Objectives of the study: Primary outcome: To compare the proportion of early preterm labour between high dose DHA (1000mg/day) and low dose DHA 200mg/day Secondary outcome: To compare the following between high dose DHA (1000mg/day) and low dose DHA 200mg/day 1. Women with utero-placental insufficiency (IUGR, Preeclampsia) 2. Gestational Age at deliver 3. Birth weight 4. Gestational diabetes mellitus (GDM) 5. Pregnancy outcome: Spontaneous, Induced labour and LSCS. Study design: Randomised controlled trial, prospective enrolment & data collection Study period: One year Sampling: Considering the primary objective is to compare the proportion of early preterm labour between high dose DHA (1000mg/day) and low dose DHA 200mg/day, sample size was calculated. Following sample size formula was used: 1 Where n is the calculated sample size p is the expected proportion (pA = 0.089 and pB = 0.070) α is Type I error = 5% β is Type II error, meaning 1�’β is power = 90% Calculated sample size is 4247 and rounded to 4500. In each treatment group minimum of 2250 subjects will be considered. (23) Computerized randomisation schedule will be generated for each centre separately. Randomized treatment allocation will be done by sealed opaque envelop method. Inclusion criteria 1. Pregnant females 18 – 40 years 2. Gestational Age 12 - 20 weeks 3. Singleton pregnancy, irrespective of co-morbidities 4. Dietary intake of DHA is <200 mg/day 5. Available by telephone, to verify dietary compliance 6. South Asian population Exclusion criteria: 1. Women with allergy to any component of DHA product (Including algae), soybean oil or corn oil 2. Uterine anomalies Women with congenital foetal anomalies at 20 weeks or early, which may require termination of pregnancy Details of control group: Women assigned to this group will fulfil the inclusion criteria and take 200mg of DHA. Detail of study group: Women assigned to this group will fulfil the inclusion criteria and will receive high dose DHA 1000mg. Statistical analysis: Appropriate Statistical test will be used to analyse the data collected. All p values less than 0.05 will be considered significant. Study layout and methodology: Pregnant women coming to either of three centres of Cloudnine hospital (Jayanagar branch, old airport road branch or Malleshwaram branch) will be considered as participants. If these women satisfy the eligibility criteria, they will be approached in the outpatient department, by respective centre CRE’s (who will work in group of two) with a brochure, explaining the study. The brochure will provide basic idea about what is DHA, its effects, advantages in pregnancy, disadvantages, adverse side effects and what the study is about. If the pregnant women want to be included in the study, consent, both oral and written will be taken. Once the women have consented to be a part of the study, they will be referred to respective centre dietician. The chief dietician will (who work in group of two) present the patient with a questionnaire. Personal information like Age, Height, Weight, Diet preference will be collected along with Food frequency during third trimester which focuses on Docosahexaenoic acid. (refer annexure 1) Each centre is expected to enrol 4-5 patients per day. If the DHA is <200mg/day will be included in the study. Screening Method: Materials: - Gadget Hero’s Wall Mounted scale: Height will be measured using this scale - Digital Weighing Scale: Weight will be calculated using this weighing scale. - Standardised spoons and cups: Serving size and amount is measured using as 1 teaspoon – 5ml, 1 tablespoon 15ml, one cup – 200ml, Glass -250ml - Questionnaire: A questionnaire is designed which has general lifestyle questions, food frequency questionnaire regarding DHA, parity, food preference. Method: - Face to Face interview would be done and data will be collected. - Once the questionnaire is filled, the DHA intake would be measured using the IFCT or USDA values. - The patients lesser than 200mg of DHA will be sent to next stage of trial. Participants will be allotted to treatment group by computerized randomization schedule generated for each centre separately. Randomized treatment allocation will be done by sealed opaque envelop method. Women enrolled in either group need not pay to procure the supplement. It will be provided free of cost. Drug Dispatch: Investigator will personally hand over the drug to the participants depending on their group they belong to, when they visit the hospital for clinical visit. No interim study will be done. Included women will provide a blood sample collected on “filter paper – similar to Guthrie cards†for fatty acid analysis of RBC (RBC-PL fatty acid). The blood collected will not be stored for further use. Blood cards will be sent to Lipid Lab, room GN21, main Waite building, Waite campus, The University of Adelaide, Urrbane SA 5064, Australia. All blood test for fatty acid analysis will be free of cost. Blood samples will be collected from all participants at enrolment, at 32-34 weeks of pregnancy and following day of delivery. In case of allergic reaction or severe side effects requiring medical assistance, women need to report to the Principal investigator, whose number will be shared by the centre CRE. Financial assistance will be given only for treatment of side effects or allergic reactions if any occurring because of supplement given (high or low dose of DHA) during the study. All the possible side effects and relevant information has been provided in the brochure (patient information leaflet). Annexure 2- Questionnaire Maternal general and medical history - History of previous preterm labour (as they are more likely to have preterm labour in this pregnancy) - Parity history (number of pregnancies in the past and their outcomes) - History of pre-existing chronic hypertension, diabetes, renal failure. - Height (Ht) - Weight (Wt.) - BMI (body mass index) - BP (blood pressure<130/80mmHg is considered normal, while >140/90 mmHg is abnormal) - Urine albumin (an indicator of proteinuria, a component of pre-eclampsia) - GTT (glucose tolerance test- where abnormal values indicate gestational diabetes mellitus) - Vaginal discharge (an indicator of vaginal infection) - HB % (haemoglobin values) - IUGR (intrauterine growth restriction) - Congenital anomalies (as they can be diagnosed from 12-20 weeks, and maybe a reason for termination of pregnancy) - Cervical length (as it is an indicator or premature labour) - UTI (urinary tract infection) The above-mentioned variables will help us to look at other possible causes of preterm labour. Like preeclampsia, GDM, anaemia, IUGR with or without Doppler changes, infection may be a cause of preterm labour. ANNEXURE 3: Information to be collected at the time of delivery. At the time of delivery, the following data will be collected - Blood sample for DHA - Date of delivery - Mode of deliver: 1. Vaginal: 2. Caesarean section - Spontaneous delivery: - Induction of labour 1. Prostaglandin type: 2. Oxytocin 3. Artificial rupture of membranes - Instrumental delivery: 1. Vacuum: 2. Forceps: 3. Kiwi cup - Estimated blood loss - Weight of the foetus - Sex of the foetus - Head circumference of the foetus - Length of the foetus - Hypoglycaemia - NICU admission(i/v/o: jaundice, sepsis, necrotising enterocolitis, oxygen requirement and duration, foetal distress, retinopathy of prematurity): specify ______________________________________________________________________________________________ |