Effects of probiotics (Vivomixx®) in obese pregnant women and their newborn: study protocol for a randomized controlled trial

Sofie Ingdam Halkjaer, Lisbeth Nilas, Emma Malchau Carlsen, Dina Cortes, Thórhallur Ingi Halldórsson, Sjúrdur Frodi Olsen, Anders Elm Pedersen, Karen Angeliki Krogfelt, Andreas Munk Petersen, Sofie Ingdam Halkjaer, Lisbeth Nilas, Emma Malchau Carlsen, Dina Cortes, Thórhallur Ingi Halldórsson, Sjúrdur Frodi Olsen, Anders Elm Pedersen, Karen Angeliki Krogfelt, Andreas Munk Petersen

Abstract

Background: Maternal obesity is associated with increased risks of adverse pregnancy-related complications and outcomes for both mothers and infants. Overweight and obese women have an increased risk of pregnancy-induced hypertension, preeclampsia and gestational diabetes mellitus (GDM). Infant Body Mass index (BMI) and the risk of obesity in adulthood are related to maternal gestational weight gain (GWG). Preventive lifestyle and dietary interventions are time-consuming and do not always reduce GWG or the risk of maternal pregnancy complications. Recent research has indicated that the gut microbiota may play a significant role in the development of obesity. Some studies have indicated that the daily consumption of probiotics may reduce the risk of preeclampsia, maintain serum insulin levels and reduce the frequency of GDM in pregnant women. The aims of this study are to investigate whether daily probiotic supplements in obese women during pregnancy can limit gestational weight gain, improve glucose homeostasis and thereby improve maternal, fetal and infant health outcomes.

Methods: A pilot study including 50 obese pregnant nulliparous women with a prepregnancy BMI of between 30 and 35 kg/m2 will be randomized to receive daily probiotics (four capsules of Vivomixx®; total of 450 billion CFU/day, including eight probiotic bacterial strains) or placebo from gestational age 14-20 weeks until delivery. The infants will be followed until 9 months of age. The women will be monitored by weight, blood, fecal, vaginal and urine samples, diet questionnaires and hospital record review. Primary outcomes are: maternal weight gain, glycated hemoglobin (HbA1c) level and changes in glucose concentration measured during an oral glucose tolerance test. Secondary outcomes are: microbiota and inflammatory markers in mother and child, pregnancy complications, pregnancy outcomes, physical activity and the body composition of the neonate.

Discussion: We expect to find alterations in the metabolic profiles, microbiota and possibly pregnancy outcomes. From a clinical point of view the effects of Vivomixx® could control weight gain and reduce complications during pregnancy by inducing changes in the gut microbiota. Furthermore, this intervention during pregnancy could influence the infant's microbiota, which could have important implications for infant development and health.

Trial registration: ClincalTrials.gov Identifier: NCT02508844 , registered on 11 May 2015.

Keywords: Gestational diabetes mellitus; Microbiota; Obesity; Pregnancy; Probiotics; Study protocol; Vivomixx®.

