Vitamin D Supplementation Among Pregnant Women in Uganda for the Prevention of Hypertensive Disorders in Pregnancy, and Other Adverse Maternal and Foetal Outcomes (MAMA)

Vitamin D Supplementation Among Pregnant Women in Uganda and for the Prevention of Adverse Obstetric Outcomes: a Randomized Controlled Trial

The goal of this randomised controlled trial is to investigate if vitamin D supplementation among pregnant women in Uganda prevents adverse maternal and foetal outcomes, with special emphasis on preeclampsia.

The main question it aims to answer is if Vitamin D supplementation, administered as oral vitamin D₃ at a dose of 2,000 IU once daily, from the time of recruitment to the time of delivery, reduces the incidence of preeclampsia, eclampsia and HELLP syndrome in pregnant women attending ANC at St. Mary's Hospital, Lacor, such incidence being monitored up to six (6) weeks after delivery.

Researchers will compare the effect of oral 2.000 IU vitamin D daily (intervention group) vs. oral placebo daily (control group) on the prevalence of adverse maternal and foetal outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Eclampsia; Preeclampsia; HELLP Syndrome
• Intervention / Treatment: Drug: oral 2.000 IU vitamin D3 (cholecalciferol) daily, in addition to routine ANC supplementations; Other: Placebo

Detailed Description

Introduction:

Vitamin D deficiency is a global health issue, with an estimated prevalence in Africa of about 34%. Black pregnant and breastfeeding women are among the populations with the highest risk of deficiency, with a prevalence of up to 40% in urban Uganda.

Low Vitamin D status in pregnancy seems to be associated with multiple adverse obstetric outcomes, in particular with hypertensive disorders in pregnancy, gestational diabetes, severe postpartum haemorrhage, preterm birth, and low birth weight; these associations have been studied predominantly in Caucasian populations. Recent studies investigated Vitamin D supplementation in preventing preeclampsia, which is known to be more prevalent and severe in dark-skinned women, but results from Africa are scanty; little data have been published on the supplementation of vitamin D in pregnant women in sub-Saharan countries, including Uganda.

Objective: The objective of this trial is to investigate if vitamin D supplementation among pregnant women in Uganda prevents adverse maternal and foetal outcomes, with special emphasis on preeclampsia.

Methods: This will be a double-blinded randomized trial with parallel groups, where pregnant women attending ANC at St. Mary's Hospital, Lacor (Gulu, Northern Uganda), enrolled at gestational age between 13 and 27 weeks, confirmed by ultrasonography at the first antenatal visit, will be invited to participate. Enrolment is planned to start in the last quarter of 2025 and will last approximately 18 months.

Participants will be randomized in a two-armed randomization, with a 1:1 allocation ratio, into:

• Intervention group - 990 women will receive oral 2.000 IU vitamin D daily; or.
• Control group - 990 women will receive an oral placebo daily. A total of 1980 pregnant women will be included; participants will be screened for eligibility at admission and will be required to sign a consent. Questionnaires will be collected upon enrolment, with maternal socio-demographic characteristics and obstetric-medical factors. Study participants will be followed-up throughout the pregnancy, with ANC contacts scheduled at approximately 20, 26, 30, 34, 36, 38, and 40 weeks of gestation, each contact will comprise maternal physical examination, foetal well-being monitoring, the administration of sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy, the supplementation of iron and folic acid, and counselling about birth preparedness, nutrition, and danger signs during pregnancy. Upon delivery, information on maternal and foetal outcomes will be extracted from medical records. Participants will be followed up from delivery to 6 weeks postpartum.

The primary analysis will evaluate the effect of assignment to vitamin D supplementation compared with placebo on the incidence of preeclampsia, eclampsia, or HELLP syndrome, following an intention-to-treat principle. Secondary outcomes will include other adverse maternal outcomes, such as GH, GDM, APH, PPH, PROM and preterm birth, and adverse foetal outcomes, such as growth restriction and low APGAR scores.

