COMPLEMENTARY FEEDING WITH FORTIFIED SPREAD IS LIKELY TO REDUCE THE INCIDENCE OF SEVERE STUNTING AMONG 6–18 MONTH OLD RURAL MALAWIAN INFANTS

Abstract

Objective

To compare growth and incidence of malnutrition among infants receiving long-term dietary complementation with ready-to-use fortified spread (FS) or micronutrient fortified maize-soy flour (LP).

Design

Randomized, controlled, single-blind trial

Setting

Rural Malawian population with high incidence of malnutrition

Participants

182 six-month-old infants.

Intervention

Participants were randomized to receive 1-year-long daily supplementation with either 71g of LP (282 kcal energy / day), 50g FS50 (256 kcal), or 25g FS25 (127 kcal).

Main outcome measures

Weight and length gain, incidence of severe stunting, underweight, and wasting.

Results

The mean weight and length gains in LP, FS50 and FS25 groups were 2.37, 2.47, and 2.37 kg (p= 0.658) and 12.7, 13.5, and 13.2 cm (p=0.234), respectively. In the same groups, cumulative 12-month incidence of severe stunting was 14.0%, 0.0% and 4.0% (p=0.011), severe underweight 15.0%, 22.5% and 16.9% (p=0.706), and severe wasting 1.8%, 1.9% and 1.8% (p=0.999). Compared to LP-supplemented infants, those given FS50 gained on average (95%CI;p) 100 g (−143 to 343; p=0.419) more weight and 0.8 cm (−0.1 to 1.7; p=0.091) more length. There was a significant interaction between baseline length and intervention (p=0.042); among children with below-median length at enrolment, those given FS50 gained on average 1.9 cm (0.3 to 3.5; p=0.020) more than individuals receiving LP.

Conclusions

One-year-long complementary feeding with FS does not have significantly larger effect than maize-soy flour on the average weight gain of all infants, but it seems to boost linear growth in the disadvantaged individuals and hence decrease the incidence of severe stunting.

INTRODUCTION

In Malawi, like most developing countries, childhood under-nutrition is a serious problem. Between 30 to 50% of Malawian children are undernourished by the age of 18 months.¹ The period of greatest vulnerability is between 6 and 18 months of age.² Apart from causing acute morbidity, serious developmental problems, and other adverse long-term sequelae, under-nutrition is estimated to contribute to approximately half of the worldwide deaths in under-five-year-old children.^3,4

The epidemiology of under-nutrition in Malawi and elsewhere in Sub-Saharan Africa necessitates emphasis on early prevention but there are no easy options for it. Infection control has not proven widely successful, few indigenous foods are rich in all important nutrients or available throughout the year, and poverty limits possibilities for purchasing commercially available nutritious foods.⁵ In Malawi, thin porridge made from micronutrient enriched maize and soy flour is often promoted as the main complementary food for infants and young children. However, it has low energy density and it resembles the staple food in the area, which may result in displacement of habitual foods from the beneficiary’s diet or diversion of the complementary food to other family members.⁶

Recently, Briend and his collaborators developed the concept of highly nutrient and energy dense spreads, which are simple to produce, need no cooking before use, and can be stored for months even in warm conditions.^7,8 The best known formulation of such spreads is called ready-to-use therapeutic food, RUTF.^9,10 Several clinical trials in Malawi have shown that RUTF is safe and effective in the rehabilitation of severely malnourished children, and that a modification of it interferes with habitual diet less than a porridge supplement and has a positive effect on less severely underweight and stunted 3–4-year olds.^6,11–15 Recent data from a preliminary dose-finding trial suggested that home-provision of fortified spread to moderately underweight 6–17-month-old infants improves their nutritional status and results in markedly increased linear growth and improved weight gain.¹⁶

Because of their efficacy in promoting growth among severely or moderately malnourished infants, and their ease of use, simple production, and relatively low price, fortified spreads (FS) might logically also have a potential as complementary foods in the Sub-Saharan setting. To compare the efficacy of FS and a traditionally used complementary food in promoting health and preventing the development of under-nutrition, we conducted a randomized controlled single-blind trial, where initially healthy infants were provided for one year with daily rations of either maize-soy flour or FS. The present communication analyses the hypothesis that infants receiving FS would grow better and be less likely to develop under-nutrition than those receiving maize and soy flour. Morbidity and developmental outcomes will be reported in separate communications.