Figures

Fig. 1
Fig. 1
Study flow chart of the pilot study

References

    1. Ovesen P, Rasmussen S, Kesmodel U. Effect of prepregnancy maternal overweight and obesity on pregnancy outcome. Obstet Gynecol. 2011;118(2 Pt 1):305–12. doi: 10.1097/AOG.0b013e3182245d49.
    1. Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol. 2012;8(11):639–49. doi: 10.1038/nrendo.2012.96.
    1. Leddy MA, Power ML, Schulkin J. The impact of maternal obesity on maternal and fetal health. Rev Obstet Gynecol. 2008;1(4):170–8.
    1. Catalano PM, McIntyre HD, Cruickshank JK, McCance DR, Dyer AR, Metzger BE, et al. The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes. Diabetes Care. 2012;35(4):780–6. doi: 10.2337/dc11-1790.
    1. Hill JC, Krishnaveni GV, Annamma I, Leary SD, Fall CHD. Glucose tolerance in pregnancy in South India: relationships to neonatal anthropometry. Acta Obstet Gynecol Scand. 2005;84(2):159–65. doi: 10.1111/j.0001-6349.2005.00670.x.
    1. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115(3):e290–6. doi: 10.1542/peds.2004-1808.
    1. WHO European action plan for food and nutrition policy 2007–2012 [Internet]. Available from: . Accessed 6 Jan 2014.
    1. Schack-Nielsen L, Michaelsen KF, Gamborg M, Mortensen EL, Sørensen TIA. Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood. Int J Obes. 2009;34(1):67–74. doi: 10.1038/ijo.2009.206.
    1. Carlsen EM, Renault KM, Nørgaard K, Nilas L, Jensen JEB, Hyldstrup L, et al. Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score. Acta Paediatr Oslo Nor 1992. 2014;103(9):939–45.
    1. Gesche J, Nilas L. Pregnancy outcome according to pre-pregnancy body mass index and gestational weight gain. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2015;129(3):240–3. doi: 10.1016/j.ijgo.2014.12.013.
    1. Renault KM, Nørgaard K, Nilas L, Carlsen EM, Cortes D, Pryds O, et al. The Treatment of Obese Pregnant Women (TOP) study: a randomized controlled trial of the effect of physical activity intervention assessed by pedometer with or without dietary intervention in obese pregnant women. Am J Obstet Gynecol. 2014;210(2):134. doi: 10.1016/j.ajog.2013.09.029.
    1. Morisset A-S, St-Yves A, Veillette J, Weisnagel SJ, Tchernof A, Robitaille J. Prevention of gestational diabetes mellitus: a review of studies on weight management. Diabetes Metab Res Rev. 2010;26(1):17–25. doi: 10.1002/dmrr.1053.
    1. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–14. doi: 10.1038/nrgastro.2014.66.
    1. Delzenne NM, Neyrinck AM, Bäckhed F, Cani PD. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011;7(11):639–46. doi: 10.1038/nrendo.2011.126.
    1. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–23. doi: 10.1073/pnas.0407076101.
    1. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31. doi: 10.1038/nature05414.
    1. Diamant M, Blaak EE, de Vos WM. Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev Off J Int Assoc Study Obes. 2011;12(4):272–81. doi: 10.1111/j.1467-789X.2010.00797.x.
    1. Kalliomäki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87(3):534–8.
    1. Lobstein T, Baur L, Uauy R, IASO International Obesity TaskForce Obesity in children and young people: a crisis in public health. Obes Rev Off J Int Assoc Study Obes. 2004;5(Suppl 1):4–104. doi: 10.1111/j.1467-789X.2004.00133.x.
    1. Brantsaeter AL, Myhre R, Haugen M, Myking S, Sengpiel V, Magnus P, et al. Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian Mother and Child Cohort Study. Am J Epidemiol. 2011;174(7):807–15. doi: 10.1093/aje/kwr168.
    1. Asemi Z, Samimi M, Tabassi Z, Naghibi Rad M, Rahimi Foroushani A, Khorammian H, et al. Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial. Eur J Clin Nutr. 2013;67(1):71–4. doi: 10.1038/ejcn.2012.189.
    1. 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;103(12):1792–9. doi: 10.1017/S0007114509993898.
    1. Corridoni D, Pastorelli L, Mattioli B, Locovei S, Ishikawa D, Arseneau KO, et al. Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism. PLoS One. 2012;7(7):e42067. doi: 10.1371/journal.pone.0042067.
    1. Ng SC, Plamondon S, Kamm MA, Hart AL, Al-Hassi HO, Guenther T, et al. Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis. Inflamm Bowel Dis. 2010;16(8):1286–98. doi: 10.1002/ibd.21222.
    1. Yadav H, Lee J-H, Lloyd J, Walter P, Rane SG. Beneficial metabolic effects of a probiotic via butyrate induced GLP-1 secretion. J Biol Chem. 2013;288:25088–97. doi: 10.1074/jbc.M113.452516.
    1. Rajkumar H, Mahmood N, Kumar M, Varikuti SR, Challa HR, Myakala SP. Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial. Mediators Inflamm. 2014;2014:348959. doi: 10.1155/2014/348959.
