Iron Deficiency (ID), Pregnancy
Conditions
Brief summary
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.
Interventions
Probiotic
Placebo control
Sponsors
Study design
Eligibility
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maternal hemoglobin from complete blood count (CBC) with differential | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maternal Erythroferrone (ERFE) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Fecal abundance of A. muciniphila | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Quantitative polymerase chain reaction (qPCR) |
| Shot-gun sequencing and analysis (taxonomy and functional profiling) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | MetaPhlAn4 and HUMAnN 2.0 |
| Microbial mucin degrading enzymes | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | CaZymes |
| Stool pH | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | pH probe |
| Adverse pregnancy outcomes post-treatment and at delivery (clinical- EMR) | delivery | Adverse pregnancy outcomes post-treatment and at delivery (clinical-EMR) |
| Probiotic acceptance and tolerability | 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 |
| Auditory Brainstem Response (ABR) testing | -3 days postpartum | Interpeak latency I-V |
| Maternal circulating cytokines (interleukin-6 (IL-6), GM-CS, IL-2, IL-4, IL-8, IL-10, TNFα, and IFNγ | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal serum iron | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal sTfR | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal total body iron (TBI) | 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) |
| Maternal hepcidin | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal erythropoietin (EPO) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal iron deficiency anemia (IDA) | 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 |
| 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) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal serum ferritin | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| Maternal C-reactive protein (CRP) | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4) | Venous blood draw |
| 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) | delivery | Cord blood draw |
| Cord serum ferritin | delivery | Cord blood draw |
| Cord serum iron | delivery | Cord blood draw |
| Cord sTfR | delivery | Cord blood draw |
| Cord total body iron (TBI) | delivery | (TBI (mg/kg) = - \[log(TfR/ferritin ratio) - 2.8229\]/0.1207) |
| Newborn heel stick | After delivery before baby released home | Blood spot |
| Placenta iron transporter (FPN-1 and TFR-1) | delivery | Western blot |
| Placenta iron quantification | delivery | Immunohistochemistry |
| Placenta tissue iron concentration | delivery | Inductively coupled plasma-mass spectrometry (ICP-MS) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Infant characteristics (clinical-EMR) | delivery | Infant sex, weight, gestational age (clinical-EMR) |
| Pre-pregnancy body mass index (BMI) | Up to 6 months before pregnancy | Self-report (confirmed by clinical-EMR, if possible) BMI will be calculated as kg/m2 |
| Gestational weight gain | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | Gestational weight gain |
| Gut microbiome factors | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | Questionnaire related to allergies, diet, travel, and environment |
| Presence of probiotic strain in stool | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | Quantitative polymerase chain reaction (qPCR) |
| Habitual and recent dietary intake | 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 |
| Physical activity | 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3) | Self-report questionnaire |