METHODS

Study area and timing

The study was conducted between October 2004 and December 2005 in Lungwena, a rural Malawian community with high prevalence of early childhood stunting and underweight.^2,17 The staple food, maize, was grown during the single rainy season between December and March. Exclusive breastfeeding for babies was almost non-existent and infant diet was typically complemented with thin maize porridge already from 2–6 months of age.

Eligibility criteria, enrolment, and randomization of the trial participants

Inclusion criteria included age 5.50 months to 6.99 months, residence in the study area, and an informed consent from at least one authorised guardian. Exclusion criteria were low weight-for-height (WHZ <–2.0), presence of edema, history of peanut allergy, severe illness warranting hospitalization on the enrolment day, concurrent participation in another clinical trial, or any symptoms of food intolerance within 30 minutes after the ingestion of a 6 g test dose of FS, one of the food supplements used in the trial.

For enrolment, trained health surveillance assistants contacted all families who were known to live in the area and have a baby of approximately right age. Infants were invited to an enrolment session, where they were screened for eligibility and guardians were given detailed information on the trial contents. Before enrolment, a guardian signed a written consent form for trial participation.

For group allocation, guardians picked one from a set of identically appearing opaque envelopes, each containing a paper indicating an identification number and randomly assigned allocation to one of the three interventions. The randomization list and envelopes were made by people not involved in trial implementation and the code was not disclosed to the researchers or those assessing the outcomes until all data had been entered into a database.

Interventions and follow-up

There were three intervention schemes. Infants in the control group were provided with an average of 71 g / day of micronutrient fortified maize and soy flour (Likuni Phala, LP). Participants in the other two groups received on average either 50 g / day or 25 g / day of micronutrient fortified spread (FS50 or FS25). The supplements were home-delivered at three-weekly intervals (at each food delivery, either three 500 g bags of LP, four 262 g jars of FS50, or two 262 g jars of FS25 were given).

Likuni phala was purchased from a local producer (Rab Processors, Limbe, Malawi). Fortified spread was produced at a Malawian non-governmental organization, Project Peanut Butter (Blantyre, Malawi), from peanut paste, milk powder, vegetable oil, sugar, and premade micronutrient mixture (Nutriset, Malaunay, France). All supplements were fortified with micronutrients, but the level of fortification varied between the products. The difference between the FS50 and FS25 supplementation was in the amount of food base given (50 vs. 25 g / day). The micronutrient content, however, was adjusted so that children in both FS groups received similar daily micronutrient doses. Table 1 shows the energy and nutrient contents of a daily ration of each supplementation scheme.

Table 1.

Energy and nutrient content of the daily ration of the food supplement used in the trial

	Intervention group
Variable	LP	FS50	FS 25
Weight	71 g	50 g	25 g
Energy (kcal)	282	256	127
Protein (g)	10.3	7.0	3.5
Carbohydrates (g)	n/a*	13.8	6.6
Fat (g)	3.1	16.9	8.5
Retinol (µg RE)	138	400	400
Folate (µg)	43	160	160
Niacin (mg)	3	6	6
Panthothenic ac.(mg)	n/a	2	2
Riboflavin (mg)	0.3	0.5	0.5
Thiamin (mg)	0.1	0.5	0.5
Vitamin B6 (mg)	0.3	0.5	0.5
Vitamin B12 (µg)	0.9	0.9	0.9
Vitamin C (mg)	48	30	30
Vitamin D (µg)	n/a	5	5
Calcium (mg)	71	366	283
Copper (mg)	n/a	0.4	0.4
Iodine (µg)	n/a	135	135
Iron (mg)	5	8	8
Magnesium (mg)	n/a	60	60
Selenium (µg)	n/a	17	17
Zinc (mg)	3.6	8.4	8.4

^*n/a = information not available

FS50 and FS 25 could be eaten as such, whereas the maize-soy flour (LP) required cooking into porridge before consumption. The guardians were provided with spoons and advised to daily offer their infants either porridge containing 12 spoonfuls of maize-soy flour (LP group), 8 spoonfuls of fortified spread FS50, or 4 spoonfuls of fortified spread FS25, divided onto 2–3 daily doses. All mothers were encouraged to continue breastfeeding on demand and to feed their infants only as much of the food supplement as the infant wanted to consume at a time.