    1. Alisi A, Bedogni G, Baviera G, Giorgio V, Porro E, Paris C, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014;39(11):1276–85. doi: 10.1111/apt.12758.
    1. Vitali B, Cruciani F, Baldassarre ME, Capursi T, Spisni E, Valerii MC, et al. Dietary supplementation with probiotics during late pregnancy: outcome on vaginal microbiota and cytokine secretion. BMC Microbiol. 2012;12:236. doi: 10.1186/1471-2180-12-236.
    1. Olsen SF, Mikkelsen TB, Knudsen VK, Orozova-Bekkevold I, Halldórsson TI, Strøm M, et al. Data collected on maternal dietary exposures in the Danish National Birth Cohort. Paediatr Perinat Epidemiol. 2007;21(1):76–86. doi: 10.1111/j.1365-3016.2007.00777.x.
    1. Crouter SE, Schneider PL, Karabulut M, Bassett DR., Jr Validity of 10 electronic pedometers for measuring steps, distance, and energy cost. Med Sci Sports Exerc. 2003;35(8):1455–60. doi: 10.1249/01.MSS.0000078932.61440.A2.
    1. Aagaard K, Petrosino J, Keitel W, Watson M, Katancik J, Garcia N, et al. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J Off Publ Fed Am Soc Exp Biol. 2013;27(3):1012–22.
    1. Klindworth A, Pruesse E, Schweer T, Peplies J, Quast C, Horn M, et al. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2013;41(1):e1. doi: 10.1093/nar/gks808.
    1. Marsál K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr Oslo Nor 1992. 1996;85(7):843–8.
    1. de Knegt VE, Carlsen EM, Bech Jensen J-E, Lade Rasmussen AM, Pryds O. DXA performance in a pediatric population: precision of body composition measurements in healthy term-born infants using dual-energy X-ray absorptiometry. J Clin Densitom Off J Int Soc Clin Densitom. 2015;18(1):117–23. doi: 10.1016/j.jocd.2014.08.004.
    1. Lee JH, Moon G, Kwon HJ, Jung WJ, Seo PJ, Baec TY, et al. Effect of a probiotic preparation (VSL#3) in patients with mild to moderate ulcerative colitis. Korean J Gastroenterol Taehan Sohwagi Hakhoe Chi. 2012;60(2):94–101. doi: 10.4166/kjg.2012.60.2.94.
    1. Sood A, Midha V, Makharia GK, Ahuja V, Singal D, Goswami P, et al. The probiotic preparation VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2009;7(11):1202–9.
    1. Tursi A, Brandimarte G, Papa A, Giglio A, Elisei W, Giorgetti GM, et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2010;105(10):2218–27. doi: 10.1038/ajg.2010.218.
    1. Ebrahimi-Mameghani M, Sanaie S, Mahmoodpoor A, Hamishehkar H. Effect of a probiotic preparation (VSL#3) in critically ill patients: a randomized, double-blind, placebo-controlled trial (Pilot Study) Pak J Med Sci. 2013;29(2):490–4.
    1. Rincón D, Vaquero J, Hernando A, Galindo E, Ripoll C, Puerto M, et al. Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites. Liver Int Off J Int Assoc Study Liver. 2014;34:1504–12.
    1. Gupta N, Kumar A, Sharma P, Garg V, Sharma BC, Sarin SK. Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial. Liver Int Off J Int Assoc Study Liver. 2013;33(8):1148–57.
    1. Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104(2):437–43. doi: 10.1038/ajg.2008.118.
    1. Huynh HQ, deBruyn J, Guan L, Diaz H, Li M, Girgis S, et al. Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: a pilot study. Inflamm Bowel Dis. 2009;15(5):760–8. doi: 10.1002/ibd.20816.
    1. Allen SJ, Jordan S, Storey M, Thornton CA, Gravenor M, Garaiova I, et al. Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy. J Nutr. 2010;140(3):483–8. doi: 10.3945/jn.109.117093.
    1. Dugoua J-J, Machado M, Zhu X, Chen X, Koren G, Einarson TR. Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. J Obstet Gynaecol Can JOGC J Obstétrique Gynécologie Can JOGC. 2009;31(6):542–52.
    1. Lindsay KL, Kennelly M, Culliton M, Smith T, Maguire OC, Shanahan F, et al. Probiotics in obese pregnancy do not reduce maternal fasting glucose: a double-blind, placebo-controlled, randomized trial. Am J Clin Nutr. 2014;99(6):1432–9. doi: 10.3945/ajcn.113.079723.
    1. Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 2011;140(6):1713–9. doi: 10.1053/j.gastro.2011.02.011.
    1. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118(2):511–21. doi: 10.1542/peds.2005-2824.
    1. Luoto R, Collado MC, Salminen S, Isolauri E. Reshaping the gut microbiota at an early age: functional impact on obesity risk? Ann Nutr Metab. 2013;63(Suppl 2):17–26. doi: 10.1159/000354896.
    1. Lindsay KL, Walsh CA, Brennan L, McAuliffe FM. Probiotics in pregnancy and maternal outcomes: a systematic review. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2013;26(8):772–8.
    1. Barrett HL, Dekker Nitert M, Conwell LS, Callaway LK. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2014;2:CD009951.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi