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NCT Number: NCT07076849

Probiotic Supplementation in Optimizing Iron and Hematological Status Among Pregnant Females

Maternal iron deficiency (ID) and iron deficiency anemia (IDA) is associated with maternal and infant mortality, spontaneous preterm birth, maternal postpartum hemorrhage, and neurocognitive defects in the neonate. Therefore, preventing maternal IDA in at-risk women is critical. The standard approach to improving iron status in pregnancy (i.e., oral iron supplements) is suboptimal and gastrointestinal discomforts associated with this approach (i.e., constipation) impairs adherence. The incidence of ID (18%) and IDA (5%) in pregnant populations suggest alternative interventions are needed to optimize iron status in pregnancy. There is increasing evidence that consuming the probiotic Lactoplantibacillus plantarum 299v (LP299V®) can enhance dietary non-heme iron absorption by changes in the composition and metabolic patterns of gut microbiota that reduce intestinal pH, enhance mucin production and favor an anti-inflammatory milieu. This immunomodulatory effect may be important because inflammation stimulates hepatic production of hepcidin, a master regulator of systemic iron homeostasis, which inhibits iron flow into circulation from diet and body stores. Further, the effects of LP299V® may extend to the placenta. The investigators' team showed previously that maternal iron deficiency is associated with changes to placental iron metabolism with more iron sequestered in the placenta and less iron transferring to the fetus. Given its positive effects on maternal iron status, the investigators surmise that LP299V® supplementation will result in higher placenta protein expression of iron transporters, transferrin receptor-1 and ferrroportin-1, and lower placental iron accumulation/content. The primary goal of this study is to test the efficacy of this low-cost, safe, innovative approach to optimizing maternal iron status in individuals at risk for ID in pregnancy [Hb 11.0 - 11.9 g/dL (first trimester) and Hb 10.5 - 11.5 g/dL (second trimester) based on new OB clinical complete blood count (CBC) results obtained from the EHR] from 10-16 weeks gestational age (GA) until the time of labor. The investigators will also test the effects on neonatal (cord blood) iron status and (cord blood + newborn heel stick) Hb at birth and determine the effect of maternal LP299V® supplementation on the maternal gut microbiome, hepcidin-ferroportin axis and placenta iron and placenta transport of iron as its primary mechanisms of action. Finally, the investigators will explore the effect of maternal LP299V® supplementation on infant neurodevelopment at birth. This study is an essential first step toward evaluating if twice daily oral LP299V® is an efficacious, safe, inexpensive, and scalable clinical strategy for the prevention of maternal ID and its related complications in at-risk women.

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Key information

Age range

18 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location status: Recruiting

Location contact

Tory deMartelly, MPH

CONTACT

[email protected]

3123555119

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • singleton naturally conceived pregnancy;
  • at risk of IDA [Hb 11.0 - 11.9 g/dL (first trimester) and Hb 10.5 - 11.5 g/dL (second trimester) based on new OB clinical complete blood count (CBC) results obtained from the EHR;
  • 18 - 45 years old;
  • 10-16 weeks GA;
  • fluency in English to provide consent and complete study procedures;
  • ability to provide consent;
  • and ownership of a smartphone (currently more than 90% of our patient population at the CWH).

Exclusion criteria

  • IDA or other nutritional anemia (i.e., diagnosed or suspected B12 or folate deficiency) based on new OB blood work that includes MCV and MCH to characterize the anemia;
  • recent blood transfusion;
  • autoimmune disorder (e.g., rheumatoid arthritis);
  • inflammatory bowel disease;
  • oral or IV antibiotic use within 2 months;
  • previous spontaneous preterm birth;
  • history of bariatric surgery;
  • malabsorptive disease;
  • current hyperemesis;
  • current eating disorder;
  • hematologic disorder or trait carrier (e.g., hemochromatosis, β-thalassemia);
  • current tobacco, alcohol or illicit drug use (Excluding marijuana).

