Clinical trial NCT03646487: A Randomized Placebo Controlled Pilot Study of Probiotic Supplementation in At-risk Pregnant Women
Official title: "Pro-Moms" - Mitigating the Effects of Structural Violence on Maternal Iron Status: a Randomized Placebo Controlled Pilot Study of Probiotic Supplementation in At-risk Pregnant Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iron-deficiency
Pregnancy, High Risk
Stress, Psychological
Keywords: pregnancy
iron status
structural violence
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-08-24
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this randomized supplementation feasibility trial is to learn about the feasibility and preliminary efficacy of the probiotic, lactobacillus plantarum 299v (Lp299v), in pregnant individuals at-risk for iron deficiency anemia.

The main questions it aims to answer are:

* Is daily oral Lp299v a feasible and tolerable intervention for pregnant individuals to uptake?
* Does daily oral Lp299v in pregnancy impact maternal and neonatal cord hematological and iron status parameters?

Participants will be randomly assigned to one of two treatment groups: daily intake or probiotic Lp299v + prenatal vitamin with iron or placebo + prenatal vitamin with iron from 15-20 weeks of gestation through delivery.

Researchers will compare the two treatment groups to see if there is a difference in the feasibility of the intervention and the preliminary efficacy on maternal and neonatal cord hematological and iron status parameters.

Detailed description: The most prevalent micronutrient deficiency in the United States (U.S.) is iron; a large majority of cases of iron deficiency (ID) and iron deficiency anemia (IDA) occur among pregnant women. During pregnancy, maternal iron stores are used for the growing fetus, maternal red blood cell (RBC) expansion, and placental growth and development, thus increasing the risk for ID and IDA. Across all trimesters of pregnancy in the U.S., it is estimated that 18% of individuals have ID and 5% have IDA, and within the third trimester, the prevalence of ID exceeds 27%. Prevalence of IDA is even greater among those who identify as Black or low-income. Maternal ID and IDA are associated with increased risk of preterm birth, low infant birth weight, maternal and fetal mortality, and irreversible infant neurocognitive defects. To meet this increasing requirement for iron and to optimize maternal iron nutrition, the Recommended Dietary Allowance for pregnancy is 27 mg/day of iron. However, given the continued high rates of maternal ID and IDA and only modest adherence to daily prenatal vitamins containing iron, alternative approaches to optimizing iron nutrition in pregnancy are needed.

Research has shown that one-time or short-term dosing of the probiotic Lactobacillus plantarum 299v (Lp299v) enhances iron absorption in non-pregnant populations. However, few studies have examined the effect of long-term supplementation on body iron stores. While probiotics are considered safe to consume in pregnancy, only one Lp299v supplementation trial has been conducted during the gestational period to evaluate its effects on maternal iron stores and risk of IDA. This study, among iron-sufficient pregnant Swedish women, showed a significantly lower decline in iron stores and a significantly lower prevalence of IDA in the third trimester among those randomized to Lp299v compared to standard care control.

These results offer potential positive effects for the role of Lp299v in maintaining maternal iron status among those starting pregnancy with sufficient iron stores and who receive care in a decentralized publicly funded healthcare system. However, no studies have evaluated the effect of Lp299v on maternal iron status among individuals at risk for IDA in pregnancy in the U.S., nor have studies extended findings to neonatal iron status. Moreover, it is unknown if positive feasibility and preliminary efficacy would persist in a U.S.-based health care setting with racially, ethnically, and socioeconomically diverse pregnant individuals. Therefore, the objectives of this study were as follows. First and foremost, we examined the feasibility of daily oral Lp299v maternal supplementation taken from the early second trimester through birth. Second, we explored the preliminary efficacy of Lp299v intake on maternal (at-risk for IDA defined as hemoglobin (Hb) between 10.0-12.0 g/dL) and neonatal cord hematological and iron status parameters compared to controls in an urban U.S. academic medical center with a racially, ethnically, and socioeconomically diverse patient population.

Eligibility criteria: Inclusion Criteria:

* a 1st trimester hemoglobin (Hb) of 10.0 - 11.9 g/dl demonstrating ID or risk for prenatal ID
* singleton
* naturally conceived pregnancy
* \< 20 weeks gestation
* 18 - 45 years of age
* sufficient fluency in English to complete study forms
* refrain from non-study dietary and pre-/probiotic supplements while enrolled in the study

Exclusion Criteria:

* oral antibiotic use within the past 2 months
* autoimmune disease
* infection
* receiving steroid treatment
* bariatric surgery
* inflammatory bowel disease
* hyperemesis
* hematologic disorder (e.g., sickle cell disease)
* current tobacco use
* substance abuse in the last 6 months
* other chronic disorders such as type 2 diabetes

Primary outcomes:
measure: Mean Adherence to the Supplement Regimen
timeFrame: 15 weeks gestation through delivery, an average of 25 weeks
Secondary outcomes:
measure: Number of Treatment-emergent Adverse Events Related to GI Symptoms
timeFrame: 15 weeks gestation through delivery, an average of 25 weeks
measure: Maternal Hemoglobin
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal Hematocrit
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal Iron
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal Total Iron Binding Capacity
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal Serum Ferritin
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal Transferrin Saturation
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal High-sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Maternal Iron Deficiency Anemia
timeFrame: Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.
measure: Infant Hemoglobin
timeFrame: delivery
measure: Infant Hematocrit
timeFrame: delivery
measure: Infant Iron
timeFrame: delivery
measure: Infant Total Iron Binding Capacity
timeFrame: delivery
measure: Infant Serum Ferritin
timeFrame: delivery
measure: Infant Transferrin Saturation
timeFrame: delivery
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Mary Dawn D Koenig, PhD, RN, CNM
role: PRINCIPAL_INVESTIGATOR
References:
citation: OjiNjideka Hemphill N, Pezley L, Steffen A, Elam G, Kominiarek MA, Odoms-Young A, Kessee N, Hamm A, Tussing-Humphreys L, Koenig MD. Feasibility Study of Lactobacillus Plantarum 299v Probiotic Supplementation in an Urban Academic Facility among Diverse Pregnant Individuals. Nutrients. 2023 Feb 9;15(4):875. doi: 10.3390/nu15040875.