Clinical trial NCT02721225: Prebiotic in Preventing Low Birth Weight
Official title: Promoting Healthy Foetal and Post Natal Growth by Modulating Vaginal or Gut Micro Biota With Supplementation of Prebiotic Agent ( Fructooligosaccharide) in Pregnant Women- a Randomized Double Blind Community Based Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Birth Weight <2500gm
Genitourinary Tract Infection
Lead sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Swedish International Development Cooperation Agency (SIDA)
First posted: 2016-03-29
Enrollment: 210
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: More than 20 million infants worldwide, representing 16 per cent of all births, are born with low birth weight, 96 per cent of them in developing countries. Bangladesh having one of the highest incidence rate (21.6%) in the world.The short-term consequences of LBW is 12 times higher perinatal mortality. It is estimated that LBW causes 60 to 80 % of neonatal deaths. For the survivors, the effects are long lasting and largely irreversible. Infants born LBW are at 2-4 times greater risk to develop acute diarrhea, pneumonia or acute respiratory tract infection than their normal birth weight counterparts. Adults born with LBW suffer increased risk of high blood pressure, coronary heart disease (CHD), non insulin dependent diabetes mellitus, obstructive lung diseases, or renal damage.

Genitourinary (GU) infection, as a major risk factor for low birth weight deliveries affecting a very large number of women both in the industrialized and the developing world. In Bangladesh, there was a high incidence of UTI in 21-25 years age group (44.61%). The bottom line for GU infection is that lactobacilli, healthy bacteria lose their dominant. Recently, the protective role of the commensal microbiota has come into focus for its infection-inhibiting function. Lactobacilli that colonize the gastrointestinal tract or vagina can either significantly modulate the colonic microbiota by increasing the number of specific prebiotic bacteria such as lactobacilli and bifidobacteria or reducing undesired intestinal colonization of pathogenic bacteria. Prebiotic like Fructooligosaccharide (FOS) is known to promote growth of normal healthy flora like lactobacilli (LAB). FOS supplementation in early pregnancy improves vaginal or gut microflora with LAB , which will control GU infection and improve pregnancy outcome and promote infant's growth and development

Detailed description: Medical research over the last ten years has identified genitourinary (GU) infection, as a major risk factor for low birth weight deliveries affecting a very large number of women both in the industrialized and the developing world. It is estimated that up to about 1 billion of women are affected annually by urinary infections worldwide. Urinary tract infections (UTI) are also most common bacterial infections during pregnancy. In Bangladesh, there was a high incidence of UTI in 21-25 years age group (44.61%). The bottom line for GU infection is that lactobacilli, healthy bacteria lose their dominant.

The role of normal vaginal micro-biota in urogenital health Recently, the protective role of the commensal microbiota has come into focus for its infection-inhibiting function. Lactobacilli are now the favourite probiotic ("health promoting") bacteria. There are clinical evidence to show that Lactobacillus strains GR-1 and RC-14 were shown to reduce UTI, BV and infections associated with yeast pathogens.

Fructoligosacharride, a prebiotic agent At present, considerable attention is focused on determining ways to increase the number of probiotic microorganisms including lactobacilli that colonize the gastrointestinal tract or vagina. Prebiotics are substances that can either significantly modulate the colonic microbiota by increasing the number of specific probiotic bacteria such as lactobacilli and bifidobacteria or reducing undesired intestinal colonization of pathogenic bacteria by mimicking their attachment sites on the intestinal mucosa.

Design and methods In a, double- blind, placebo- controlled study, 210 early pregnant community women (6-12 weeks gestation) will be randomized to either FOS or placebo, administered orally, 6g/day for 6 months. Vaginal smear and urine samples will be followed for LAB using Nugent's score and to exclude UTI respectively. Birth events including weight will be documented. Stool or nasopharyngeal samples from their infants will be obtained at week-24, 30, and 36 to see levels of LAB. Anthropometry and diseases morbidity will be monitored during infancy.

Outcome measures/variables:

* Primary: 1. Incidence of LBW (birth weight below 2500 gram)
* Secondary 1. Rate of vaginal and intestinal colonization of LAB and/or GU infection at week 12, 24, 36 gestation and gain in z-score (weight for height, weight for age and height for age) of infant from birth

Eligibility criteria: Inclusion Criteria:(i) Age: 18-35 years (ii) Missed period : 6-12 weeks (iii) Positive pregnancy test by dip stick method in a morning urine sample (iv) Parity: any but with history of previous normal delivery (v) Weight: Body Mass Index greater than 18.5 but less than 35 (vi) Past obstetric history: Uncomplicated pregnancy, unremarkable medical and obstetric Conditions. (vii) Written informed consent witnessed by husband or legal guardian (thumb impression for those who are illiterate)

Exclusion Criteria:

Exclusion criteria The exclusion criteria will be (i) known previous H/O gestational diabetes and pre-eclamptic toxaemia (PET), (ii) any systemic disorder or chronic illness (iii) history of previous major gynaecological problem or treatment i.e., myomectomy, hysterotomy, knife cone biopsy etc.

(iv) uterine/vaginal abnormality or (v) 3 or more previous consecutive spontaneous abortions and no subsequent non vaginal delivery, etc.).

(vi) Hb level ( \< 7 gm/dL), and/or oedema (vii) History of taking antibiotic within 3 weeks prior to this study (viii) Complications in previous pregnancy (stillbirth, preterm labour, complicated instrumental delivery, retained placenta, 3°/ 4° perineal tear, transverse lie, placental abruption, Previous baby of \<2.5 kg / \>4.5 kg) (ix) Women unwilling to comply with study protocol (x) Presence of UTI or bacteriuria in a morning mid stream fresh urine sample (xi) Presence of abnormal vaginal flora (Nugent score \>7) (xii) History of irregular bleeding due to injectable Depo-Provera

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Primary outcomes:
measure: 1. Infant birth weight
timeFrame: just after birth
measure: Gestational age
timeFrame: upto 40 weeks of pregnancy
Secondary outcomes:
measure: Vaginal colonization of Lactobacillus (LAB)
timeFrame: at 12, 18 and 30 weeks of gestation
measure: Intestinal Colonization of LAB
timeFrame: at 12, 24 and 36 weeks of gestation from pregnant women and at birth from the infant
measure: Rate of Genito-urinary (GU) infection
timeFrame: at 12, 18, 24 and 36 weeks of pregnancy
measure: Gain in Z-score of infant from birth
timeFrame: from birth to 3 months of age of infant
measure: Incidence of Acute respiratory infection and diarrhoea
timeFrame: From birth to 3 months of age
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Shafiqul Alam Sarker
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Shafiqul A Sarker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: