Siroy Life Sciences has introduced pure DHA drop in India for first time in Indin Pharmaceuticals industry.

1. CME ORGANISED BY SIROY LIFE SCIENCES
Dr Pankaj Garg
Senior Consultant, Department of Neonatology
Institute of Child Health, Sir Ganga Ram Hospital
pankajgarg69@gmail.com, +91-9810146581
23rd June 2016, Hindu Rao Hospital
DELHI, INDIA.
www.siroylifesciences.com

2. Baby Amelia smallest surviving micropremie baby
21 wks 6days weighing 260 gms born on 24th oct 2006
Respiratory
immaturity Infection
Poor
nutrition
stores
High risk of
multiorgan
failure

3. 3

5. 24 weeks; 520 gms
Stayed in NICU for 4
months; photographed at
1.5 years

6. Preterm survivals are
increasing

7.  AAP: As that of fetus
 Weight gain: 18-20 gms/kg/day
 Length: 0.9-1.0cm/week
 Head Size: 0.9-1.0 cm/week

8.  EUGR is a real challenge to tackle
 Clark. 124 American NICUs for 23-34 weeks
 28% for weight
 34% for length
 16% for head circumference
Clark RH. EUGR remains a serious problem in
prematurely born neonates. Pediatrics 111:986-
990

9. • More rapid weight gain associated with earlier age of enteral feeds and
an earlier age at achievement of full enteral feedings
•Ehrenkranz RA et al. Pediatrics 2006; 117(4):1253-1261

10.  Morbidities
 Sepsis, NEC, BPD
 Poor nutrition
 Emotional deprivation
 Lack of stimulation

11.  Aggressive >>>>>>> Optimal Nutrition
 Parentral nutrition. (SenterreT, Rigo J. J Pediatr
Gastro Nutr 2011; 53: 536-542)
 Enteral nutrition. (Ehrenkranz)
 Decrease the incidence of Sepsis
 PN usage ∞ Sepsis
▪ Centralized pharmacy >> Laminar flow usage >> Isolated
designated place of preparation under aseptic conditions
▪ Use of on line filters ?????
 EN usage decreases sepsis

12.  Preterm babies survival should
be matched with optimum
growth and nutrition is a key
issue there.

13.  Hemodynamically Stable preterm <1250 gms,
<30 weeks
 Bridging PN + MEN >>>Total EN
 Hemodynamically stable >1250 gms, >30
weeks
 Total EN
 Hemodynamically unstable/ NEC/Abdominal
surgical anomalies
 TPN
▪ Look out forTPN associated complications

14.  Calories: 90-110 Kcal/kg/d
 Glucose: 8-12 mg/kg/mt (higher glucose leads to hepatic steatosis);
Insulin use associated with hypoglycemia and associated morbidity;
blood sugar once a shift
 AA: start 3gms/kg/d >>> 3.5-4.0gm/kg/d; no routine tests
 Lipid: start 2gms/kg/d >>> 3-4gm/kg/d; triglyceride biweekly
 Use High Omega 3 containing preparation
▪ Less Cholestasis, Less sepsis, Less BPD
 Multivitamin: Adult MVI: 1cc/kg
 Trace elements: usually after 2 weeks ofTPN
 Electrolytes: Na/K: 2-3meq/kg/d; monitor more frequently
 Calcium / Glycerophosphate

15.  Solutions are always hypertonic and hyperosmolar
 Extravasation
 Usually peripheral suffice
 Can administer fluids with upper limit of osmolarity 800-
1200 mosm/l >>> till 12.5% gucose with AA or 15 %
glucose alone. (low quality evidence)
 Addition of lipids reduce the associated phlebitis

16.  Positive nitrogen balance>>> High quality
evidence
 Weight gain >>> High quality evidence
 Neurocognitive benefits>>>> low quality
evidence

17.  For PN: no routine monitoring; principles
same
 MEN

18.  Milk volume up to 24ml/kg/day introduced
before 96 hours and continued for at least 7
days; n = 754
 NEC RR 1.07 (0.67-1.7), not affected feeding
intolerance or growth rates
Cochrane Database Syst Rev. 2013 Mar 28;3:CD000504.
Early trophic feeding versus enteral fasting for very preterm or
very low birth weight infants.
Morgan J1, Bombell S, McGuire W.