Expected results: This study will investigate if the supplementation of Vitamin D in pregnant women in Uganda is effective in preventing preeclampsia, and other adverse foetal and maternal outcomes. The obtained results will pave the way for the recommendation of Vitamin D supplementation during ANC in Uganda, with potentially broad health benefits.

• Study Type: Interventional
• Enrollment (Estimated): 1980
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cristina Reverzani, MBChB, MMED OBGY; Phone Number: +256 760776171; Email: creverzani@libero.it
• Study Contact Backup: Name: Emmanuel Ochola, MBChB, MSc; Phone Number: +256 772561783; Email: ochola.emmanuel@lacorhospital.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Women of age ≥ 18 years, who attend ANC services at St. Mary's Hospital Lacor, satisfying the following criteria:

• with a viable intrauterine pregnancy,
• at gestational age at recruitment between 13 weeks 0 days and 27 weeks 6 days, and
• who consented to participate in the study.

Exclusion Criteria:

• women already on Vitamin D treatment prescribed by a physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention group; Participants will receive oral 2.000 IU vitamin D daily	Drug: oral 2.000 IU vitamin D3 (cholecalciferol) daily, in addition to routine ANC supplementations; The intervention group will comprise pregnant women attending ANC at St. Mary's Hospital, Lacor included in the study, who will be randomized to receive daily oral 2,000 IU Vitamin D3, from the recruitment to the delivery. Eligible participants will be women of age ≥ 18 years, who consented to participate in the study, with a viable intrauterine pregnancy, and at gestational age at recruitment between 13 weeks 0 days and 27 weeks 6 days.
Placebo Comparator: Control group; Participants will receive an oral placebo daily	Other: Placebo; The placebo will be identical to the intervention, with the exception of Vitamin D3, and will have no known pharmacological or physiological activity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome will be the occurrence of maternal preeclampsia, eclampsia and HELLP syndrome.	For each participant, the first occurrence of preeclampsia, eclampsia, or HELLP syndrome during pregnancy will be considered for the primary analysis. The criteria for preeclampsia, eclampsia, or HELLP syndrome are reported in the Operational Definitions of the Study Protocol	From enrolment to 6 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of maternal Gestational Hypertension (GH)	The criteria for GH are defined in the Operational Definitions of the Study Protocol	From enrolment to 6 weeks postpartum
Fatal outcome of delivery (live birth or stillbirth), with APGAR score at 1 and 5 minutes	APGAR score is a widely known and standardized tool to asses the clinical conditions of a new-born immediately after birth, and will be measured at 1 minute and 5 minutes after birth.	At delivery, at 1 minute and 10 minutes after birth
Preterm birth, i.e., Gestational Age at delivery < 37 weeks	Weeks; the determination of the Gestational Age id defined in the Study Protocol	At delivery
Mode of delivery	By vaginal delivery or by Caesarean Section	At delivery
Admission to HDU or ICU		From enrolment to 6 weeks postpartum
New-born birth weight	In Kg	At delivery
Foetal sex and malformations		At delivery
New-born admission to Nursery or Neonatal Intensive Care Unit (NICU)		From delivery to 6 weeks postpartum
The occurrence of maternal Gestational Diabetes (GDM)	The criteria for GDM are defined in the Operational Definitions in the Study Protocol	From enrolment to delivery
The occurrence of maternal Antepartum Haemorrhage (APH)	The criteria for APH are defined in the Operational Definitions of the Study Protocol	From 28 weeks of Gestational Age to delivery
The occurrence of Primary Postpartum Haemorrhage (1.PPH)	The criteria for 1.PPH are defined in the Operational Definitions of the Study Protocol	From delivery to 24 hours post delivery
The occurrence of Prelabour Rupture of Membranes (PROM)	The criteria for PROM are defined in the Operational Definitions of the Study Protocol	From enrolment to delivery

Collaborators and Investigators

• Sponsor: St Mary's Hospital, Lacor
• Collaborators: University of Naples

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 22, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Eclampsia; Pre-Eclampsia; HELLP Syndrome; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Cholecalciferol
• Other Study ID Numbers: MAMA trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No