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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lactiplantibacillus plantarum 299v (LP299V®) | Experimental | Probiotic |
|
| Control | Placebo Comparator | Placebo capsule |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lactiplantibacillus plantarum 299v | Dietary Supplement | Probiotic |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maternal hemoglobin from complete blood count (CBC) with differential | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Measure | Description | Time Frame |
|---|---|---|
| Maternal iron deficiency anemia (IDA) | Hb <10.5 g/dL during second trimester and Hb <11 g/dL during third trimester | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Habitual and recent dietary intake | Food frequency (baseline only) questionnaire and 24-hour diet recall | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Physical activity | Self-report questionnaire |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mary Dawn Koenig, PhD, RN, CNM | Contact | 312-996-7982 | marydh@uic.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois at Chicago | Recruiting | Chicago | Illinois | 60612 | United States |
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| ID | Term |
|---|---|
| D000090463 | Iron Deficiencies |
| ID | Term |
|---|---|
| D019189 | Iron Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Placebo Capsule(s) | Other | Placebo control |
|
Venous blood draw |
| 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal serum ferritin | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal serum iron | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal sTfR | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal total body iron (TBI) | (TBI (mg/kg) = - [log(TfR/ferritin ratio) - 2.8229]/0.1207) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal hepcidin | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal erythropoietin (EPO) | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal circulating cytokines (interleukin-6 (IL-6), GM-CS, IL-2, IL-4, IL-8, IL-10, TNFα, and IFNγ | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal C-reactive protein (CRP) | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Maternal Erythroferrone (ERFE) | Venous blood draw | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| 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) | Cord blood draw | delivery |
| Cord serum ferritin | Cord blood draw | delivery |
| Cord serum iron | Cord blood draw | delivery |
| Cord sTfR | Cord blood draw | delivery |
| Cord total body iron (TBI) | (TBI (mg/kg) = - [log(TfR/ferritin ratio) - 2.8229]/0.1207) | delivery |
| Newborn heel stick | Blood spot | After delivery before baby released home |
| Placenta iron transporter (FPN-1 and TFR-1) | Western blot | delivery |
| Placenta iron quantification | Immunohistochemistry | delivery |
| Placenta tissue iron concentration | Inductively coupled plasma-mass spectrometry (ICP-MS) | delivery |
| Fecal abundance of A. muciniphila | Quantitative polymerase chain reaction (qPCR) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) |
| Shot-gun sequencing and analysis (taxonomy and functional profiling) | MetaPhlAn4 and HUMAnN 2.0 | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Microbial mucin degrading enzymes | CaZymes | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Stool pH | pH probe | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Adverse pregnancy outcomes post-treatment and at delivery (clinical- EMR) | Adverse pregnancy outcomes post-treatment and at delivery (clinical-EMR) | delivery |
| Probiotic acceptance and tolerability | Daily capsule adherence Reported adverse health effects | 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 |
| Auditory Brainstem Response (ABR) testing | Interpeak latency I-V | -3 days postpartum |
| 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Infant characteristics (clinical-EMR) | Infant sex, weight, gestational age (clinical-EMR) | delivery |
| Pre-pregnancy body mass index (BMI) | Self-report (confirmed by clinical-EMR, if possible) BMI will be calculated as kg/m2 | Up to 6 months before pregnancy |
| Gestational weight gain | Gestational weight gain | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Gut microbiome factors | Questionnaire related to allergies, diet, travel, and environment | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |
| Presence of probiotic strain in stool | Quantitative polymerase chain reaction (qPCR) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) |