19.  Likely to have had mesenteric ischemia in utero.
 Have an increased risk of Confirmed NEC (6.9, 95% CI
2.3-20)
 ADEPT trial : Preterm infants <35 wks, SGA with abn
doppler flows fed on Day 2 of life achieved full feeds
earlier (18 vs 21 days) than those commenced on Day
6, with no difference in the incidence of NEC (8%) or
sepsis
Leaf. 2012. Pediatrics 129:e 1260-e1268.

20.  Antenatal visit by lactation consultant
 Oropharyngeal colostrum
 EBM expression with in one hour
 Total feeds on D1: 80ml/kg/d
 Orogastric; intermittent bolus over 15 minutes 3
hourly feeds
 Preferably EBM; once 25 ml EBM available add HMF
 Upper acceptable osmolarity 400 mosm/l
 Increase feeds by 30 ml/kg/day till 150-180 ml/kg/day
 Monitor growth
 KMC

24.  Systematic review of ten randomized controlled
trials (more than 600 infants with birth weight
less than 1850 g)
 Small but statistically significant short-term
improvements in weight gain (+2.33 g/kg/d; 95%CI
1.73, 2.93), linear growth (+0.12 cm/week; 95%CI 0.07,
0.18), and head growth (+0.12 cm/week; 95%CI 0.07,
0.16)
Kuschel CA, Harding JE. Multicomponent fortified human milk for promoting
growth in preterm infants (Cochrane Review).Cochrane Library 2004;3

25.  KMC as soon as possible, at least 2 hours / day
 33-34 weeks>> transition to direct breast feeds
 If direct breast fed: stop HMF; add Ca/P;
Vitamin D 800IU/d, Iron, DHA, Zinc
 If breast milk fed: Continue HMF;Vit D 400 IU/d,
DHA

26. Different protocols in different units
• 1800-2200 gm
• Discharge
• Depending on PMA

27.  <33 weeks>> Fenton 2013, neonatal
anthropometric data, 40 lac preterm
neonates, sex and age specific, 22-50 weeks
 >33 weeks>> Intergrowth 21st Century charts,
prescriptive, separate sex

31.  Early stimulation from NICU
 Humanized NICU care
 Regular check up with Developmental
Pediatrician
 DASII

32. Nutrient ESPGHAN 2010 (/KG/D) KOLETZKO 2014 (/KG/D)
<1800 GMS <1500 GMS0
FLUIDS 135-200 135-200
PROTEIN 4-4.5G (<1KG); 3.5-4 G (1-1.8) 3.5-4.5
DHA 12-30 mg 55-60mg
POTASSIUM 66-132mg 78-195mg
CALCIUM 120-140 mg 120-200 mg
PHOSPHATE 60-90 mg 60-140 mg
IRON 2-3 MG 2-3 mg
ZINC 1.1-2 mg 1.4-2.5mg
VIT D 800-1000 IU 400-1000 IU

33.  An Essential fatty acid
 Linoleic acid (LA) 18 carbon: 2 n-6
▪ α Linoleic acid (ALA) 18 carbon: 3 n-3
Desaturation & chain elongation in liver
Docosahexaenoic acid( DHA)
22 carbon: 6 n-3
Eicosapentaenoic acid (EPA)
20 carbon: 5 n-3
Arachidonic acid(AA)
20 carbon: 4 n-6
LCPUFA

34. EFA & LC-PUFA Sources
Omega-6
Class FA
Omega-3
Class FA
Plant seeds
Meat, eggs
Soybean, canola
oil, Walnuts
Fish, sea foods

35. Omega 3 fatty acids Omega 6 fatty acids
Fish / Fish oil Sunflower
Rapeseed or canola Safflower
Peanut Sesame
Olive Palmolive
Perilla Corn
Walnut Primrose
Soya Borage
Green leafy vegetables, dry fruits Invisible fats
Flaxseed or linseed

36. Source Saturates Mono Poly N6 N3 Chol.
mg
Milk fat 62.5 28.8 3.75 26 1.6 274
Dalda 25 45 26 3 1.6 0
Corn 13 24 59 58 0 0
Sunflower 10 19 66 66 0 0
Soya 15 43 38 35 2.6 0
Olive 14 74 8 8 0.6 0
Canola 7 59 30 20 9.3 0
Mustard 12 60 21 15 6 0

37. Ideal diet 5-10:1
Indian Diet 30-70:1
USA 12:1
Japan 2:1

38.  Goyens et at : ALA>> DHA 0.013%
 Goyens PL, Spilker ME, Zock PL, Katan MB, Mensink RP. Compartmental modeling to quantify
alpha-linolenic acid conversion after longer term intake of multiple tracer boluses. J Lipid
Res. 2005;46:1474–83.
 Hussein et al: ALA>> DHA 0.01%
 Hussein N, Ah-Sing E,Wilkinson P, Leach C, Griffin BA, Millward DJ.Long-chain conversion of
[13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in
men. J Lipid Res. 2005;46:269–80.

