28. Supplementary feeding versus no supplementary feeding (control, placebo, standard care, dietary advice), outcome: adverse events.

Review	Target group	Intervention	Outcome	Assumed risk with comparator	Corresponding risk with intervention	Relative effect (95% CI)	Number of participants (studies)	Certainty of evidence (GRADE)a
Grobler 2013	Adults with HIV	Specific (OKG)b	GI adverse events	542 per 1000	864 per 1000	RR 1.59 (1.06 to 2.39)c	46 (1)	NR
Ota 2015	Pregnant women	Balanced	Small‐for‐gestational age	173 per 1000	137 per 1000 (120 to 156)	RR 0.79 (0.69 to 0.90)d	4408 (7)	Moderate
			Preterm birth	112 per 1000	108 per 1000 (90 to 130)	RR 0.96 (0.80 to 1.16)	3384 (5)	Moderate
			Pre‐eclampsia	73 per 1000	108 per 1000 (60 to 195)	RR 1.48 (0.82 to 2.66)	463 (2)	Very low
		High protein	Small‐for‐gestational age	117 per 1000	185 per 1000 (121 to 282)	RR 1.58 (1.03 to 2.41)e	505 (1)	Moderate
			Preterm birth	219 per 1000	249 per 1000 (182 to 341)	RR 1.14 (0.83 to 1.56)	505 (1)	Low
Sguassero 2012	Children < 5 years of age	Balanced	Diarrhoea	—	—	OR 1.04 (0.67 to 1.62)	108 (1)	NR
			Vomiting	—	—	OR 0.89 (0.38 to 2.10)	108 (1)	NR
CI: confidence interval; GI: gastrointestinal; NR: not reported; OKG: ornithine alpha‐ketoglutarate; OR: odds ratio; RR: risk ratio.

^aAs reported in 'Summary of findings' tables.
 ^bMonohydrated L‐ornithine alpha‐ketoglutarate (OKG).
 ^cOKG associated with significantly more people reporting one or more GI adverse events.
 ^dIncidence of small‐for‐gestational age birth significantly reduced in women given balanced energy and protein supplementation (liquid, chocolate‐flavoured supplement; biscuit; milk; supplement with sesame cake, jaggery, oil; fortified food supplement with peanut butter, soy flour, vegetable oil, sugar, micronutrients; supplement with dried skim milk, enriched bread, vegetable oil; oral supplement (beverage)).
 ^eHigh‐protein supplementation associated with a significantly increased risk of small‐for‐gestational age babies (high protein oral supplement (beverage)).

Additional comments

1. Lazzerini 2013 only reported adverse events in relation to lipid‐based nutrient supplements (LNS) versus all blended foods and LNS versus specific blended foods.
2. Grobler 2013 poorly reported adverse effects in the included studies and, in general, they were related to tolerance rather than adverse effects. Keithley 2002 found no significant differences for acceptance and tolerance of the formulas (Ensure plus versus Advera). Rabeneck 1998 noted that one participant discontinued the supplement (lipisorb‐specialised medium chain triglycerides formula) due to nausea and epigastric pain, and one discontinued as he did not like the taste of the supplement.
3. Kristjansson 2015a calculated the net benefit from supplementary feeding for seven studies that provided home‐delivered rations (randomised controlled trials (RCTs): Bhandari 2001; De Romaña 2000; Grantham‐McGregor 1991; Rivera 2004; controlled before‐and‐after studies (CBAs): Lutter 2008; Santos 2005; Tomedi 2012); and three of the day‐care/feeding centre studies (RCTs: Husaini 1991; Pollitt 2000; CBA: Devadas 1971). They found important differences in the number of calories provided by the supplementary food and the number of extra calories that the children actually consumed in addition to their regular food. In the take‐home studies, the net benefit to children was only 36% of the extra calories provide by the supplement. In the day‐care/feeding centres, the net benefit was 85% of the extra calories provided by the supplement.