Treatment and study plan

Lactiplantibacillus plantarum 299v

Dietary Supplement

Probiotic

Placebo Capsule(s)

Other

Placebo control

Primary outcomes

  1. Maternal hemoglobin from complete blood count (CBC) with differential

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

Secondary outcomes

  1. Maternal iron deficiency anemia (IDA)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Hb <10.5 g/dL during second trimester and Hb <11 g/dL during third trimester

  2. Complete blood count (CBC) with differential (WBC, RBC, Hematocrit, MCV, MCH, MCHC, RDW, Platelet Count, MPV and Differential (Absolute and Percent - Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  3. Maternal serum ferritin

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  4. Maternal serum iron

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  5. Maternal sTfR

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  6. Maternal total body iron (TBI)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    (TBI (mg/kg) = - [log(TfR/ferritin ratio) - 2.8229]/0.1207)

  7. Maternal hepcidin

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  8. Maternal erythropoietin (EPO)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  9. Maternal circulating cytokines (interleukin-6 (IL-6), GM-CS, IL-2, IL-4, IL-8, IL-10, TNFα, and IFNγ

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  10. Maternal C-reactive protein (CRP)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  11. Maternal Erythroferrone (ERFE)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Venous blood draw

  12. Maternal Erythroferrone (ERFE) Cord Complete blood count (CBC) with differential (WBC, RBC, Hematocrit, MCV, MCH, MCHC, RDW, Platelet Count, MPV and Differential (Absolute and Percent - Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils)

    Time frame: delivery

    Cord blood draw

  13. Cord serum ferritin

    Time frame: delivery

    Cord blood draw

  14. Cord serum iron

    Time frame: delivery

    Cord blood draw

  15. Cord sTfR

    Time frame: delivery

    Cord blood draw

  16. Cord total body iron (TBI)

    Time frame: delivery

    (TBI (mg/kg) = - [log(TfR/ferritin ratio) - 2.8229]/0.1207)

  17. Newborn heel stick

    Time frame: After delivery before baby released home

    Blood spot

  18. Placenta iron transporter (FPN-1 and TFR-1)

    Time frame: delivery

    Western blot

  19. Placenta iron quantification

    Time frame: delivery

    Immunohistochemistry

  20. Placenta tissue iron concentration

    Time frame: delivery

    Inductively coupled plasma-mass spectrometry (ICP-MS)

  21. Fecal abundance of A. muciniphila

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)

    Quantitative polymerase chain reaction (qPCR)

  22. Shot-gun sequencing and analysis (taxonomy and functional profiling)

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    MetaPhlAn4 and HUMAnN 2.0

  23. Microbial mucin degrading enzymes

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    CaZymes

  24. Stool pH

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    pH probe

  25. Adverse pregnancy outcomes post-treatment and at delivery (clinical- EMR)

    Time frame: delivery

    Adverse pregnancy outcomes post-treatment and at delivery (clinical-EMR)

  26. Probiotic acceptance and tolerability

    Time frame: 10-16 weeks GA, 14-20 weeks GA, 18-24 weeks GA, 22-28 weeks GA, 26-32 weeks GA, 30-36 weeks GA, 34-40 weeks GA, 38-40 weeks GA

    Daily capsule adherence Reported adverse health effects

  27. Auditory Brainstem Response (ABR) testing

    Time frame: -3 days postpartum

    Interpeak latency I-V

Other outcomes

  1. Habitual and recent dietary intake

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    Food frequency (baseline only) questionnaire and 24-hour diet recall

  2. Physical activity

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    Self-report questionnaire

  3. Infant characteristics (clinical-EMR)

    Time frame: delivery

    Infant sex, weight, gestational age (clinical-EMR)

  4. Pre-pregnancy body mass index (BMI)

    Time frame: Up to 6 months before pregnancy

    Self-report (confirmed by clinical-EMR, if possible) BMI will be calculated as kg/m2

  5. Gestational weight gain

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    Gestational weight gain

  6. Gut microbiome factors

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    Questionnaire related to allergies, diet, travel, and environment

  7. Presence of probiotic strain in stool

    Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)

    Quantitative polymerase chain reaction (qPCR)

Study contacts

Contact information is provided by the study sponsor or research team.

Mary Dawn Koenig, PhD, RN, CNM

CONTACT

[email protected]

312-996-7982

Sponsors and collaborators

Lead sponsor

University of Illinois at Chicago

Other

Registry information

Official study title

Mechanistic Pathways of Probiotic Supplementation in Optimizing Iron and Hematological Status Among Pregnant Females at Risk of Iron Deficiency Anemia

Acronym: ProMoms

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Jul 22, 2025
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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