Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight (NAMI)

• ClinicalTrials.gov Identifier: NCT00167700
• Recruitment Status: Unknown
• First Posted: September 14, 2005
• Last Update Posted: October 4, 2012
• Sponsor: University of Turku
• Collaborator: Academy of Finland
• Information provided by: University of Turku

Study Description

Brief Summary:

Combined programme: Nutrition, Allergy, Mucosal immunology and Intestinal microbiota (NAMI) was created with the objective to reverse the rising trend of chronic inflammatory diseases, such as allergic disease and obesity, by control of the internal and external environments of the infant. To approach this problem, the project aims to characterize

• how immunology is regulated during pregnancy and early infancy,
• how the immune interaction between mother and child is influenced by nutritional and microbial factors, and
• how the regulation is related to disease risk.

Condition or disease	Intervention/treatment	Phase
Allergic Disease; Obesity; Immunology	Behavioral: Dietary counselling and placebo; Behavioral: Dietary counselling and probiotics; Dietary Supplement: Placebo capsules; Dietary Supplement: Probiotics; Dietary Supplement: Prebiotics	Not Applicable

Detailed Description:

While allergic diseases comprise the most common chronic disease in childhood, obesity is the most prevalent nutritional disorder among children throughout the world. In Europe, an estimated 20% of children and adolescents are overweight with one-third of these being considered obese. Moreover, escalation of these problems is expected in the future, since the velocity of propagation is highest in children. Although genetic factors can determine the propensity of an individual to become allergic or obese, these unlikely explain the recent and progressive worldwide increases in incidence. Rather, it would appear that the environmental changes more directly shape the risk during a critical period of life when the scene is set for the consolidation of the immune responder type. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, heritable changes in gene expression occurring without alterations in the DNA sequences.

Specifically current research interest is directed towards health promotion and reducing the risk of disease evaluating the probiotic effects with specific foods and nutrients, and assessing their interactions in optimal combination and food matrix. For this purpose a series of interventions studies evaluate the both the optimal timing of probiotic intervention and the optimal mode of administration.

Sections:

Prenatal

RCT 2 Randomized, parallel-design clinical trial of 3 groups. Pregnant women (n=256) from families with at least one member having an allergic disease have been recruited from maternal welfare clinics and randomly assigned to control group or one of the intervention groups. Mothers in the dietary intervention groups received dietary counselling with specific attention to the quality and quantity of fat in the diet. To promote the achievement of current dietary recommendations, mothers have been provided with foods which have a favourable fat composition (e.g. spreads). The subjects in the intervention groups have been further randomized (double-blind randomization) to receive either placebo or a probiotic preparation, 1010 cfu of both Lactobacillus rhamnosus GG and Bifidobacterium lactis and controls received placebo in a single-blind manner. Dietary food products and probiotic supplementation have been continued from the 1st trimester of pregnancy until the end of exclusive breast feeding, maximum of 6 months.

Perinatal

RCT 1 Randomized double-blind, placebo-controlled study of 2 groups. Pregnant women (n=159) have been randomized into one of the study groups 2-4 weeks before term to receive placebo (microcrystalline cellulose) or probiotic Lactobacillus rhamnosus GG (ATCC 53103; 1010 cfu). After delivery probiotics/ placebo were administered orally to the infants for 6 months. General information to prevent allergy has been given in written form to all: to breast-feed for at least 4-6 months; to begin solid foods at 4-6 months; no smoking by caretakers.

RCT 3 Randomized double-blind, placebo-controlled clinical trial of 3 groups. Pregnant women (n=241) with a history of atopic diseases have been assigned to one of the treatment groups: to receive for 2 months before delivery and for 2 months thereafter, when they are breast-feeding, either placebo or Lactobacillus rhamnosus and Bifidobacterium longum or Lactobacillus paracasei and Bifidobacterium longum.

Postnatal

RCT 4 Randomized double-blind, placebo-controlled study of 3 groups. Neonates (n=94) fulfilling the following criteria: gestational age at birth between 32nd and 36th weeks, weight over 1500 g and no congenital defects of gastrointestinal system or other defects that prevent enteral nutrition, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) or a prebiotic preparation (a mixture of Polydextrose and Galacto-oligosaccharideOS in a 1:1 ratio). The treatment continues for 2 months.

