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Experience with Lipid-based Nutrient ... - The iLiNS Project

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<strong>Experience</strong> <strong>with</strong> <strong>Lipid</strong>-<strong>based</strong> <strong>Nutrient</strong><br />

Supplements (LNS) for the prevention of growth<br />

restriction, severe wasting and anemia<br />

Seth Adu-Afarwuah, PhD<br />

<strong>Project</strong> Manager<br />

<strong>iLiNS</strong>, Ghana<br />

University of Ghana, Legon


Background<br />

• High U5 undernutrition in developing countries:<br />

� 32% stunting ( >177 million)<br />

�20% underweight (> 112 million)<br />

�3.5% severely wasted (19 million)<br />

• <strong>Lipid</strong>-<strong>based</strong> nutrient supplements (LNS) first used to<br />

treat severe malnutrition in late 1990s.<br />

• Recent use of LNS includes prevention of malnutrition<br />

and micronutrient deficiencies.<br />

• Review of effects of preventive LNS on linear growth,<br />

severe wasting and anemia is important for guiding<br />

future actions.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

2


Scope of review<br />

• LNS was provided, effect directly compared<br />

• Not for treatment of acute malnutrition<br />

– Individual/mean pre-intervention WLZ/WHZ > 80% of<br />

the NCHS median or > -2 SD.<br />

• At least some participants < 5 y<br />

• Target outcomes were: linear growth, severe<br />

wasting, and anemia<br />

• Studies categorized into: (a)Targeted stunted (LAZ<br />

< -2) chn. (b) Targeted non-stunted (LAZ > - 2) chn.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

3


Assessment of effect of LNS supplementation<br />

• Effect size*= Mean for intervention – Mean for Control<br />

Pooled SD<br />

– Used largest of effect sizes when >1 for linear growth<br />

– Calculated mean (range) <strong>with</strong>in groups of studies (Stunted<br />

children vs. Non stunted children).<br />

• % Point diff. = % for Intervention - % for Control<br />

* Effect size (ES):<br />

� Can be categorized as small (~0.2), medium (~0.5) or large (> ~0.8).<br />

� <strong>The</strong> larger the ES, the larger the difference between Intervention vs Control.<br />

� Positive value indicates intervention group has greater value of the indicator.<br />

� Negative value indicates Control group has greater value of the indicator.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

4


Number of studies included<br />

Number of studies<br />

Targeted stunted children * 4<br />

Targeted non-stunted children † 5<br />

Total 9<br />

No. of countries ‡ 4<br />

* Stunted: Individual/mean pre-intervention length-for-age z score < -2 SD<br />

† Non-stunted: Individual/mean pre-intervention length-for-age z score > -2 SD<br />

‡ Countries: Malawi = 5; Niger = 2; Algeria = 1; Ghana = 1;<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

