Nutrition and Pregnancy Intervention Study

Placebo-controlled Intervention Study for Maternal and Child Health

A randomized double-blind placebo controlled intervention study with pregnant obese women (n=440) will be conducted. The intervention will involve consumption of fish oil and/or probiotic capsules from early pregnancy until 6 months after delivery.

The aim of the study is firstly to investigate the effects of the supplements on the risk of gestational diabetes mellitus and obesity in the women and secondly to modify the risk markers of allergy and obesity in children of the women. Also the underlying metabolic mechanisms will be investigated.

Follow up visits at child's age of 5 to 6 years will be conducted to evalute long-term effects on maternal and child health. The aim is to investigate the impact of dietary intervention, diet, maternal overweight/obesity and gestational diabetes status as well as gut microbiota and metabolism during pregnancy on maternal and child's health, allergy and child neuropsychological development.

Study Overview

• Status: Completed
• Conditions: Liver Diseases; Obesity; Pregnancy; Neurodevelopmental Disorders; Type2 Diabetes; Adiposity; Cardiovascular Risk Factor; Gestational Diabetes Mellitus; Eating Behavior; Cognitive Developmental Disorders
• Intervention / Treatment: Dietary supplement: Comparison of probiotics, fish oil and their combination to placebo

• Study Type: Interventional
• Enrollment (Actual): 439
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20521
    • Turku University Hospital
  • Turku, Finland, 20014
    • University of Turku

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• pregnant, less than 17 gestational weeks
• overweight
• healthy

Exclusion Criteria:

• Diabetes (type 1 or 2)
• Coeliac disease
• Increased bleeding tendency

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Probiotic; Comparison of probiotics, fish oil and their combination to placebo	Dietary supplement: Comparison of probiotics, fish oil and their combination to placebo; Double-blind randomized placebo controlled intervention; Other Names: Lactobacillus and Bifidobacterium; Fish oil; Placebo, microcrystalline cellulose; Placebo, medium-chain triglycerides
Active Comparator: Fish oil; Comparison of probiotics, fish oil and their combination to placebo	Dietary supplement: Comparison of probiotics, fish oil and their combination to placebo; Double-blind randomized placebo controlled intervention; Other Names: Lactobacillus and Bifidobacterium; Fish oil; Placebo, microcrystalline cellulose; Placebo, medium-chain triglycerides
Active Comparator: Probiotics and Fish oil; Comparison of probiotics, fish oil and their combination to placebo	Dietary supplement: Comparison of probiotics, fish oil and their combination to placebo; Double-blind randomized placebo controlled intervention; Other Names: Lactobacillus and Bifidobacterium; Fish oil; Placebo, microcrystalline cellulose; Placebo, medium-chain triglycerides
Placebo Comparator: Placebo; Comparison of probiotics, fish oil and their combination to placebo	Dietary supplement: Comparison of probiotics, fish oil and their combination to placebo; Double-blind randomized placebo controlled intervention; Other Names: Lactobacillus and Bifidobacterium; Fish oil; Placebo, microcrystalline cellulose; Placebo, medium-chain triglycerides

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prevalence of gestational diabetes mellitus, GDM	Assessed at gestational weeks 24-28
Fasting glucose levels	assessed at the third trimester of pregnancy
Prevalence of allergy in child	assessed at 12 and 24 months of age

Secondary Outcome Measures

Outcome Measure	Time Frame
Need for medication for management of gestational diabetes mellitus GDM (insulin or metformin)	During pregnancy
Body composition of mother	During and after pregnancy
Immunologic and metabolic markers	During and after pregnancy
Fecal microbiota	Before, during and after intervention
Fasting serum glucose (mmol/l) (mother/ child)	Assessed at 5-6 years postpartum
Fasting serum insulin (mU/l) (mother/child)	Assessed at 5-6 years postpartum
Number of women with prediabetes using criteria defined by American Diabetes Association	Assessed at 5-6 years postpartum
Number of women with metabolic syndrome using criteria defined by The International Diabetes Federation	Assessed at 5-6 yrs postpartum
Risk for Type 2 diabetes using questionnaire (mother)	Assessed at 5-6 yrs postpartum
Serum high sensitive C-reactive protein (mg/l) (mother/child)	Assessed at 5-6 yrs postpartum
Lipid metabolism (fasting cholesterol (mmol/l), fasting triglycerides (mmol/l), fasting HDL-cholesterol (mmol/l), fasting LDL-cholesterol (mmol/l) (mother/child)	Assessed at 5-6 yrs postpartum
Serum metabolomics by NMR (mother/child)	assessed at 5-6 yrs postpartum
Obesity by body mass index (mother/child) and body fat percentage by air displacement plethysmography (mother/child)	Assessed at 5-6 yrs postpartum
Carotid intima media thickness by ultra sound (mother/child)	Assessed at 5-6 yrs postpartum
Retinal microvasculature by digital retinal imaging (mother)	Assessed at 5-6 yrs postpartum
Liver fat by ultra sound (mother)	Assessed at 5-6 yrs postpartum
Liver health by ALAT (child/mother)	Assessed at 5-6 yrs postpartum
Fecal microbiota composition (mother/child)	Assessed at 5-6 yrs postpartum
Dietary intake of foods and nutrients and diet pattern calculated from food diaries, dietary quality index and food frequencies (assessed by questionnaires)/mother and child	Assessed at 5-6 yrs postpartum
Eating behavior by Three Factor Eating Questionnaire, Neofobia and Comprehensive Feeding Practices Questionnaire, Child Feeding Questionnaire, Child Eating Behaviour Questionnaire (child)	Assessed at 5-6 yrs postpartum
Motor development by Movement Assessment Battery for Children and by Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) (Child)	Assessed at 5-6 yrs postpartum
Cognitive development by Cantab test and Wechsler Preschool and Primary Scale of Intelligence (child)	Assessed at 5-6 yrs postpartum
Child effortful/emotionally-driven inhibition by the Forbidden Toy task and by Delay of gratification test (child)	Assessed at 5-6 yrs postpartum
Social emotional assessment by Behavior Rating Inventory of Executive Functions (child)	Assessed at 5-6 yrs postpartum
The child's social competence by Multisource Assessment of Children's Social Competence questionnaire and children's behavioral, social, and attention problems by the Child Behavior Checklist. (child)	Assessed at 5-6 yrs postpartum
Infant temperament, Child Behavior Questionnaire (child)	Assessed at 5-6 yrs postpartum
Child growth measured from weight (kg) and length (cm)	Assessed at 5-6 yrs postpartum
Atopy by serum antigens and asthma by spirometry (child)	Assessed at 5-6 yrs postpartum
Immunological cells from blood (child)	Assessed at 5-6 yrs postpartum
Physical activity by questionnaires and activity monitor	Assessed at 5-6 yrs postpartum