RCT 5 Randomized double-blind, placebo-controlled clinical trial of 2 groups. 2-6 weeks old formula- and breast-fed colic infants (n=30), who cry without medical cause for 3h/d, for 3days/week, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) for 4 weeks. Formula-fed infants receive extensively hydrolysed formula and mothers of breast-fed infants avoid cow's milk in their diet.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota (NAMI): Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight
• Study Start Date: February 1997
• Estimated Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Probiotics	Dietary Supplement: Probiotics
Experimental: Probiotics + Dietary counseling	Behavioral: Dietary counselling and probiotics; Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Probiotics
Experimental: Dietary counseling + placebo	Behavioral: Dietary counselling and placebo; Counseling to conform with the dietary recommendations. Food products commercially available including spreads and salad dressing. Placebo capsules.
Experimental: Prebiotics	Dietary Supplement: Prebiotics
Placebo Comparator: Placebo	Dietary Supplement: Placebo capsules; Placebo capsules
No Intervention: Control

Outcome Measures

Primary Outcome Measures :

1. Number of participants with allergic disease [ Time Frame: Up to 13 years ]
2. Weight gain [ Time Frame: Up to 13 years ]
3. Number of patients with chronic inflammatory disease [ Time Frame: Up to 13 years ]

Secondary Outcome Measures :

1. Innate immune gene expression patterns [ Time Frame: Up to 13 years ]
2. Microbiota composition
   Amount of bacterial cells (per gram of faeces of mothers and infants as well as of breast milk) is measured using multiple methods, i.e. pyrosequencing, HIT-CHIP, qPCR, FISH and DGGE.
3. Plasma glucose [ Time Frame: Up to 13 years ]
4. Cytokines in peripheral blood [ Time Frame: Up to 13 years ]
5. Cytokine profile in breast milk [ Time Frame: Up to 13 years ]
6. Cytokine profile in peripheral blood mononuclear cells (PBMC) [ Time Frame: Up to 13 years ]
7. GHbA1c [ Time Frame: Up to 13 years ]
8. Fatty acids [ Time Frame: Up to 13 years ]
9. Lipoproteins [ Time Frame: Up to 13 years ]
10. Intakes of foods and nutrients [ Time Frame: Up to 13 years ]
11. Blood pressure [ Time Frame: Up to 13 years ]
12. Leukotrienes in peripheral blood [ Time Frame: Up to 13 years ]
13. Adipokines [ Time Frame: Up to 13 years ]
14. Amount of crying in minutes [ Time Frame: Up to 1 year ]
    Crying minutes per day
15. Number of patients with functional gastrointestinal disorders [ Time Frame: Up to 13 years ]
16. Incidence of viral infections [ Time Frame: Up to 13 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Pregnant women from families with at least one family member having an allergic disease

Exclusion Criteria:

• Women presenting severe immunological or other chronic diseases (rheumatoid arthritis, diabetes, inflammatory bowel disease, thyroid diseases, malignancies etc.)
• Women who cannot be expected to comply with treatment
• Women currently participating or having participated in other clinical trial during the last 2 months prior to the beginning of the intervention.

Contacts and Locations

Contacts

Contact: Johanna Hvitfelt-Koskelainen, RN; +358 2 313 0000 ext 1463; Johanna.Hvitfelt-Koskelainen@tyks.fi

Locations

Finland

Turku University Central Hospital; Recruiting

Turku, Finland, 20520

Contact: Erika Isolauri, MD, PhD +358 2 313 0000 ext 2433 erika.isolauri@utu.fi

Principal Investigator: Erika Isolauri, MD, PhD

Principal Investigator: Seppo Salminen, PhD

Principal Investigator: Kirsi Laitinen, PhD

Sub-Investigator: Marko Kalliomäki, MD, PhD

Sub-Investigator: Samuli Rautava, MD, PhD

Sub-Investigator: Minna-Maija Grönlund, MD, PhD

Sub-Investigator: Merja Nermes, MD, PhD

Sub-Investigator: Maria Carmen Collado, PhD

Sub-Investigator: Ulla Hoppu, PhD

Sub-Investigator: Raakel Luoto, MD, PhD

Sub-Investigator: Jonna Normia, MD, PhD

Sponsors and Collaborators

University of Turku

Academy of Finland

Investigators

• Study Director: Erika Isolauri, MD, PhD; University of Turku

More Information

Publications of Results:

Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001 Apr 7;357(9262):1076-9. doi: 10.1016/S0140-6736(00)04259-8.

Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003 May 31;361(9372):1869-71. doi: 10.1016/S0140-6736(03)13490-3.

Laiho K, Lampi AM, Hamalainen M, Moilanen E, Piironen V, Arvola T, Syrjanen S, Isolauri E. Breast milk fatty acids, eicosanoids, and cytokines in mothers with and without allergic disease. Pediatr Res. 2003 Apr;53(4):642-7. doi: 10.1203/01.PDR.0000055778.58807.C8. Epub 2003 Jan 29.

Laitinen K, Kalliomaki M, Poussa T, Lagstrom H, Isolauri E. Evaluation of diet and growth in children with and without atopic eczema: follow-up study from birth to 4 years. Br J Nutr. 2005 Oct;94(4):565-74. doi: 10.1079/bjn20051503.

Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. 2012 Jul;72(1):77-85. doi: 10.1038/pr.2012.42. Epub 2012 Mar 27.

Laitinen K, Poussa T, Isolauri E; Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota Group. Probiotics and dietary counselling contribute to glucose regulation during and after pregnancy: a randomised controlled trial. Br J Nutr. 2009 Jun;101(11):1679-87. doi: 10.1017/S0007114508111461. Epub 2008 Nov 19.

Hoppu U, Isolauri E, Laakso P, Matomaki J, Laitinen K. Probiotics and dietary counselling targeting maternal dietary fat intake modifies breast milk fatty acids and cytokines. Eur J Nutr. 2012 Mar;51(2):211-9. doi: 10.1007/s00394-011-0209-0. Epub 2011 May 31.

Niinivirta K, Isolauri E, Laakso P, Linderborg K, Laitinen K. Dietary counseling to improve fat quality during pregnancy alters maternal fat intake and infant essential fatty acid status. J Nutr. 2011 Jul;141(7):1281-5. doi: 10.3945/jn.110.137083. Epub 2011 May 18.

Ilmonen J, Isolauri E, Poussa T, Laitinen K. Impact of dietary counselling and probiotic intervention on maternal anthropometric measurements during and after pregnancy: a randomized placebo-controlled trial. Clin Nutr. 2011 Apr;30(2):156-64. doi: 10.1016/j.clnu.2010.09.009.

Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: a prospective, randomized, placebo-controlled study. Early Hum Dev. 2012 Jun;88(6):339-44. doi: 10.1016/j.earlhumdev.2011.09.006. Epub 2011 Sep 25.

Ojala T, Aaltonen J, Siira S, Jalonen J, Ekholm E, Ekblad U, Laitinen K. Fetal cardiac sympathetic activation is linked with maternal body mass index. Early Hum Dev. 2009 Sep;85(9):557-60. doi: 10.1016/j.earlhumdev.2009.05.009. Epub 2009 Jun 12.

Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr. 2010 Jun;103(12):1792-9. doi: 10.1017/S0007114509993898. Epub 2010 Feb 4.

Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010 Nov;92(5):1023-30. doi: 10.3945/ajcn.2010.29877. Epub 2010 Sep 15.

Aaltonen J, Ojala T, Laitinen K, Poussa T, Ozanne S, Isolauri E. Impact of maternal diet during pregnancy and breastfeeding on infant metabolic programming: a prospective randomized controlled study. Eur J Clin Nutr. 2011 Jan;65(1):10-9. doi: 10.1038/ejcn.2010.225. Epub 2010 Oct 13.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Davidson SJ, Barrett HL, Price SA, Callaway LK, Dekker Nitert M. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2021 Apr 19;4(4):CD009951. doi: 10.1002/14651858.CD009951.pub3.

Partty A, Kalliomaki M, Salminen S, Isolauri E. Infantile Colic Is Associated With Low-grade Systemic Inflammation. J Pediatr Gastroenterol Nutr. 2017 May;64(5):691-695. doi: 10.1097/MPG.0000000000001340.

Partty A, Lehtonen L, Kalliomaki M, Salminen S, Isolauri E. Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial. Pediatr Res. 2015 Oct;78(4):470-5. doi: 10.1038/pr.2015.127. Epub 2015 Jul 7.

Luoto R, Ruuskanen O, Waris M, Kalliomaki M, Salminen S, Isolauri E. Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2014 Feb;133(2):405-13. doi: 10.1016/j.jaci.2013.08.020. Epub 2013 Oct 13.

Partty A, Luoto R, Kalliomaki M, Salminen S, Isolauri E. Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2013 Nov;163(5):1272-7.e1-2. doi: 10.1016/j.jpeds.2013.05.035. Epub 2013 Jul 31.

Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012 Sep;96(3):544-51. doi: 10.3945/ajcn.112.037382. Epub 2012 Jul 25.

Grzeskowiak L, Collado MC, Mangani C, Maleta K, Laitinen K, Ashorn P, Isolauri E, Salminen S. Distinct gut microbiota in southeastern African and northern European infants. J Pediatr Gastroenterol Nutr. 2012 Jun;54(6):812-6. doi: 10.1097/MPG.0b013e318249039c.

Grzeskowiak L, Gronlund MM, Beckmann C, Salminen S, von Berg A, Isolauri E. The impact of perinatal probiotic intervention on gut microbiota: double-blind placebo-controlled trials in Finland and Germany. Anaerobe. 2012 Feb;18(1):7-13. doi: 10.1016/j.anaerobe.2011.09.006. Epub 2011 Sep 29.

Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology. 2008;93(4):236-40. doi: 10.1159/000111102. Epub 2007 Nov 16.

• ClinicalTrials.gov Identifier: NCT00167700
• Other Study ID Numbers: 15214
• First Posted: September 14, 2005
• Last Update Posted: October 4, 2012
• Last Verified: September 2012

Keywords provided by University of Turku:

atopic disease; probiotics; gut microbiota; allergy; nutrition; growth; allergic rhinitis; atopic sensitization; risk-markers of life-style related diseases

Additional relevant MeSH terms:

Overweight; Hypersensitivity; Overnutrition; Nutrition Disorders; Body Weight; Immune System Diseases