NCT01542970: PROOM-3

Combined Dietary Supplementation With Lactobacillus Reuteri and Omega-3 PUFA During Pregnancy and Postnatally in Relation to Development of IgE-associated Disease During Infancy

Status unknown NA Last updated 2 March 2012

What this trial tests

NA trial testing Placebo in Allergy in 496 participants. Status unknown.

Timeline

1 February 2012

Primary endpoint
1 June 2017

1 June 2017

Quick facts

Lead sponsor	Ostergotland County Council, Sweden
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	496
Start date	1 February 2012
Primary completion	1 June 2017
Estimated completion	1 June 2017
Sites	1 location across Sweden

Drugs / interventions tested

• Placebo
• Omega-3 fatty acids — full drug profile →
• Refined coconut and peanut oil without L. reuteri
• L. reuteri — full drug profile →

Conditions studied

• Allergy — all drugs for Allergy →
• Gastrointestinal Function — all drugs for Gastrointestinal Function →

Sponsor

Ostergotland County Council, Sweden

Who can join

Adults 18 to 45, female only, with Allergy or Gastrointestinal Function. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• IgE associated disease
  Time frame: 2 years of age
  A food reaction is defined as gastrointestinal symptoms, hives, aggravated eczema or wheezing following ingestion of a certain food with recovery after food elimination from the diet and reoccurrence of symptoms after ingestion of the particular food. Eczema is characterized as reoccurring, itching eczematous and lichenified or nummular dermatitis. Doctor diagnosed wheezing at least three times du

Sponsor's own description

The incidence of allergic disease has increased worldwide during the last decades. Initially, a lot of effort has been put in elucidating which of the known risk factors commonly associated to the development of allergic disease early in life was the cause of this increase. Studies showing a reduced incidence of allergic disease in the former socialist countries in comparison to countries with a "Western lifestyle" have shown that risk factors as allergen exposure, environmental pollution and tobacco exposure are also present in societies with a less affluent lifestyle. This suggests the disappearance of factor protecting against the development of allergic diseases in affluent environment.The development of allergic diseases begins during the first year of life with eczema, both non-IgE- and IgE-associated, and food allergy, progressing during childhood with the development of asthma bronchiale, also both non-IgE- and IgE-associated, and later development of allergic rhinoconjunctivitis, i.e. the atopic march. The immune system of the neonate is influenced by maternal immunity, both via the placenta and breast milk. Thus, the immunological interaction between the mother and her offspring is close during pregnancy and lactation. The association of cord blood IgE levels with maternal but not paternal atopic heredity, may depend on a possibly stronger placental Th2 shift in atopic mothers. Thus, factors influencing/protecting against the development of allergic disease early in life, would be important already during pregnancy, birth and early postnatal life. Two major hypotheses have been assessed during the last decade: Proper microbial stimulation, including the establishment of the gut flora in infancy and the relationship between low omega 3-polyunsaturated fatty acids in the western diet and the incidence of allergic disease.

This is a double blind randomized study. Families with at least one parent/sibling with clinical symptoms/history of allergic disease will be invited to participate in this study. Pregnant mothers will be included in the study at the 20th week of gestation. They will be randomized to 4 study groups, one will receive placebo capsules, the second will receive omega-3 PUFA supplementation and placebo regarding L. reuteri, the third will receive L. reuteri and placebo regarding omega-3 PUFA and the fourth group will receive both omega-3 PUFA and L. reuteri supplementation. Omega-3 supplementation will be given to mothers from pregnancy and lactation while L. reuteri will be given to the mothers during pregnancy and later to the children during the first year of life.The children will be clinically followed by an allergy nurse regularly. Questionnaires regarding data on environment, siblings, pets, breast feeding, smoking exposure, upper respiratory and other infections and clinical symptoms of allergic disease will be filled regularly. Skin prick tests (SPTs) will be performed in the children at 6 and 12 months with milk, egg, wheat, peanut and cat. At 24 months, timothy and birch allergen extracts will be added. A pediatrician will assess the children at 24 months of life and whenever it is needed during the study period. Dietary habits will be assessed during pregnancy (25th gestational week) and 6 months after child birth. Blood samples in the children will be taken from cord blood and at 6, 12 and 24 months of life. Maternal blood samples will be taken at 20th weeks of gestation and at child birth. Milk samples will be collected 1-4 days after partus and monthly during the first 4 months of lactation. Maternal gastrointestinal function will be addressed by validated diary cards. Saliva from the children and fecal samples from mother and child will also be collected according to the following protocol.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood.
   Gunaratne AW, Makrides M, Collins CT. · · 2015 · cited 64× · PMID 26197477 · DOI 10.1002/14651858.cd010085.pub2
2. Effects of vitamin and mineral supplementation during pregnancy on maternal, birth, child health and development outcomes in low- and middle-income countries: A systematic review.
   Keats EC, Oh C, Chau T, Khalifa DS, et al · · 2021 · cited 22× · PMID 37051178 · DOI 10.1002/cl2.1127
3. Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children.
   Ahlberg E, Martí M, Govindaraj D, Severin E, et al · · 2023 · cited 20× · PMID 37102392 · DOI 10.1111/pai.13952
4. Combined prenatal Lactobacillus reuteri and ω-3 supplementation synergistically modulates DNA methylation in neonatal T helper cells.
   Huoman J, Martínez-Enguita D, Olsson E, Ernerudh J, et al · · 2021 · cited 13× · PMID 34193262 · DOI 10.1186/s13148-021-01115-4
5. Changes in peripheral immune populations during pregnancy and modulation by probiotics and ω-3 fatty acids.
   Forsberg A, Abrahamsson TR, Nilsson L, Ernerudh J, et al · · 2020 · cited 12× · PMID 33127947 · DOI 10.1038/s41598-020-75312-1
6. Characterization of Extracellular Vesicles From Fresh vs. Frozen Human Milk Including the Vesicular microRNA Cargo.
   Ahlberg E, Al-Kaabawi A, Eldh M, Gabrielsson S, et al · · 2025 · cited 1× · PMID 41078593 · DOI 10.1002/jex2.70092
7. Effects of pre- and postnatal probiotic and ω-3 fatty acid supplementation on cytokine and chemokine responses to allergens and TLR ligands during infancy.
   Fontes-Oliveira CC, Nylén A, Ljung J, Welin A, et al · · 2026 · PMID 42087191 · DOI 10.1186/s13223-026-01036-y
8. Effects of maternal allergy and supplementation with ω-3 fatty acid and probiotic on human milk oligosaccharides.
   Al-Kaabawi A, Landberg E, Martí M, Severin E, et al · · 2025 · PMID 40747696 · DOI 10.1111/pai.70162