The impact of DocosaHexaenoic Acid supplementation during pregnancy and lactation on Neurodevelopment of the offspring in India (DHANI): trial protocol

Shweta Khandelwal, M K Swamy, Kamal Patil, Dimple Kondal, Monica Chaudhry, Ruby Gupta, Gauri Divan, Mahesh Kamate, Lakshmy Ramakrishnan, Mrutyunjaya B Bellad, Anita Gan, Bhalchandra S Kodkany, Reynaldo Martorell, K Srinath Reddy, Dorairaj Prabhakaran, Usha Ramakrishnan, Nikhil Tandon, Aryeh D Stein, Shweta Khandelwal, M K Swamy, Kamal Patil, Dimple Kondal, Monica Chaudhry, Ruby Gupta, Gauri Divan, Mahesh Kamate, Lakshmy Ramakrishnan, Mrutyunjaya B Bellad, Anita Gan, Bhalchandra S Kodkany, Reynaldo Martorell, K Srinath Reddy, Dorairaj Prabhakaran, Usha Ramakrishnan, Nikhil Tandon, Aryeh D Stein

Abstract

Background: Evidence suggests a strong association between nutrition during the first 1000 days (conception to 2 years of life) and cognitive development. Maternal docosahexaenoic acid (DHA) supplementation has been suggested to be linked with cognitive development of their offspring. DHA is a structural component of human brain and retina, and can be derived from marine algae, fatty fish and marine oils. Since Indian diets are largely devoid of such products, plasma DHA levels are low. We are testing the effect of pre- and post-natal DHA maternal supplementation in India on infant motor and mental development, anthropometry and morbidity patterns.

Methods: DHANI is a double-blinded, parallel group, randomized, placebo controlled trial supplementing 957 pregnant women aged 18-35 years from ≤20 weeks gestation through 6 months postpartum with 400 mg/d algal-derived DHA or placebo. Data on the participant's socio-demographic profile, anthropometric measurements and dietary intake are being recorded at baseline. The mother-infant dyads are followed through age 12 months. The primary outcome variable is infant motor and mental development quotient at 12 months of age evaluated by Development Assessment Scale in Indian Infants (DASII). Secondary outcomes are gestational age, APGAR scores, and infant anthropometry. Biochemical indices (blood and breast-milk) from mother-child dyads are being collected to estimate changes in DHA levels in response to supplementation. All analyses will follow the intent-to-treat principle. Two-sample t test will be used to test unadjusted difference in mean DASII score between placebo and DHA group. Adjusted analyses will be performed using multiple linear regression.

Discussion: Implications for maternal and child health and nutrition in India: DHANI is the first large pre- and post-natal maternal dietary supplementation trial in India. If the trial finds substantial benefit, it can serve as a learning to scale up the DHA intervention in the country.

Trial registration: The trial is retrospectively registered at clinicaltrials.gov ( NCT01580345 , NCT03072277 ) and ctri.nic.in ( CTRI/2013/04/003540 , CTRI/2017/08/009296 ).

Keywords: Development assessment scale for Indian infants (DASII); Docosahexaenoic acid (DHA); Maternal supplementation; Neurodevelopment; Newborn outcomes; Omega 3 fatty acids; Polyunsaturated fatty acids; Pregnancy outcomes; n3PUFA.

Conflict of interest statement

Ethical clearances were obtained from all participating institutions including: Chronic Disease Control (CCDC-IEC_04_2015), Public Health Foundation of India (TRC-IEC-261/15), Jawaharlal Nehru Medical College (MDC/IECHSR/2016–17/A-85) and All India Institute of Medical Sciences (IEC-28/17.11.2015). Written informed consent was obtained from each willing and eligible participant in presence of her close relative or friend.

Not Applicable.

The authors declare that they have no competing interests.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT Diagram

References

    1. Stenberg K, et al. Advancing social and economic development by investing in women's and children's health: a new global investment framework. Lancet. 2014;383(9925):1333–1354. doi: 10.1016/S0140-6736(13)62231-X.
    1. Veena SR, et al. Association between maternal nutritional status in pregnancy and offspring cognitive function during childhood and adolescence; a systematic review. BMC Pregnancy Childbirth. 2016;16:1–11
    1. Walker SP, et al. Child development: risk factors for adverse outcomes in developing countries. Lancet. 2007;369(9556):145–157. doi: 10.1016/S0140-6736(07)60076-2.
    1. Mendez MA, Adair LS. Severity and timing of stunting in the first two years of life affect performance on cognitive tests in late childhood. J Nutr. 1999;129(8):1555–1562. doi: 10.1093/jn/129.8.1555.
    1. Grantham-McGregor S. A review of studies of the effect of severe malnutrition on mental development. J Nutr. 1995;125(8 Suppl):2233s–2238s. doi: 10.1093/jn/125.suppl_8.2233S.
    1. Grantham-McGregor S, et al. Developmental potential in the first 5 years for children in developing countries. Lancet. 2007;369(9555):60–70. doi: 10.1016/S0140-6736(07)60032-4.
    1. Koblinsky M, et al. Quality maternity care for every woman, everywhere: a call to action. Lancet. 2016;388(10057):2307–2320. doi: 10.1016/S0140-6736(16)31333-2.
    1. Nyaradi A, et al. The role of nutrition in children's neurocognitive development, from pregnancy through childhood. Front Hum Neurosci. 2013;7:97. doi: 10.3389/fnhum.2013.00097.
    1. Al MD, et al. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr. 1995;74(1):55–68. doi: 10.1079/BJN19950106.
    1. Thomas Rajarethnem H, et al. Combined supplementation of choline and docosahexaenoic acid during pregnancy enhances neurodevelopment of fetal hippocampus. Neurol Res Int. 2017;2017:8748706. doi: 10.1155/2017/8748706.
    1. Kajarabille N, et al. Omega-3 LCPUFA supplement: a nutritional strategy to prevent maternal and neonatal oxidative stress. Matern Child Nutr. 2017;13(2):1–24
    1. Meldrum S, Simmer K. Docosahexaenoic acid and neurodevelopmental outcomes of term infants. Ann Nutr Metab. 2016;69(Suppl 1):22–28.
    1. Zhang W, et al. N-3 polyunsaturated fatty acids reduce neonatal hypoxic/ischemic brain injury by promoting phosphatidylserine formation and Akt signaling. Stroke. 2015;46(10):2943–2950. doi: 10.1161/STROKEAHA.115.010815.
    1. Makrides M, et al. Four-year follow-up of children born to women in a randomized trial of prenatal DHA supplementation. Jama. 2014;311(17):1802–1804. doi: 10.1001/jama.2014.2194.
    1. Makrides M, Smithers LG, Gibson RA. Role of long-chain polyunsaturated fatty acids in neurodevelopment and growth. Nestle Nutr Workshop Ser Pediatr Program. 2010;65:123–133. doi: 10.1159/000281154.
    1. Birch EE, et al. The DIAMOND (DHA intake and measurement of neural development) study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010;91(4):848–859. doi: 10.3945/ajcn.2009.28557.
    1. Ranade PS, Rao SS. Maternal diet, LCPUFA status and prematurity in indian mothers: A cross-sectional study. Functional Foods Health Disease. 2012;2(11):414–427.
    1. Muthayya S, et al. The effect of fish and omega-3 LCPUFA intake on low birth weight in Indian pregnant women. Eur J Clin Nutr. 2009;63(3):340–346. doi: 10.1038/sj.ejcn.1602933.
    1. Innis SM. Omega-3 fatty acid biochemistry: perspectives from human nutrition. Mil Med. 2014;179(11 Suppl):82–87. doi: 10.7205/MILMED-D-14-00147.
    1. Kilari AS, et al. Long chain polyunsaturated fatty acids in mothers and term babies. J Perinat Med. 2009;37(5):513–518. doi: 10.1515/JPM.2009.096.
    1. Dwarkanath P, et al. Polyunsaturated fatty acid consumption and concentration among south Indian women during pregnancy. Asia Pac J Clin Nutr. 2009;18(3):389–394.
    1. Simopoulos AP. The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac J Clin Nutr. 2008;17(Suppl 1):131–134.
    1. Mani I, Kurpad AV. Fats & fatty acids in Indian diets: time for serious introspection. Indian J Med Res. 2016;144(4):507–514.
    1. Rathod R, Kale A, Joshi S. Novel insights into the effect of vitamin B12 and omega-3 fatty acids on brain function. J Biomed Sci. 2016;23
    1. Lauritzen L, et al. DHA Effects in Brain Development and Function. Nutrients. 2016;8(1):1–17
    1. Makrides M, et al. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. Jama. 2010;304(15):1675–1683. doi: 10.1001/jama.2010.1507.
    1. Makrides M, et al. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. Jama. 2009;301(2):175–182. doi: 10.1001/jama.2008.945.