39.  Part of phospholipid membrane of
 Brain cells; Signal transduction,
neurotransmission and neurogenesis
 Retina
 Anti inflammatory
 Role in atopy, asthma, allergy disorders

40.  Fetal life: uterine accretion of 42-75mg/day; 80%
absorbed in the intestine = 65mg/day = 1-1.5
wt:wt% of Fas in human milk or formula
 Brain development
 Retina development
 Preterm
 Neurodevelopment
 BPD / NEC/ ROP
 Term
 Brain function
 Atopy prevention and treatment

41. Adapted from
Martinez M. J
Pediatr.
1992;120(suppl):S1
29-S138.
Omega-3LCPUFA(mcmolinforebrain)
Age (months)
DHA
DPA
EPA
Placenta
Diet and
Synthesis
DPA
DHA
EPA
0
2000
4000
6000
8000
10000
12000
-3.5 0 6 12 18 24
DHA

42. DHA in Pregnancy & Lactation
Conclusions & Recommendations
Demand for DHA is increased during pregnancy
& lactation
Increased supply of DHA 
beneficial effect on fetus
Consensus recommendation
-Pregnant & lactating women should aim to
achieve an avarage intake of at least
200 mg DHA per day
Koletzko B, et al. World Association of Perinatal Medicine Dietary Guidelines Working
Group. J Perinat Med. 2008;36(1):5-14.

43.  During pregnancy and lactation
 At least 2.6 gms of Omega 3 LCPUFA
▪ 100-300 mg DHA/Day

44. Mean (standard deviation ) intake of total fat LA ,ALA and DHA intake in
pregnant and lactating women
Countries Group total fat Intake (% E) LA Intake (%E) ALA Intake (%E)
DHA Intake (MG)
Recommended FAO(2010) 20-35%E 2-3%E >0.5%E 200mg
Bangladesh (Yakes 2010) Lactating Women 7.6(4.4-11.8)%E 1.9(0.9-3.5)%E 0.3(0.1-0.5)%E
30(10-50)mg
India (N=Muthayya et al.2009a) Pregnant women 24.3%E 6.1(4.7-8.11)%E 0.24(0.2-0.3)%E
11(4-19)mg
(3rd trimester)

45. Reference N Supplementation to mothers Functional measurements: outcomes comments
Cross sectional studies India 676 birth weight No significant fish consumption
(Muthayya et al.2009a) association between above the
DHA status of mother median was 9g
with birth weight . Day .
Women not consuming
fish had a higher risk of
LBW infant compared to
women consuming >median
in third trimester

46. Reference Location N Supplementation to mothers Functional measurements: outcomes comments
Period Dose day age at assessment
Cross sectional studies Cuba 56 amount of EFA in visual acuity:2months no associations
breast milk(ALA=0.92% between infant or
and DHA=0.43%) maternal FA status
and
visual acuity.
Tinoco et al.2009 Brazil 37 (pre-term until 6 months Height (cm) Totaln-3 PUFA
infants) of gestational weight (g) and was positively
associated
age head circumference(cm) with weight gain
(p=0.05)
height(P+0.04) and body
mass index of children
(P=0.05)