Other Outcome Measures

Outcome Measure	Time Frame
Body composition, growth, development and metabolic markers of the child	0 to 24 months of age

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: University of Turku
• Investigators: Principal Investigator: Kirsi Laitinen, University of Turku

Publications and helpful links

General Publications

• Houttu N, Mokkala K, Saleem WT, Virtanen S, Juhila J, Koivuniemi E, Pellonpera O, Tertti K, Luokola P, Sorsa T, Salonen A, Lahti L, Laitinen K. Potential pathobionts in vaginal microbiota are affected by fish oil and/or probiotics intervention in overweight and obese pregnant women. Biomed Pharmacother. 2022 May;149:112841. doi: 10.1016/j.biopha.2022.112841. Epub 2022 Mar 28.
• Lotankar M, Mokkala K, Houttu N, Koivuniemi E, Sorensen N, Nielsen HB, Munukka E, Lahti L, Laitinen K. Distinct Diet-Microbiota-Metabolism Interactions in Overweight and Obese Pregnant Women: a Metagenomics Approach. Microbiol Spectr. 2022 Apr 27;10(2):e0089321. doi: 10.1128/spectrum.00893-21. Epub 2022 Mar 28.
• Mokkala K, Gustafsson J, Vahlberg T, Vreugdenhil ACE, Ding L, Shiri-Sverdlov R, Plat J, Laitinen K. Serum CathepsinD in pregnancy: Relation with metabolic and inflammatory markers and effects of fish oils and probiotics. Nutr Metab Cardiovasc Dis. 2022 May;32(5):1292-1300. doi: 10.1016/j.numecd.2022.02.011. Epub 2022 Feb 23.
• Pajunen L, Korkalo L, Koivuniemi E, Houttu N, Pellonpera O, Mokkala K, Shivappa N, Hebert JR, Vahlberg T, Tertti K, Laitinen K. A healthy dietary pattern with a low inflammatory potential reduces the risk of gestational diabetes mellitus. Eur J Nutr. 2022 Apr;61(3):1477-1490. doi: 10.1007/s00394-021-02749-z. Epub 2021 Nov 30.
• Mokkala K, Houttu N, Koivuniemi E, Sorensen N, Nielsen HB, Laitinen K. GlycA, a novel marker for low grade inflammation, reflects gut microbiome diversity and is more accurate than high sensitive CRP in reflecting metabolomic profile. Metabolomics. 2020 Jun 20;16(7):76. doi: 10.1007/s11306-020-01695-x.
• Mokkala K, Vahlberg T, Pellonpera O, Houttu N, Koivuniemi E, Laitinen K. Distinct Metabolic Profile in Early Pregnancy of Overweight and Obese Women Developing Gestational Diabetes. J Nutr. 2020 Jan 1;150(1):31-37. doi: 10.1093/jn/nxz220.
• Pellonpera O, Mokkala K, Houttu N, Vahlberg T, Koivuniemi E, Tertti K, Ronnemaa T, Laitinen K. Efficacy of Fish Oil and/or Probiotic Intervention on the Incidence of Gestational Diabetes Mellitus in an At-Risk Group of Overweight and Obese Women: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial. Diabetes Care. 2019 Jun;42(6):1009-1017. doi: 10.2337/dc18-2591. Epub 2019 Apr 9.
• Mokkala K, Roytio H, Munukka E, Pietila S, Ekblad U, Ronnemaa T, Eerola E, Laiho A, Laitinen K. Gut Microbiota Richness and Composition and Dietary Intake of Overweight Pregnant Women Are Related to Serum Zonulin Concentration, a Marker for Intestinal Permeability. J Nutr. 2016 Sep;146(9):1694-700. doi: 10.3945/jn.116.235358. Epub 2016 Jul 27.
• 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.

Helpful Links

• University of Turku
• Turku University Hospital
• Research group www-pages

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: August 12, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimate): August 14, 2013

Study Record Updates

• Last Update Posted (Estimate): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Probiotics; Nutrition; Fish oil
• Additional Relevant MeSH Terms: Mental Disorders; Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Liver Diseases; Diabetes Mellitus; Disease; Developmental Disabilities; Neurodevelopmental Disorders; Diabetes, Gestational
• Other Study ID Numbers: T166/2012