title: The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy.
abstract: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum.
  
  
  
  The PiP Study is a two-centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 × 10(9) colony-forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action.
  
  
  
  The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum.
  
  
  
  Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12.
authors.affiliation: Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand. christine.barthow@otago.ac.nz.
authors.forename: Christine
authors.initials: C
authors.lastname: Barthow
authors.affiliation: Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Kristin
authors.initials: K
authors.lastname: Wickens
authors.affiliation: Department of Paediatrics, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stanley
authors.affiliation: Department of Paediatrics: Child and Youth Health, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Mitchell
authors.affiliation: Graduate School of Nursing, Midwifery and Health, Victoria University of Wellington, P O Box 7625, Newtown, Wellington, 6242, New Zealand.
authors.forename: Robyn
authors.initials: R
authors.lastname: Maude
authors.affiliation: Department of Obstetrics and Gynaecology, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Abels
authors.affiliation: Dean's Department, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Gordon
authors.initials: G
authors.lastname: Purdie
authors.affiliation: Department of Medicine, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Rinki
authors.initials: R
authors.lastname: Murphy
authors.affiliation: Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Stone
authors.affiliation: Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Janice
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Fiona
authors.initials: F
authors.lastname: Hood
authors.affiliation: Department of Paediatrics: Child and Youth Health, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Judy
authors.initials: J
authors.lastname: Rowden
authors.affiliation: Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Phillipa
authors.initials: P
authors.lastname: Barnes
authors.affiliation: Immunology Department, Auckland Hospital, Private Bag 92024, Auckland Mail Centre, Auckland, 1142, New Zealand.
authors.forename: Penny
authors.initials: P
authors.lastname: Fitzharris
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Victoria, 3052, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Craig
authors.affiliation: Department of Paediatrics: Child and Youth Health, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Slykerman
authors.affiliation: Department of Medicine, University of Otago Wellington, PO Box 7343, Wellington South, 6242, New Zealand.
authors.forename: Julian
authors.initials: J
authors.lastname: Crane
mesh_terms: D000328:Adult; D001942:Breast Feeding; D019587:Dietary Supplements; D004311:Double-Blind Method; D004485:Eczema / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000209:etiology / Q000517:prevention & control*; D052201:Lacticaseibacillus rhamnosus; D000068097:Maternal Health; D039382:Maternal Nutritional Physiological Phenomena; D009520:New Zealand; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control*; D011295:Prenatal Care / Q000379:methods*; D019936:Probiotics / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: Atopy; Gestational diabetes; Infant eczema; Postpartum depression; Pregnancy; Probiotic; Vaginal infections