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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
250
Probiotic
Placebo control
Maternal hemoglobin from complete blood count (CBC) with differential
Venous blood draw
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal iron deficiency anemia (IDA)
Hb \<10.5 g/dL during second trimester and Hb \<11 g/dL during third trimester
Time frame: 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)
Venous blood draw
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal serum ferritin
Venous blood draw
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal serum iron
Venous blood draw
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal sTfR
Venous blood draw
Time frame: 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)
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal hepcidin
Venous blood draw
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal erythropoietin (EPO)
Venous blood draw
Time frame: 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
Time frame: 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
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3), delivery (V4)
Maternal Erythroferrone (ERFE)
Venous blood draw
Time frame: 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
Time frame: delivery
Cord serum ferritin
Cord blood draw
Time frame: delivery
Cord serum iron
Cord blood draw
Time frame: delivery
Cord sTfR
Cord blood draw
Time frame: delivery
Cord total body iron (TBI)
(TBI (mg/kg) = - \[log(TfR/ferritin ratio) - 2.8229\]/0.1207)
Time frame: delivery
Newborn heel stick
Blood spot
Time frame: After delivery before baby released home
Placenta iron transporter (FPN-1 and TFR-1)
Western blot
Time frame: delivery
Placenta iron quantification
Immunohistochemistry
Time frame: delivery
Placenta tissue iron concentration
Inductively coupled plasma-mass spectrometry (ICP-MS)
Time frame: delivery
Fecal abundance of A. muciniphila
Quantitative polymerase chain reaction (qPCR)
Time frame: 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
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)
Microbial mucin degrading enzymes
CaZymes
Time frame: 10-16 weeks GA (V1), 22-28 weeks GA (V2), 30-36 weeks GA (V3)
Stool pH
pH probe
Time frame: 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)
Time frame: delivery
Probiotic acceptance and tolerability
Daily capsule adherence Reported adverse health effects
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
Auditory Brainstem Response (ABR) testing
Interpeak latency I-V
Time frame: -3 days postpartum
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.