5


a. Studies that targeted stunted children<br />

Study Nature of intervention Report by investigator<br />

Maleta et<br />

al., 2004 -<br />

Malawi<br />

Kuusipalo<br />

et al.,<br />

2006),<br />

Malawi.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

• Chn 42-60 mo old<br />

• Mean LAZ: -3.2 (0.9) vs -3.0 (0.8)<br />

• RUTF Vs. Maize-Soy mix (500 kcal/d)<br />

• Folllow-up: 4 wk before supplementation,<br />

12 during and 12 after).<br />

• Duration: 28 wk<br />

• Chn 6-17 mo old<br />

• Mean LAZ: -2.4 (0.9) vs -2.3 (1.0).<br />

• Fortified spread (22, 130, 264, 396<br />

kcal/d milk-<strong>based</strong> or 126, 255, 386 kcal/d<br />

soy-<strong>based</strong>) Vs. No supplementation.<br />

• Duration: 12 wk.<br />

• No effect on linear<br />

growth<br />

• Mean length gain<br />

higher for FS ≥ 130<br />

kcal/d.<br />

• Hb ↑ by 10-17g/L.<br />

• Milk-<strong>based</strong> FS 264<br />

kcal/d had greatest<br />

effects<br />

6


a. Studies that targeted stunted children, cont’d<br />

Study Nature of intervention Report by investigator<br />

Lopriore<br />

et al.,<br />

2004,<br />

Algeria<br />

Isanaka<br />

et al.,<br />

2009,<br />

Niger<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

• Saharawi refugee children 36-72 mo<br />

• Mean LAZ range: -2.73 (0.55) to -3.97 (0.70).<br />

• Fortified spread (<strong>with</strong>/ w’out metronidazole)<br />

(~320 kcal/d), Vs Unfortified spread<br />

(<strong>with</strong>/w’out metronidazole), Vs. No<br />

supplementation.<br />

• Duration: 6 mo<br />

• Chn 6-60 mo old in 6 Intervention Vs. 6<br />

Non-intervention Villages<br />

• Mean LAZ: -1.9 (1.3) Vs -2.2 (1.0)<br />

• RUTF (500 kcal/d) for 3 mo Vs No<br />

supplementation. 5 more mo of follow-up<br />

<strong>with</strong> no further supplementation.<br />

• Duration: 8 mo<br />

• Linear growth 30%<br />

faster in FS group at 3<br />

mo than other two<br />

groups<br />

• At 6 mo, Hb ↑ in FS<br />

was ~ 2x those of 2<br />

groups.<br />

• 36% ↓ in incidence<br />

of wasting<br />

- 58% ↓ in incidence<br />

of severe wasting<br />

7


. Studies that targeted non-stunted children<br />

Study Nature of intervention Report by investigator<br />

Phuka<br />

et al.,<br />

2008,<br />

Malawi<br />

Phuka<br />

et al.,<br />

2009,<br />

Malawi<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

• Chn 6 mo old<br />

• Mean LAZ range: -1.00 (0.77) to -1.20 (1.01).<br />

• FS50 Fortified Spread (264 kcal/d) Vs.<br />

FS25 Fortified Spread (130 kcal/d) Vs.<br />

Fortified corn porridge (Likuni Phala, LP)<br />

(282 kcal/d). FS50 had 2x protein, carbo, &<br />

fat as FS25 but same conc. of vit & min.<br />

• Duration: 12 mo.<br />

• Chn. 6 mo old (Phuka et al., 2008)<br />

• FS50 (264 kcal/d) Vs. FS25 (130 kcal/d ) Vs.<br />

Fortified corn porridge for 12 mo. Follow-up<br />

extended by 2 y.<br />

• Duration: 36 mo.<br />

• 9% and 12.5% ↓ in<br />

incidence of severe<br />

stunting in FS25 and<br />

FS50, resp vs LP.<br />

• Chn on FS50, <strong>with</strong><br />

baseline length <<br />

median gained 1.9 cm<br />

more.<br />

• 9.3% and 16% ↓ in<br />

incidence of severe<br />

stunting in FS25 and<br />

FS50, resp.<br />

• Greater diffs. for chn<br />

stunted at baseline<br />

8


. Studies that targeted non-stunted children, cont’d<br />

Author Nature of intervention Report by investigator<br />

Defourny<br />

et al.,<br />

2009,<br />

Niger<br />

Lin et al.,<br />

2008,<br />

Malawi<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

• Blanket distribution of RUF in project<br />

district. Chn 6-36 mo.<br />

• RUF (~250 kcal) as supplement to usual<br />

diet.<br />

• Duration: 6 mo<br />

• Chn 6 mo<br />

• Initial mean LAZ : -1.0 (1.1) vs -1.1 (1.1).<br />

• Fortified spread (eaten alone) Vs. Fish<br />

power + Home prepared corn porridge)<br />

. Energy content: 200 kcal for 6-8 mo,<br />

300 for kcal 9-18 mo.<br />

• Duration: 12 mo<br />

• 85% ↓ in incidence of<br />

severe wasting<br />

(MUAC < 110 cm)<br />

• Linear growth not<br />

affected.<br />

9


. Studies that targeted non-stunted children, cont’d<br />

Study Nature of intervention Report by<br />

investigator<br />

Adu-Afarwuah<br />

et al., 2007;<br />

Adu-Afarwuah<br />

et al., 2008,<br />

Ghana<br />

• 6 mo old<br />

• Mean LAZ range: -0.20 (1.0) to -0.31<br />

(1.1).<br />

• MMN powder (Sprinkles, SP) Vs.<br />

Ghana MMN crushable tablet (Nutritab, NT)<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Vs. LNS (Nutributter , NB) from 6 to<br />

12 mo Vs. Non-Interventn. (NI)<br />

children not randomized at 6 mo were<br />

assessed at 12 mo only.<br />

• Duration: 6 mo<br />

• NB had greater LAZ<br />

than NT and NT+SP<br />

combined<br />

• 22% ↓ in prevalence<br />

of anemia in NB<br />

group vs NI group.<br />

10


Effect of LNS on linear growth: Stunted children<br />

Author Intervention<br />

group (n)<br />

Maleta et<br />

al., 2004<br />

Kuusipalo et<br />

al., 2006<br />

Lopriore et<br />

al., 2004<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Comparison group<br />

(n)<br />

Effect<br />

size (ES)<br />

ES <strong>based</strong><br />

on:<br />

RUTF (30) Maize-Soy mix (31) 0.15 LAZ gain<br />

Fortified spread<br />

(107)<br />

No supplementation<br />

(18)<br />

0.69 Length<br />

gain<br />

Fortified spread Unfortified spread at 0.75 Length<br />

at 3 mo (103) 3 mo (106)<br />

gain<br />

Fortified spread<br />

at 3 mo (103)<br />

Fortified spread<br />

at 6 mo (103)<br />

Fortified spread<br />

at 6 mo (103)<br />

No supplementation<br />

at 3 mo (45)<br />

Unfortified spread at<br />

6 mo (106)<br />

No supplementation<br />

at 6 mo (45)<br />

0.82 “<br />

0.55 “<br />

0.55 “<br />

11


Effect of LNS on linear growth: Stunted children, cont’d<br />

Author Intervention<br />

group (n)<br />

Isanaka et<br />

al., 2009<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Comparison group<br />

(n)<br />

RUTF (894) No supplementation<br />

(816)<br />

Effect<br />

size (ES)<br />

ES <strong>based</strong><br />

on:<br />

0.14 LAZ gain<br />

12


Effect of LNS on linear growth: Non-stunted children<br />

Author Intervention<br />

group (n)<br />

Phuka et<br />

al., 2008<br />

Phuka et<br />

al., 2009<br />

Comparison<br />

group (n)<br />

Effect<br />

size (ES)<br />

ES <strong>based</strong><br />

on:<br />

FS50 (54) LP (57) 0.35 Length gain<br />

FS25 (57) LP (57) 0.22 “<br />

FS50 (46) LP (50) 0.13 LAZ gain<br />

FS25 (53) LP (50) -0.17 Length gain<br />

Lin et al., Fortified spread: 6- Fish Powder: 0 Length gain<br />

2008<br />

12 mo (125) 6-12 mo (115)<br />

Adu-<br />

Afarwuah et<br />

al., 2007),<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Fortified spread:<br />

12-18 mo (125)<br />

Fish Powder:<br />

12-18 mo (115)<br />

-0.07 Length gain<br />

Nutributter (97) Non-interv. ( 81) 0.26 LAZ Attained<br />

Nutributter (97) Sprinkles (96) 0.40 Length gain<br />

Nutributter (97) Nutritab (101) 0.50 Length gain<br />

13


Effect size for linear growth<br />

1.05<br />

0.8<br />

0.55<br />

0.3<br />

0.05<br />

-0.2<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Effect of preventive LNS on linear growth:<br />

Overall effect size*<br />

0.82<br />

0.52 0.50<br />

0.14<br />

0.18<br />

-0.17<br />

Max Min Mean<br />

Stunted Non-stunted All<br />

Target for intervention<br />

0.82<br />

0.33<br />

-0.17<br />

* Results of 4 studies on stunted children and 5 on non-stunted children<br />

14


Effect of LNS on severe wasting: Stunted children<br />

Author Intervention<br />

group (n)<br />

Isanaka et<br />

al., 2009<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

RUTF<br />

(894)<br />

Comparison group<br />

(n)<br />

No supplementation<br />

(816)<br />

Indicator Difference<br />

Incidence of<br />

WLZ < -3<br />

- 58%<br />

15


Effect of LNS on severe wasting: Non-stunted children<br />

Author Intervention<br />

group (n)<br />

Phuka et<br />

al., 2008<br />

Defourny et<br />

al., 2009)<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Comparison<br />

group (n)<br />

Indicator Difference<br />

FS50 (54) LP (57) % of chn 0<br />

FS25 (57) LP (57) <strong>with</strong> WLZ < -3 0<br />

Fortified spread<br />

(~60,000)<br />

Baseline<br />

(~60,000)<br />

Incidence of<br />

MUAC


Effect of LNS on Hb conc. and anemia: Stunted children<br />

Author Intervention<br />

group (n)<br />

Kuusipalo<br />

et al., 2006<br />

Lopriore et<br />

al., 2004<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Fortified spread<br />

(107)<br />

Fortified spread<br />

at 6 mo (103)<br />

Comparison group<br />

(n)<br />

No supplementation<br />

(18)<br />

Unfortified spread at 6<br />

mo (106)<br />

Indicator Difference<br />

Effect size 0.69<br />

Effect size 0.66<br />

Diff in %↓ -50<br />

Fortified spread No supplementation Effect size 0.74<br />

at 6 mo (103) at 6 mo (45) Diff in %↓ -63<br />

17


Effect of LNS on Hb conc. and anemia: Non-stunted children<br />

Author Intervention<br />

group (n)<br />

Phuka et<br />

al., 2008<br />

Adu-<br />

Afarwuah<br />

et al., 2008<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Comparison group<br />

(n)<br />

Indicator Difference<br />

FS50 (54) LP (57) Effect size 0.30<br />

FS25 (57) LP (57) Effect size 0.16<br />

Nutributter (97) Non-interv. ( 81) Effect size 0.59<br />

% diff -22.1<br />

Nutributter (97) Sprinkles (96) Effect size 0.30<br />

% diff -8.2<br />

Nutributter (97) Nutritab (101) Effect size 0.16<br />

% diff -5.5<br />

18


Effect size for change in Hb<br />

Effect of preventive LNS on Hb: Overall effect size*<br />

1<br />

0.75<br />

0.5<br />

0.25<br />

0<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

0.74<br />

0.69<br />

0.65 0.59<br />

0.30<br />

Max Min Mean<br />

Stunted Non-stunted All<br />

0.74<br />

0.45<br />

0.15 0.15<br />

* Results of 2 studies on stunted children and 2 on non-stunted children<br />

19


Summary: Effect on linear growth<br />

� Studies on effects of preventive LNS remain few (n =<br />

9) and have been done in only three countries.<br />

� 5 showed positive effect on linear growth<br />

� 2 showed no effect on linear growth<br />

� 2 did not report on linear growth<br />

�� Effect sizes are generally modest (Mean: 0.33; Range:<br />

-0.17, 0.82).<br />

� Effect sizes (Mean: 0.52; Range: 0.14, 0.82) are larger<br />

for children whose pre-intervention average LAZ was<br />

low (< -2) than those <strong>with</strong> high LAZ.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

20


Summary : Effect on severe wasting<br />

� Only 3 studies (1 involving stunted chn., 2 involving<br />

non-stunted chn.) reported on severe wasting.<br />

�� In 2 of the 3 studies, preventive LNS reduced the<br />

incidence of severe wasting by 58%-85%<br />

compared to no supplementation or baseline.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

21


Summary : Effect on anemia<br />

� Only 4 studies (2 for stunted chn, 2 for non-stunted<br />

chn) reported on hemoglobin (Hb) and anemia.<br />

� Unlike linear growth, Effect Sizes for Hb are larger<br />

(Mean: 0.45; Range: 0.15, 0.74).<br />

�� Like linear growth, Effect Sizes for stunted chn. (Mean:<br />

0.69; Range: 0.65, 0.74) are larger than those for nonstunted<br />

chn. (Mean: 0.30; Range: 0.15, 0.59)<br />

� Preventive LNS was associated <strong>with</strong> 50-63% drop in<br />

anemia among stunted chn, and 6-22% among nonstunted<br />

chn.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

22


5.0<br />

4.0<br />

3.0<br />

2.0<br />

1.0<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

Cost of LNS<br />

0.0<br />

Malawi Ghana Malawi Niger Ghana<br />

(2004) (2008) (2008) (2009) (2010)<br />

USD/kg 3.0 3.5 4.0 4.5 4.0<br />

23


General considerations<br />

� <strong>Nutrient</strong> compositions (and in some cases concentrations) of<br />

LNS have varied widely.<br />

� Energy intake from LNS varied widely<br />

� Some supplementations were probably too short to allow<br />

detectable differences.<br />

�� Effects of LNS could be underestimated due to inability to<br />

include unsupplemented group in some studies.<br />

� At least one study lacked power to detect significant<br />

differences.<br />

� Anthro results are nearly always reported, but only a few<br />

studies actually reported on incidence/ prevalence of severe<br />

wasting<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

24


Overall conclusions<br />

� Preventive LNS has positive effects on linear<br />

growth, severe wasting and anemia that are<br />

stronger than those of many other intervention<br />

strategies.<br />

� Growing cost of LNS may affect large-scale use,<br />

unless new ways of reducing cost can be found.<br />

S Adu-Afarwuah, PhD<br />

October 2010<br />

25


S Adu-Afarwuah, PhD<br />

October 2010<br />

THANK YOU<br />

26

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