Proportion of spontaneous deliveries	Enrollment through 37 weeks gestation
Secondary	Spontaneous delivery prior to 34 weeks of gestation	Proportion of spontaneous deliveries	Enrollment through 34 weeks gestation
Secondary	Spontaneous delivery prior to 28 weeks of gestation	Proportion of spontaneous deliveries	Enrollment through 28 weeks gestation
Secondary	Birth weight <10th percentile for gestational age	Proportion of newborns with birth weight < 10th percentile for gestational age	Measured at delivery
Secondary	Birth weight <3rd percentile for gestational age	Proportion of newborns with birth weight <3rd percentile for gestational age	Measured at delivery
Secondary	Mother-to-child HIV transmission by 6 weeks postpartum	Proportion of HIV positive newborns	Delivery through 6 weeks postpartum
Secondary	Mother-to-child HIV transmission by 12 months postpartum	Proportion of HIV positive infants	Delivery through 12 months postpartum
Secondary	Maternal mortality	Death of a maternal participant for any reason	Enrollment through 12 months postpartum
Secondary	Fetal, neonatal, and infant mortality	Death of a fetal, neonatal, or infant participant for any reason	Enrollment through 12 months postpartum
Secondary	Infant APGAR scores	APGAR scores at delivery	Measured at delivery

External Links

•   University of North Carolina website