A Randomized Placebo Controlled Pilot Study of Probiotic Supplementation in At-risk Pregnant Women

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03646487

Enrollment

Registered

2018-08-24

Start date

2018-11-19

Completion date

2020-07-21

Last updated

2023-04-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Iron-deficiency, Pregnancy, High Risk, Stress, Psychological

Keywords

pregnancy, iron status, structural violence

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.

Interventions

DIETARY_SUPPLEMENTProbiotic LP299v 10x10 colony forming units in capsule form

Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form

OTHERPlacebo in capsule form

Daily placebo in capsule form

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 45 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Mean Adherence to the Supplement Regimen	15 weeks gestation through delivery, an average of 25 weeks	Mean adherence to the supplement regimen using Pillsy smart bottles and standard pill counts.

Secondary

Measure	Time frame	Description
Number of Treatment-emergent Adverse Events Related to GI Symptoms	15 weeks gestation through delivery, an average of 25 weeks	Adverse events were captured using the Maternal Adherence Form beginning with the first pill refill visit through delivery. number of participants reporting adverse GI events
Maternal Hemoglobin	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	change in mean maternal serum hemoglobin (g/dl) from baseline to delivery
Maternal Hematocrit	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	Change in mean maternal serum hematocrit (%) from baseline to delivery
Maternal Total Iron Binding Capacity	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	change in mean maternal total iron binding capacity (µmol/L) from baseline to delivery
Maternal Iron	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	change in mean maternal serum iron (µg/dL) from baseline to delivery
Maternal Serum Ferritin	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	change in mean maternal serum ferritin (ng/mL) from baseline to delivery
Maternal Transferrin Saturation	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	change in mean maternal transferrin saturation (%) from baseline to delivery
Maternal High-sensitivity C-reactive Protein (Hs-CRP)	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	change in mean maternal high-sensitivity C-reactive protein (hs-CRP) (mg/L) from baseline to delivery
Maternal Iron Deficiency Anemia	Assessed at baseline (i.e., 15-20 weeks gestation) through delivery; mean change from baseline to delivery is reported.	Number of participants who had iron deficiency anemia (IDA) at delivery. Hemoglobin, obtained from the Complete Blood Count, was used to define trimester-specific maternal IDA, with a downward correction of 0.8 g/dL for Black women. At the time of the study, it was recommended to use a race-adjusted cut-point for IDA. However, this race-adjusted cut-point was recently determined to be unfounded. IDA ranges included hemoglobin ≤11 g/dL for the first trimester, ≤10.5 g/dL for the second trimester, and ≤11 g/dL for the third trimester. IDA ranges with the correction for Black women were hemoglobin ≤10.2 g/dL for the first trimester, ≤9.7 g/dL for the second trimester, and ≤10.2 g/dL for the third trimester.
Infant Hemoglobin	delivery	Mean infant serum hemoglobin (g/dl) from cord blood at delivery.
Infant Hematocrit	delivery	Mean infant serum hematocrit (%) from cord blood at delivery.
Infant Iron	delivery	Mean infant serum iron (µg/dL) from cord blood at delivery.
Infant Total Iron Binding Capacity	delivery	Mean infant total iron binding capacity (µmol/L) from cord blood at delivery.
Infant Serum Ferritin	delivery	Mean infant serum ferritin (ng/mL) from cord blood at delivery.
Infant Transferrin Saturation	delivery	Mean infant transferrin saturation (%) from cord blood at delivery.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Probiotic LP299v Women will receive 1 LP299v (10x10 colony forming units) in capsule form and 1 standard prenatal supplement in tablet form daily beginning at 15 weeks gestation through delivery. Probiotic LP299v 10x10 colony forming units in capsule form: Daily lactobacillus plantarum (LP299v) 10x10 colony forming units in capsule form	12
Placebo Women will receive 1 placebo in capsule form and 1 standard prenatal supplement in table form daily beginning at 15 weeks gestation through delivery. Placebo in capsule form: Daily placebo in capsule form	8
Total	20