The participants were visited weekly at their homes, to collect information on supplement use and possible adverse events. Empty food containers were collected every three weeks. At 17, 34, and 52 weeks after enrolment, the participants underwent a physical examination, anthropometric assessment and laboratory tests.

Measurement of outcome variables

The primary outcome was weight gain during the 12-month follow-up. Secondary outcomes included length gain, mean change in anthropometric indexes weight for age (WAZ), length for age (LAZ), and weight for length (WLZ), incidence of severe or moderate underweight, stunting or wasting (WAZ, LAZ, and WLZ below –3 or –2, respectively), change in head or mid upper arm circumference, and change in blood haemoglobin and serum ferritin concentration.

Weight was measured from naked infants with electronic infant weighing scale (SECA 834, Chasmors Ltd, UK) and recorded to the nearest 10g. Length was measured to the nearest 1 mm with a high quality length board (Kiddimetre, Raven Equipment Ltd, Essex, UK). Mid upper arm circumference (MUAC) and head circumference were measured with non-stretchable plastic tapes (Lasso-o tape, Harlow Printing Limited, South Shields, Tyne & Wear, UK). Anthropometric indices (WAZ, LAZ, WLZ) were calculated with Epi-Info 3.3.2 software (CDC, Atlanta, USA), based on the CDC 2000 growth reference.¹⁸

A 2 ml venous blood sample was drawn and serum separated by centrifugation at the beginning and end of follow-up. Haemoglobin concentration was measured from a fresh blood drop with Hemo-Cue® cuevettes and reader (HemoCue AB, Angelholm, Sweden). Serum ferritin concentration was analysed from frozen sera with commercial test kits according to the manufacturer’s instructions (Ramco Laboratories, Stafford, Texas, USA).

Thick and thin blood smears were made, stained with Giemsa, and screened microscopically for malaria parasites from symptomatic participants at enrolment. Screening for human immunodeficiency virus infection was done from fresh blood with two antibody rapid tests and positive results were confirmed with DNA amplification technology, according to the manufacturers’ instructions (Determine, Abbot Laboratories, Abbot Park, USA, Uni-Gold, Trinity Biotech plc, Bray, Ireland, Amplicor HIV-1 Monitor Test Version 1.5, Hoffmann-La Roche, Ltd, Basel, Switzerland).

Data Management and analysis

Collected data were recorded on paper forms, transcribed to paper case report forms (CRF) and double-entered into a tailor made Microsoft Access 2003 database. The two entries were electronically compared and extreme or otherwise susceptible values were confirmed or corrected.

Statistical analysis was carried out using Stata 9.0 (StataCorp, College Station, USA) on an intention-to-treat basis. Infants with no anthropometric data after enrolment were excluded from outcome analyses but included in the comparison of baseline characteristics. The main analyses on anthropometric measures used data from all the 176 analyzable children, either using the last values carried forward (and back-transform WAZ and HAZ at 18 months to kg and cm for metric presentation) for the eight children who dropped out early, or using survival analysis method to deal with censoring. Sensitivity analysis limited to the 168 children with complete data gave similar findings (details not shown).

For continuous and categorical outcomes, the three intervention groups were compared with analysis of variance (ANOVA) and Fisher’s exact test, respectively. Survival analysis was used to determine cumulative probability of severe or moderate malnutrition among different groups, and the difference were tested by the log-rank test. An event was considered to have happened at mid-point between the time the event was detected and the previous measurement. Individuals with a particular form of malnutrition already at enrolment were excluded from survival analyses concerning the incidence of that outcome. For the studies of compliance using visits as units of analysis, the Huber-White robust standard error was used to allow for correlated data (multiple visits per child).