    1. Ramakrishnan U, Imhoff-Kunsch B, DiGirolamo AM. Role of docosahexaenoic acid in maternal and child mental health1234. Am J Clin Nutr. 2009;89(3):958s–962s. doi: 10.3945/ajcn.2008.26692F.
    1. Ramakrishnan U, et al. Prenatal supplementation with DHA improves attention at 5 y of age: a randomized controlled trial. Am J Clin Nutr. 2016;104(4):1075–1082. doi: 10.3945/ajcn.114.101071.
    1. Hibbeln JR, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet. 2007;369(9561):578–585. doi: 10.1016/S0140-6736(07)60277-3.
    1. Olsen SF, et al. Duration of pregnancy in relation to seafood intake during early and mid pregnancy: prospective cohort. Eur J Epidemiol. 2006;21(10):749–758. doi: 10.1007/s10654-006-9053-6.
    1. Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study. BMJ. 2002;324(7335):447. doi: 10.1136/bmj.324.7335.447.
    1. Olsen SF, et al. Frequency of seafood intake in pregnancy as a determinant of birth weight: evidence for a dose dependent relationship. J Epidemiol Community Health. 1993;47(6):436–440. doi: 10.1136/jech.47.6.436.
    1. Rogers LK, Valentine CJ, Keim SA. DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res. 2013;70(1):13–19. doi: 10.1016/j.phrs.2012.12.003.
    1. Peter S, Chopra S, Jacob JJ. A fish a day, keeps the cardiologist away! – a review of the effect of omega-3 fatty acids in the cardiovascular system. Indian J Endocrinol Metab. 2013;17(3):422–429. doi: 10.4103/2230-8210.111630.
    1. Hooper L, et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. 2004;(4):Cd003177.
    1. National Institute of Child Health and Human Development Early Child Care Research Network. Duration and developmental timing of poverty and children's cognitive and social development from birth through third grade. Child Dev. 2005;76(4):795–810.
    1. Pusceddu MM, et al. N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology. Int J Neuropsychopharmacol. 2016;19(12):1–23
    1. Black MM, et al. Early childhood development coming of age: science through the life course. Lancet. 2017;389(10064):77–90. doi: 10.1016/S0140-6736(16)31389-7.
    1. Chen GC, et al. N-3 long-chain polyunsaturated fatty acids and risk of all-cause mortality among general populations: a meta-analysis. Sci Rep. 2016;6:28165. doi: 10.1038/srep28165.
    1. Del Gobbo LC, et al. Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies. JAMA Intern Med. 2016;176(8):1155–1166. doi: 10.1001/jamainternmed.2016.2925.
    1. Gianni ML, et al. Randomized outcome trial of nutrient-enriched formula and neurodevelopment outcome in preterm infants. BMC Pediatr. 2014;14:74. doi: 10.1186/1471-2431-14-74.
    1. Bhave A, Bhargava R, Kumar R. Correlation between developmental quotients (DASII) and social quotient (Malin's VSMS) in Indian children aged 6 months to 2 years. J Paediatr Child Health. 2011;47(3):87–91. doi: 10.1111/j.1440-1754.2010.01894.x.
    1. Phatak AT, Khurana B. Baroda development screening test for infants. Indian Pedatrics. 1991;28(1):31–37.
    1. Bhave A, Bhargava R, Kumar R. Development and validation of a new Lucknow development screen for Indian children aged 6 months to 2 years. J Child Neurol. 2010;25(1):57–60. doi: 10.1177/0883073809336121.
    1. Godbole K, Barve S, Chaudhari S. Early predictors of neurodevelopmental outcome in high risk infants. Indian Pediatr. 1997;34(6):491–495.
    1. Juneja M, et al. Ages and stages questionnaire as a screening tool for developmental delay in Indian children. Indian Pediatr. 2012;49(6):457–461. doi: 10.1007/s13312-012-0074-9.
    1. Mukhopadhyay K, et al. Neurodevelopmental and behavioral outcome of very low birth weight babies at corrected age of 2 years. Indian J Pediatr. 2010;77(9):963–967. doi: 10.1007/s12098-010-0149-3.
    1. Lepage G, Roy CC. Direct transesterification of all classes of lipids in a one-step reaction. J Lipid Res. 1986;27(1):114–120.
    1. Elchalal U, et al. Postpartum umbilical cord blood collection for transplantation: a comparison of three methods. Am J Obstet Gynecol. 2000;182(1 Pt 1):227–232. doi: 10.1016/S0002-9378(00)70517-5.
    1. Miller EM, et al. Field and laboratory methods in human milk research. Am J Hum Biol. 2013;25(1):1–11. doi: 10.1002/ajhb.22334.
    1. Christie WW. A simple procedure for rapid transmethylation of glycerolipids and cholesteryl esters. J Lipid Res. 1982;23(7):1072–1075.
    1. Harris WS, Baack ML. Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity. J Perinatol: official journal of the California Perinatal Association. 2015;35(1):1–7. doi: 10.1038/jp.2014.195.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel