Effect of Probiotics Consumed During Pregnancy on the Incidence of Mastitis

Multicenter, Randomized, Double-blind, Controlled Parallel Nutritional Intervention Study to Evaluate the Effect of Consumption During Pregnancy and the Lactation Period of Lactobacillus Fermentum CECT5716 on the Incidence of Mastitis

The aim of the present study is to evaluate the effect of consumption during pregnancy and the lactation period of the probiotic L. fermentum CECT5716 on the incidence of mastitis.

Bacterial load and immunological parameters in breast milk, parameters related to breastfeeding as well as health parameters of the mother and baby will also be evaluated.

Study Overview

• Status: Completed
• Conditions: Women's Health; Lactation; Mastitis; Breast Milk; Infant Health
• Intervention / Treatment: Dietary supplement: Lactobacillus fermentum CECT5716; Dietary supplement: Maltodextrin

Detailed Description

Pregnancy and lactation are important moments for the child that will determine their development and future health. One of the key processes is when the microbiota is established in the baby. Contamination during delivery with the mother's vaginal flora, as well as bacteria from the microbiota of breast milk, are important sources for intestinal colonization. However, the mother's microbiota can suffer alterations that affect the health of the mother and can also have an effect on the baby.

Mastitis is a condition of the mammary gland that can affect between 3-30% of women during the period of lactation and is the first cause of abandonment of it. It is associated with a dysbiosis with the proliferation of microorganisms in milk such as Staphylococcus and Streptococcus.

Previous studies carried out with the strain L. fermentum CECT5716 have demonstrated a powerful regulating activity of the microbiota of breast milk that translates into a preventive and curative effect on mastitis. The highest incidence of mastitis occurs during the first weeks after delivery, so the investigator's working hypothesis is that the modulation of the maternal microbiota before delivery would improve the effectiveness of the probiotic strain consumption.

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Granada, Spain, 18014
    • Hospital Virgen de las Nieves
  • Andalucia
    • Marbella, Andalucia, Spain, 29603
      • Hospital Costa del Sol
  • Grabada
    • Granada, Grabada, Spain, 18007
      • Hospital Campus de la Salud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Normal development of pregnancy
• Single fetus pregnancy
• Be in week 28-32 of pregnancy
• Intention to breastfeed the child for 16 weeks

Exclusion Criteria:

• Having a breast disease that hinders or prevents breastfeeding
• Have been taking probiotic supplements 2 weeks before starting the study
• Have a low expectation of adherence to the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L. fermentum CECT5716 3x109 ufc; Volunteers will take 1 capsule per day with L. fermentum CECT5716 3x109 cfu mixed with maltodextrin from week 28-32 of gestation up to 16 weeks after delivery.	Dietary supplement: Lactobacillus fermentum CECT5716; Each participant will consume 1 capsule per day in one of the main meals without any restriction in the diet or in their life habits.
Placebo Comparator: Maltodextrin; Volunteers will take 1 capsule per day with maltodextrin from week 28-32 of gestation up to 16 weeks after delivery.	Dietary supplement: Maltodextrin; Each participant will consume 1 capsule per day in one of the main meals without any restriction in the diet or in their life habits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of mastitis	Total events during breastfeeding period /total number of participants	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota of breast milk	Load of Staphylococcus, S. aureus, S. epidermidis, Streptococcus, Lactobacillus and L. fermentum CECT5716 in breast milk	4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of mastitis	Reappearance of mastitis symptoms	4 months
Breast pain questionnaire	Mcgill Pain Questionnaire, validated for Spain. The Questionnaire has four dimensions or scales of measures of intensity: Sensory Intensity Value, Affective Intensity Value, Current Intensity Value, and Evaluative Intensity Value. The scales of the Questionnaire were calculated as the sum of their items. Those items were re-corded as 1 if the participant described the pain or as 0 if the participant did not report that type of pain. Thus, the sensory intensity scale can range from 0 to 33, as the full scale is formed by 33 items. The Affective scale varies from 0 to 19, and the scales of Current Intensity and Evaluative Intensity can range from 0 to 6 and 5, respectively	4 months
Time of Breastfeeding	Date of initiation and cessation of breastfeeding	4 months
Percentage of infants breastfeed	Percentage of infants who receive exclusive breastfeeding	4 months
Measurement of biomarkers of inflammation in breast milk	Concentration of IL-1b, IL-6, IL-8, IL-17, TNF-α in breast milk	4 months
Immunoglobulins in breast milk	Concentration of IgA, IgG1, IgG2, IgG3, IgG4 and IgM in breast milk	4 months
Minerals in breast milk	Concentration of calcium (μg/L), magnesium (μg/L) and potassium (μg/L) in breast milk	4 months
Baby feces microbiota	Presence of Escherichia coli, Clostridium, Bacteroides, Bifidobacteria, Lactobacillus and L. fermentum CECT5716 in baby feces	4 months
Data on childbirth	Incidence of cesareans and incidence of antibiotic use during delivery.	4 months
Baby's anthropometric measures	Anthropometric measures of the baby (weight in kg, height in cm and BMI in kg/m2) at birth, 4 weeks, 8 weeks and 16 weeks.	16 weeks
Data about the intestinal health of the baby	Data about stool frequency, colour and consistency of the feces and gasses	4 months
Data about sleep parameters of the baby	Hours of night sleeping per day and hours of total sleeping during the day	4 months

Collaborators and Investigators

• Sponsor: Biosearch S.A.
• Investigators: Principal Investigator: Nicolás Mendoza, MD, PhD, Professor of Gynecology at the Faculty of Medicine of the University of Granada

Publications and helpful links

General Publications

• Crepinsek MA, Taylor EA, Michener K, Stewart F. Interventions for preventing mastitis after childbirth. Cochrane Database Syst Rev. 2020 Sep 29;9(9):CD007239. doi: 10.1002/14651858.CD007239.pub4.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Probiotics; Lactation; Mastitis; Gestation
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Skin Diseases; Breast Diseases; Puerperal Disorders; Mastitis
• Other Study ID Numbers: P045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No