Pilot Study of Prenatal Choline Supplementation

A Randomized, Double-Blind, Placebo-controlled Clinical Trial of Choline Supplementation During Pregnancy to Mitigate Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Development: Pilot Arm for Non-Drinking Women

A double-blind, randomized, placebo-controlled trial (RCT; NCT04395196) of prenatal choline supplementation is ongoing (1) to assess the effectiveness of maternal choline supplementation during pregnancy to mitigate effects of PAE on three primary outcomes: infant recognition memory and postnatal growth restriction (weight and head circumference); (2) to assess the efficacy of this supplementation for mitigating alcohol effects on the following secondary outcomes: infant eyeblink conditioning, postnatal length, and information processing speed. The study design was based on a pilot feasibility study in 70 heavy-drinking pregnant women. Infants in the choline-treated arm were more likely to meet criterion for eyeblink conditioning than those in the placebo arm. Infants born to both the choline- and placebo-treated mothers were small at birth, but those in the choline arm showed considerable catch-up growth in weight and head circumference by 6.5 months, which persisted through 12 months. At 12 months, infants in the choline arm showed markedly better recognition memory compared to placebo-treated on the Fagan Test of Infant Intelligence, which is known to have predictive validity for school-age IQ. Of note, infants with heavy prenatal alcohol exposure whose mothers were in the active choline treatment arm performed better on FTII novelty preference neurobehavioral testing than infants in an observational study that was running in parallel who had no prenatal alcohol exposure. These pilot findings indicate that any beneficial effects of prenatal choline supplementation seen may be due in part or entirely due to general beneficial effects on fetal brain development rather than mechanisms that are specific to the teratogenic effects of alcohol. Thus, the aim of this pilot study is to enroll and randomize 50 alcohol-abstaining pregnant women to participate in an identical study protocol (same study procedures and primary and secondary outcomes) to NCT04395196, which includes only alcohol-consuming pregnant women. Effect sizes between this pilot, non-drinking group and the larger study of alcohol-consuming women will be compared to explore the degree to which prenatal choline supplementation benefits growth and neurobehavior in infants without prenatal alcohol exposure and to explore the degree to which beneficial treatment effects of choline are specific to prenatal alcohol exposure.

Study Overview

• Status: Recruiting
• Conditions: Brain Development; Choline Nutrition
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Choline bitartrate

Detailed Description

The study protocol will be identical to NCT04395196 except for sample size (goal = 50 pregnant women and their infants) and that instead of including heavy-drinking pregnant women, inclusion criteria require that women have fully abstained from alcohol during pregnancy at the time of randomization. All other inclusion/exclusion criteria and study procedures are identical.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sandra W Jacobson, PhD; Phone Number: +13139935454; Email: sandra.jacobson@wayne.edu
• Study Contact Backup: Name: R. Colin Carter, MD, MMSc; Phone Number: +12123052995; Email: rcc2142@cumc.columbia.edu

Study Locations

• South Africa
  • Cape Town, South Africa
    • Recruiting
    • University of Cape Town
    • Contact: Anthea Van Wyk; Phone Number: +27665643491; Email: uctmoms@gmail.com
    • Contact: Ernesta M Meinjtes, PhD; Email: ernesta.meintjes@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥18 yr
• ≤20 wk gestation
• Singleton pregnancy
• Abstinence from alcohol since conception (by report)
• Current choline dietary intake <1 g/day
• Language fluency in English or Afrikaans

Exclusion Criteria:

• Use of methamphetamine or other illicit drugs other than marijuana during the past year
• HIV positive
• Pharmacologic treatment for a serious pre-existing medical condition (e.g., diabetes, hypertension, epilepsy, or cardiac problems)
• Having another child enrolled in the trial from a previous pregnancy
• Plans for mother or child to move away from the area prior to study completion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo identical to active treatment in appearance, taste, and smell.	Dietary supplement: Placebo; Provided in beverage form
Experimental: High-dose choline supplementation; 2 g choline cation per day	Dietary supplement: Choline bitartrate; Provided in beverage form.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant recognition memory	Novelty preference from the Fagan Test of Infant Intelligence	12 months
Postnatal infant weight gain		6.5 months
Postnatal growth in infant head circumference		6.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant information processing speed	Processing speed on the Fagan Test of Infant Intelligence	12 months
Postnatal growth in infant length		6.5 months

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: Columbia University; University of Cape Town
• Investigators: Principal Investigator: Sandra W Jacobson, PhD, Wayne State University; Principal Investigator: Joseph L Jacobson, PhD, Wayne State University; Principal Investigator: R. Colin Carter, MD, MMSc, Columbia University; Principal Investigator: Ernesta M Meinjtes, PhD, University of Cape Town

Study record dates

Study Major Dates

• Study Start (Estimated): July 8, 2026
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): May 15, 2028

Study Registration Dates

• First Submitted: July 6, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 11, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: dietary supplementation; Choline; Prenatal nutrition
• Additional Relevant MeSH Terms: Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Quaternary Ammonium Compounds; Onium Compounds; Trimethyl Ammonium Compounds; Choline
• Other Study ID Numbers: UCTCHOLINERCTPHASEB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share deidentified data with researchers and regulatory bodies who request the data for verification of findings, for collaboration, and/or for research purposes deemed ethical and scientifically justified by the PIs.
• IPD Sharing Time Frame: We will share data as described above after publication of the main findings.
• IPD Sharing Access Criteria: Requests should be made to the principle investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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