47. Study Type and
number
Intervention/
Control
Outcome and Results
Intervention vs Placebo
O'Connor DL, et al. Ross Preterm
Lipid Study. Pediatrics. 2001
;108:359-71
470 prematures
750-1800gr
AA+DHA vs. control
0.26%/ 0.16%
MacArthur Communicative Development, visual
acuity, Bayley motor development were better
Bayley Mental Development Index at 12 mo was
not different
Innis SM, et al. J Pediatr. 2002
May;140(5):547-54.
DBPC
194 prematures
0.15% energy DHA, or
0.14% DHA + 0.27%
ARA or control 28 days
No effect on subsequent visual acuity
Enhances weight gain
Koletzko B, et al. Eur J Nutr. 2003
Oct;42(5):243-53.
49 prematures DHA vs breast milk Growth and milk tolerance not different
Clandinin MT, et al. J Pediatr.
2005;146:461-8.
361 preterm infants DHA vs control for 96
weeks
Supplemented groups had higher Bayley mental and
psychomotor development scores at 118 weeks and
better growth
Smithers LG, et al. Prostaglandins
Leuk EFA 2008;79:141-6. DINO
trial
DBPC
preterm
1% DHA vs 0.3% DHA high-DHA group exhibited an acuity that was higher
than the control group
Makrides M, et al. JAMA.
2009;301:175-82.
RDBP
657 Prematures less
33 weeks
1% DHA vs 0.3% DHA Bayley MDI was higher in girls
Bayley MDI was higher also in infants born
weighing less than 1250 g but NS
Smithers LG, et al. Am J Clin
Nutr. 2010;91:628-34.
DINO trial 1% DHA vs 0.3% DHA 3 times the standard amount of DHA did not result in any
clinically meaningful change to language development
or behavior at 3 to 5 years
LC-PUFA in Preterm Infant Formula

50. Countries Age Group total fat Intake (% E) LA Intake (%E) ALA Intake (%E)
DHA Intake (MG)
IOM (Institute of Medicine )2005 1-3yrs 30-40% 5-10%E 0.6-12%E
4-18yrs 25-35% 5-10% 0.6-12%E
FAO 2010 6-24 months At least 35% 3-4.5%E 0.4-0.6%E 100mg(age2-
4yrs)
Bangladesh (Yakes 2010) Breastfed (24-35months) 19.5(10.5-30.1)%E 3.5(1.7-6.3)%E 0.39(0.19-0.68)%E 40(10-80)mg
Non Breastfed (24-35months) 12.7(6.2-21.5)%E 2.9(1.3-5.2)%E 0.42(0.12-0.74)%E 10(0-30)mg
Non Breastfed ( 36-48 months) 15.6(7.8-26.9)%E 3.1(1.3-5.8)%E 0.41(0.18-0.76)%E 20(10-30)mg
Gambia(Prentice & Paul) 0-6 months 46.2%E 6.0%E 0.38%E
108mg
7-12 months 34.4%E 5.4%E 0.28%E 87mg
12-17 months 27.5%E 5.1%E 0.23%E 75mg

51. Reference Location N Subject Supplementation to mothers Functional measurements: outcomes
comments
period Dose (% of total fatty acids ) age at assessment
Cross sectional studies China 245 Term Infant Birth until F1:0.18% AA+0.18% DHA BSID:3-6months no
significant mixed feeding
Randomized controlled 6 months F2:no LCPUFA differences for breast milk+
Trials (Ben et al.2004) F3: Breast milk growth between supplemented
F4: Breast Milk +F1 the four feeding formula group
groups.
Showed best
growth in the
first 3
months
(EL-Khayat et al 2007) Pakistan 42+15 PEM infants 8 weeks PUFA supplemented Mental development Positive
correlations
control healthy index (MDI), PDI between
plasma
children of BSID-II AA and DHA
levels
and both MDI and
PDI
Unay et al 2004 Turkey 80 Healthy Infants Birth to 16wks DHA BERA Positive : more

52.  2-6 weeks of age.
 2-3 mg/kg/day
 AAP guidelines / ESPGHAN guidelines

53. A.LSRO 2002.
B.Tsang et al 2005.
C. ESPGHAN 2010.
D. Koletzko, Pointdexter, Uauy 2014.
References

54. Inadequate
nutrition
Postnatal
Growth failure
Impaired
neurocognitive
development
Ziegler J Ped Gastro/Nutr 2007

55. Aggressive
nutrition saves
preterm babies
and their brain

56.  Siroy DHA drop (Pure DHA 100mg/ml) in 30 ml bottle
 D-Bon drop (Vitamin D3 800 IU with DHA 100mg/ml) in 15 ml bottle

57. Dr Pankaj Garg
Senior Consultant, Department of Neonatology
Institute of Child Health
Sir Ganga Ram Hospital
pankajgarg69@gmail.com +91-9810146581
www.siroylifesciences.com