Ethics, study registration and participant safety

The trial was performed according to Good Clinical Practice guidelines (ICH-GCP) and it adhered to the principles of Helsinki declaration and regulatory guidelines in Malawi. Before the onset of enrolment, the trial protocol was reviewed and approved by the College of Medicine Research and Ethics Committee (University of Malawi) and the Ethical Committee of Pirkanmaa Hospital District (Finland). Key details of the protocol were published at the clinical trial registry of the National Library of Medicine, Bethesda, Md, USA (http://www.clinicaltrials.gov, trial identification is NCT00131209).

A data safety and monitoring board continuously monitored the incidence of suspected serious adverse events (SAE), defined as any untoward medical occurrence that either resulted in death or was life-threatening or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant disability / incapacity or other serious medical condition.

RESULTS

Of the 303 initially screened infants, 65 were too old (> 6.99 months), 2 were too young (<5.5 months) and 2 were too ill on the day of screening or enrolment. Among the rest, 49 were not brought to the enrolment session (3 died, 16 moved away, 7 not interested, 22 no explanation given), and 3 declined participation after receiving full information of the trial. The remaining 182 infants were randomized into three intervention groups (Figure 1). None of the eligible participants who received the 6g test dose was allergic to FS.

Figure 1.

Flow of participants

Table 2 shows the baseline characteristics of the participants by intervention group. At enrolment, mean anthropometric measurements were comparable in the LP and FS50 groups, whereas infants in the FS25 group were on average 250 and 380 g heavier than the FS50 and LP groups respectively (table 2). They were also 0.3 and 0.7 cm longer than infants in the other two groups. No participant was severely wasted at beginning; the prevalence (number of infants) of severe underweight in the LP, FS50, and FS25, groups was 1.6% (1), 3.3% (2), and 0.0% (0), and that of severe stunting 3.3% (2), 6.6% (4), and 1.7% (1), respectively. Nine of the participants had a positive HIV-antibody test at enrolment, but only one of them was truly HIV infected, as evidenced by a positive PCR test.

Table 2.

Background characteristics of the participants at enrolment

Variable	LP	FS50	FS 25
Number of participants	61	61	60
Number of boys (%)	24/61 (39.3%)	33/61 (54.1%)	34/60 (56.7%)
Number with PCR confirmed HIV infection (%)	0/55 (0.0%)	0/55 (0.0%)	1/55 (1.8%)
Number with HIV antibodies (%)	3/55 (5.5%)	2/55 (3.6%)	4/55 (7.3%)
Proportion with clinical malaria*	1/61 (1.6%)	1/61 (1.6%)	2/60 (3.3%)
Mean (SD) number of below 5 year old children per participant household	2 (0.9)	2 (0.8)	2 (0.9)
Mean (SD) age months	5.91 (0.41)	5.93 (0.44)	5.89 (0.36)
Mean (SD) weight (kg)	6.92 (0.93)	7.05 (0.90)	7.30 (0.92)
Mean (SD) length (cm)	62.8 (2.1)	63.2 (2.6)	63.5 (2.4)
Mean (SD) mid upper arm circumference (cm)	13.4 (0.9)	13.5 (1.1)	13.9 (1.1)
Mean (SD) head circumference (cm)	43.0 (1.5)	43.1 (1.7)	43.2 (1.3)
Mean (SD) weight-for-age Z score (WAZ)	−0.65 (1.07)	−0.62 (1.04)	−0.33 (0.94)
Mean (SD) length-for-age Z score (LAZ)	−1.20 (0.82)	−1.20 (1.01)	−1.00 (0.77)
Mean (SD) weight-for-length Z score (WLZ)	0.48 (1.08)	0.55 (0.90)	0.75 (0.86)
Mean (SD) blood haemoglobin concentration (g/l)	114 (16)	106 (17)	113 (15)
Mean (SD) serum ferritin concentration (ng/ml)	56.9 (73.6)	45.7 (37.4)	67.2 (74.4)

^*reported fever and observed peripheral b lood malaria parasit aemia

During the 12-month follow-up, ten infants died and four were otherwise lost to follow-up before age 18 months (Figure 1). The success rate of following up to age 18 months was not significantly different between intervention groups (p=0.471; Fisher’s exact test). Only six participants had no anthropometric data at all after enrolment and there was no difference in this between intervention group (p=0.702; Fisher’s exact test).

The assumed causes for the 10 deaths were diarrhoea, malaria and drowning (LP group), diarrhoea, meningitis, malaria and poisoning (FS50 group), and respiratory tract infection and malaria (FS25 group).

All mothers reported that their infants readily ate the provided supplement and diversion of any portion to someone else than the intended beneficiary was reported only at 4/8864 (0.05%) food delivery interviews, 3 in the LP and 1 in the FS50 group. From the 3-weekly home visits during which leftover trial products were checked, the percentage of visits with leftovers found were 2.8%, 9.8% and 5.6% in the LP, FS50, and FS25 groups respectively (P<0.001).

Among the 176 participants, mean gains in weight and length were 100 g (95% CI –143 to 343 g) and 0.8 cm (–0.1 to 1.7 cm) higher in the FS50 than the LP group. Correspondingly, mean decreases in weight-for-age (WAZ) or length-for-age (LAZ) were smaller among the FS50 than the FS25 or LP infants and there was also a smaller drop in blood haemoglobin concentration in the FS50 group. None of the differences, however, reached statistical significance (table 3).

Table 3.

Outcome changes among infants receiving different doses of fortified spread (FS) and Likuni phala (LP) up to 12 months follow-up

Variable	LP	FS50	FS 25	p-value1
Mean (SD) change in weight (kg)	2.37 (0.60)	2.47 (0.77)	2.37 (0.61)	0.66
Mean (SD) change in length (cm)	12.7 (1.7)	13.5 (2.9)	13.2 (2.9)	0.23
Mean (SD) change in mid upper arm circumference (cm)	1.1 (0.9)	1.0 (1.1)	1.0 (0.8)	0.64
Mean (SD) change in head circumference (cm)	3.7 (0.5)	3.7 (0.8)	3.7 (0.6)	0.96
Mean (SD) change in weight-for-age Z score (WAZ)	−1.29 (0.63)	−1.18 (0.90)	−1.32 (0.65)	0.53
Mean (SD) change in length-for-age Z score (LAZ)	−0.74 (0.95)	−0.59 (1.22)	−0.64 (0.86)	0.71
Mean (SD) change in weight-for-length Z score (WLZ)	−0.98 (0.83)	−1.05 (0.86)	−1.13 (0.75)	0.62
Mean (SD) change in blood haemoglobin concentration (g/l)	−6.8 (20.6)	−0.4 (22.1)	−3.8 (18.2)	0.28
Mean (SD) change in serum ferritin concentration (ng/ml)	16.2 (116.4)	11.5 (61.2)	−0.7 (172.4)	0.83

¹Analysis of variance (ANOVA)

There was an interaction between intervention group (FS50 vs. LP) and baseline LAZ, both using length gain (p=0.042) or weight gain (p=0.002) as an outcome. Among subjects with baseline LAZ below median in this trial (−1.035), the mean gain in length was 1.9 cm (0.3 to 3.5 cm; p=0.020) or 0.40 z-scores (−0.15 to 0.95 z-score; p=0.150) bigger in the FS50 than in the LP group. Comparable differences in weight gain were 404 g (74 to 735 g; p=0.017) or 0.43 z-scores (0.07 to 0.80 z-score; p=0.020). Among subjects with baseline LAZ above median, the difference in length was −0.4 cm (−1.3 to 0.5 cm, p=0.345) or −0.09 z-score (−0.58 to 0.39 z-score; p=0.706) and that in weight was −254 g (−604 to 96 g, p=0.153) or −0.25 z-score (−0.64 to 0.14 z-score; p=0.211). There was no significant interaction between intervention and baseline WAZ (p=0.137).

As secondary end-points we looked at the proportion of subjects who developed severe or moderate-to-severe underweight, stunting and wasting during the follow-up. The proportion of subjects who developed other forms of malnutrition did not differ markedly between the intervention groups, but severe stunting occurred significantly less frequently in FS50 and FS25 than in LP group (table 4). After enrolment, no infant in FS50 group, 3.5% in FS25, and 12.5% of LP infants developed severe stunting (p=0.008; Fisher’s exact test). The 95% CI for the difference between FS50 and LP was 3.8 to 21.2% (p=0.013).

Table 4.

Proportion of participants developing various forms of under-nutrition during the trial follow-up period

Variable	LP	FS50	FS 25	p-value1
Number (%) ever developed severe stunting (LAZ <−3)	7/56 (12.5)	0/56 (0.0)	2/58 (3.5)	0.008
Number (%) ever developed moderate-to-severe stunting (LAZ <−2)	11/49 (22.5)	10/51 (19.6)	15/55 (27.3)	0.64
Number (%) ever developed severe underweight (WAZ <−3)	8/57 (14.0)	11/58 (19.0)	9/58 (15.5)	0.81
Number (%) ever developed moderate-to-severe underweight (WAZ <−2)	23/53 (43.4)	20/56 (35.7)	20/57 (35.1)	0.62
Number (%) ever developed severe wasting (WHZ <−3)	1/58 (1.7)	1/60 (1.7)	1/58 (1.7%)	1.00
Number (%) ever developed moderate-to-severe wasting (WHZ <−2)	5/58 (8.6)	7/60 (11.7)	3/58 (5.2)	0.47

¹Fisher’s exact test

Cumulative incidence of stunting during the 12-month period was also calculated based on survival analysis methods that dealt with censoring differently from the analysis shown in table 4. This approach confirmed that severe stunting developed less often and later in the FS50 and FS25 than in the LP group (0.0, 4.0 and 14.0% respectively; p=0.011, log-rank test, Figure 2a). The cumulative incidence of moderate-to-severe stunting was similar in the three groups, but infants in the FS50 group developed the condition on average somewhat later. However, the latter result was not statistically significant (p=0.656, log-rank test, Figure 2b).

Figure 2.

Cumulative incidence functions of (a) severe stunting and (b) moderate-to-severe stunting among children in the LP (dotted line), FS25 (broken line) and FS50 (solid line) groups

Calculated from the absolute risk reduction, the number (95%CI) of infants needed to be supplied for one year with FS50 to prevent one case of severe stunting was 8 (5 to 26).

All interventions were well tolerated by the participants. Besides the ten deaths (4, 4 and 2 in LP, FS50 and FS25; figure 1), three other participants (one in each intervention group), were hospitalized and recorded as having experienced a serious adverse event (SAE) during the follow-up. The LP, FS50 and FS25 groups shared 5, 5 and 3 of these SAEs (p=0.819; Fisher’s exact test). Three of the SAEs were considered unrelated and 10 probably unrelated to the trial interventions.

DISCUSSION

The present trial was carried out to test the growth promoting effects of two micronutrient-fortified, energy dense ready to use spreads (FS50 and FS25), when used as complementary foods for 6–18 month old infants in rural Malawi. Enrolment rate for the trial was high, group allocation was random, follow-up was identical for all groups, loss-to-follow-up was very infrequent and people measuring the outcomes were blinded to the group allocation. Hence, the observed results are likely to be unbiased and thus representative of the population from which the sample was drawn.

In our sample, infants receiving FS50 or FS25 for one year gained on average slightly more weight and length than those receiving an approximately iso-energetic portion of maize and soy flour (LP). However, the differences between the groups were modest (mean differences between FS50 and LP groups were 100 g and 0.8 cm) and statistical hypothesis testing could not exclude the possibility of random findings. Therefore, the data do not support our initial hypothesis that 1-year-long complementary provision of FS to all over-six-month infants in rural Malawi would be noticeably better than corn-soy flour in promoting their mean weight or length gain by 18 months of age. Rather, the results seem to be mostly in line with the modest findings from other dietary intervention trials for infants in similar settings, documenting 0–0.6 standard deviations (0 – 400 g or 0–1 cm) higher mean weight or length gains in intervention groups than among unsupplemented controls.^19–24