Baseline characteristics

Characteristic	Probiotic LP299v	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	12 Participants	8 Participants	20 Participants
Age, Continuous	29.0 years STANDARD_DEVIATION 6.5	28.7 years STANDARD_DEVIATION 6.9	28.9 years STANDARD_DEVIATION 6.5
Education College graduate; graduate school	3 Participants	1 Participants	4 Participants
Education Some high school; some college	9 Participants	7 Participants	16 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	3 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants	5 Participants	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Food iron intake	11.2 mg/1000 kcal	9.8 mg/1000 kcal	10.5 mg/1000 kcal
Gestational age at baseline	12.6 weeks STANDARD_DEVIATION 4.5	13.7 weeks STANDARD_DEVIATION 3.7	13 weeks STANDARD_DEVIATION 4.1
Gestational age at delivery	38.6 weeks STANDARD_DEVIATION 0.7	38.9 weeks STANDARD_DEVIATION 0.7	38.8 weeks STANDARD_DEVIATION 0.7
Health insurance Other	2 Participants	0 Participants	2 Participants
Health insurance Private	6 Participants	1 Participants	7 Participants
Health insurance Public	4 Participants	7 Participants	11 Participants
Household income ≤$30,999	7 Participants	7 Participants	14 Participants
Household income ≥$31,000	5 Participants	1 Participants	6 Participants
Maternal body mass index (BMI) at baseline	31.7 kg/m^2 STANDARD_DEVIATION 6.8	32.9 kg/m^2 STANDARD_DEVIATION 6.8	32.2 kg/m^2 STANDARD_DEVIATION 6.7
Maternal obesity at baseline	8 Participants	4 Participants	12 Participants
Parity 0	5 Participants	3 Participants	8 Participants
Parity 1	3 Participants	3 Participants	6 Participants
Parity 2	4 Participants	2 Participants	6 Participants
Pre-pregnancy body mass index (BMI)	31.1 kg/m^2 STANDARD_DEVIATION 7.3	31.8 kg/m^2 STANDARD_DEVIATION 8.3	31.4 kg/m^2 STANDARD_DEVIATION 7.5
Pre-pregnancy obesity	7 Participants	4 Participants	11 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	10 Participants	5 Participants	15 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	3 Participants	5 Participants
Receiving public assistance SNAP (Supplemental Nutrition Assistance Program)	6 participants	5 participants	11 participants
Receiving public assistance TANF (Temporary Assistance for Needy Families)	1 participants	1 participants	2 participants
Receiving public assistance WIC (Women Infants and Children Program)	3 participants	2 participants	5 participants
Region of Enrollment United States	12 participants	8 participants	20 participants
Relationship status Married	4 Participants	3 Participants	7 Participants
Relationship status Single but living with significant other	3 Participants	3 Participants	6 Participants
Relationship status Single not living with significant other	5 Participants	2 Participants	7 Participants
Sex: Female, Male Female	12 Participants	8 Participants	20 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
Total iron (food and supplement) intake	35.1 mg/1000 kcal	36.8 mg/1000 kcal	36.2 mg/1000 kcal

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 8
other Total, other adverse events	9 / 11	7 / 8
serious Total, serious adverse events	0 / 11	0 / 8

Outcome results

Primary

Mean Adherence to the Supplement Regimen

Mean adherence to the supplement regimen using Pillsy smart bottles and standard pill counts.

Time frame: 15 weeks gestation through delivery, an average of 25 weeks

Population: A total of 20 participants were randomized in the study; n=12 in the Probiotic LP299v group and n=8 in the Placebo group. One participant in the Probiotic LP299v group completed the trial, but was not included in analysis because it was discovered the individual had alpha Thalassemia, a genetic disorder that impacts hemoglobin levels. Therefore, the overall number of participants analyzed in the Probiotic LP299v group was n=11.

Arm	Measure	Value (MEAN)	Dispersion
Probiotic LP299v	Mean Adherence to the Supplement Regimen	67 percentage of adherence	Standard Deviation 29.1
Placebo	Mean Adherence to the Supplement Regimen	80 percentage of adherence	Standard Deviation 25.3

Secondary

Infant Hematocrit

Mean infant serum hematocrit (%) from cord blood at delivery.

Time frame: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Arm	Measure	Value (MEAN)
Probiotic LP299v	Infant Hematocrit	44.3 percentage by volume of red blood cells
Placebo	Infant Hematocrit	49.5 percentage by volume of red blood cells

Secondary

Infant Hemoglobin

Mean infant serum hemoglobin (g/dl) from cord blood at delivery.

Time frame: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Arm	Measure	Value (MEAN)
Probiotic LP299v	Infant Hemoglobin	14.7 g/dl
Placebo	Infant Hemoglobin	16.4 g/dl

Secondary

Infant Iron

Mean infant serum iron (µg/dL) from cord blood at delivery.

Time frame: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Arm	Measure	Value (MEAN)
Probiotic LP299v	Infant Iron	136.2 µg/dL
Placebo	Infant Iron	108.0 µg/dL

Secondary

Infant Serum Ferritin

Mean infant serum ferritin (ng/mL) from cord blood at delivery.

Time frame: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Arm	Measure	Value (MEAN)
Probiotic LP299v	Infant Serum Ferritin	88.8 ng/mL
Placebo	Infant Serum Ferritin	88.0 ng/mL

Secondary

Infant Total Iron Binding Capacity

Mean infant total iron binding capacity (µmol/L) from cord blood at delivery.

Time frame: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Arm	Measure	Value (MEAN)
Probiotic LP299v	Infant Total Iron Binding Capacity	223.6 µmol/L
Placebo	Infant Total Iron Binding Capacity	274.0 µmol/L

Secondary

Infant Transferrin Saturation

Mean infant transferrin saturation (%) from cord blood at delivery.

Time frame: delivery

Population: The neonatal hematological and iron status parameters were examined for the newborns of mothers with ≥80% adherence to the supplement intervention.

Arm	Measure	Value (MEAN)
Probiotic LP299v	Infant Transferrin Saturation	63.8 percentage of saturation
Placebo	Infant Transferrin Saturation	43.3 percentage of saturation

Secondary