In contrast to the mean gains, our study demonstrated a marked and statistically significant difference in the incidence of severe stunting between the FS50 and LP groups. Also, a stratified analysis suggested an interaction between initial height and the intervention group, as demonstrated by bigger between-group differences in both length and weight gain among infants with at least mild stunting at enrolment. Caution must be exercised when interpreting these results, as the incidence of severe stunting was only one of several secondary outcomes of the trial and the interaction finding came from a post-hoc exploratory analysis. The results are, however, biologically plausible and there was a trend towards a dose-response. Therefore, we feel that the results from the sample appropriately represent the larger population. Furthermore, the results are consistent with an earlier trial from West Africa, in which supplementation of stunted children with FS induced marked catch-up growth among them.²⁵ Put together, these data suggest that a dietary intervention with FS can boost linear growth and reduce the incidence of the severest forms of stunting especially when directed to initially disadvantaged infants. If the whole unselected infant group needs to be targeted, the intervention should probably also address the other major risk factors for growth failure (e.g. infections and inappropriate child care).²⁶

In our sample, eight infants needed to be supplemented for one year with FS50 to prevent one case of severe stunting. At present, it is difficult to assess the public health impact resulting from such an intervention and the potential reduction of severe stunting. Stunting is associated with various adverse sequelae such as developmental delay, lower work capacity, worse economic status as adult, and delivery problems.²⁷ But it is not known whether these outcomes are particularly associated with any linear growth failure or its’ severest forms. Such associations and the possibility to prevent various health consequences with an FS intervention need to be addressed in later trials. Such studies are further justified by recent evidence from a Ghanaian trial, suggesting that infant motor development can be markedly enhanced in a low-income setting by a 6-month long provision of Nutributter, another lipid-based nutrient supplement. ³⁴

Although we collected information on compliance, it came from parental recollections, which are often unreliable in dietary interventions. Hence, we can not rule out a possibility of food sharing and its potential impact on the results, especially since the two supplement types differed in many ways from each other. In fact, earlier studies from the same research site suggest that both LP and FS are shared within the families but this occurs more often with LP. ^{6, (Valerie Flax and others, in press)} In this respect, our trial thus looked at effectiveness, i.e. infant outcomes after the provision of different food supplements to the family, rather than assessing growth under ideal conditions where participants truly ate all supplements that were intended for them.

Another major limitation of the trial is the lack of a non-supplemented control group, because of which we can only make solid conclusions on the relative value of the FS and maize-soy flour (LP) supplementation, but not on their independent effect. In a previous study, conducted 10 years earlier in the same area, the difference in the 50^th centile weight and length between 6 and 18 months of age was 2.3 kg and 11.9 cm among unsupplemented infants, i.e. 0.1 kg and 0.8 cm less than mean gains for the LP control group in the current trial. ¹⁷ However, the different anthropometrical methodology in the earlier trial and its historical nature limit its use for conclusive comparisons.

At present, the ex-factory price of FS, when made in Malawi, is approximately 4 USD / kg, corresponding to a daily cost of 20 US cents for a 50 g dose. Unsubsidized, this price is presumably unaffordable to many families in rural Malawi. Our own results with FS25, as well as those from a recent Ghana trial²⁴ using a daily dose of 20 g suggest, however, that a lower and markedly cheaper dose may be as efficient in growth and development promotion as the FS50 dose used in the current trial. Other potential means for increased affordability include amendments to the spread recipe (e.g. cheaper protein source) and social marketing, both of which alternatives are currently being tested in the Sub-Saharan African setting.

Taken together, our results suggest that one-year-long complementary feeding with FS does not have markedly larger effect than corn-soy flour supplementation on the average weight gain of all infants, but it seems to boost linear growth in the most disadvantaged individuals and hence decrease the incidence of severe stunting in a population where it is otherwise common. A larger and longer trial is, however, needed to confirm the finding and to look at the effect on other outcomes than growth, to analyze if corn-soy flour supplementation also has some health impact, to see if the growth effect persists beyond the age of 18 months, and to guide policy decisions on the use of spreads or corn-soy flour in malnutrition prevention in Malawi and similar settings. Further studies on the possible mechanism of the growth-promoting effect of FS would also be warranted.