. 2018 Apr 14;14(3):e12602. doi: 10.1111/mcn.12602

Table 1.

Included studies nutrient profile (n = 7)

First author year location/setting study name	Design	Sample N & key descriptions	Exposure & measurement	Outcome/s, reference population & measurement	Key findings	MMAT score (* ^, ^, * ^, ****)a
•Lucas et al., 1992 •UK	•Randomised control trial	•N = 42 •21 Per group dropped to 19 per group by 6 months •Approx. evenly gendered groups •Infants from one postnatal ward of parents already decided to feed formula	•Powdered versus ready to feed formula •Randomised at enrolment within 2 days of birth	•Weight, change in weight, & standardised weight z‐score •Local reference population (Cambridge reference growth centiles) •Directly measured at birth, 1, 2 4, 6, 10, 12, & 26 weeks	•Higher body weight in powdered formula group (non‐significant) •Higher body weight change in powdered formula group (1–6 weeks, 1–12 weeks significant, 1–26 weeks non‐significant) •Powdered formula group standardised weight from 6 to 26 weeks around 0.6 compared with ready to feed group around 0.1	****
•Roche et al., 1993 •Canada	•Nonrandomised control trial	•N = 288 •72 Per group. N = 263 with complete data—uneven between groups •52% Female infants •Infants with family history of atopic disease	•Whey hydrolysate versus soy based formula versus standard cow's milk based, breast fed group. •Allocated formula used from birth to 6 months	•Absolute weight gain & standardised weight percentile •Local reference population (Fels Longitudinal Study using Epi Info program) •Directly measured at birth, 2, 4, & 6 months	•Some small differences in weight between groups •Most infants weights ranged within 5th–95th percentile with all groups similar •Cow's milk based formula fed boys were more likely (p < .025) to be greater than 95th percentile for weight	*
•Koletzko, von Kries, Closa, et al., 2009 •Belgium, Germany, Italy, Poland, & Spain •European childhood obesity trial study	•Randomised control trial	•N = 1,138 Enrolled & randomised; N = 1,090 Commenced allocated formula 540 low protein group; 550 high protein group Final at 24 months after loss to follow & weight or length measures N = 635 (313 low; 322 high), •Approx. evenly gendered groups •Infants of healthy mother and parents already decided to feed formula	•Higher (2.05 g/100 ml then 3.2 g/100 ml) versus lower (1.25 g/100 ml then 1.6 g/100 ml) protein content cow's milk casein predominant formulas (breast fed observation group, not included in N) •Allocated formula commenced at enrolment & randomisation which took place up to infant age of 8 weeks	•Absolute weight gain & standardised weight for length z‐score •WHO (World Health Organisation) multicentre growth reference population (2006) using WHO software •Directly measured at 3, 6, 12, & 24 months	•High protein group had higher weight gain from 3 months through to 24 months (statistically significant) •At 24 months adjusted weight for length z‐scores were 0.20 greater in the high protein group compared to low protein group	**
•Rzehak et al., 2009 •Germany •German infant nutritional intervention study	•Randomised control trial	•N = 2,252 enrolled & randomised, Final after dropouts/non‐compliance n = 1,840 Includes those randomised to 4 different formulas (n = 1, 044) + a breast fed observation group (n = 796). •48% Female infants •Infants with family history of atopic disease	•Partially hydrolysed whey (pHF‐W) versus extensively hydrolysed whey (eHF‐W) versus extensively hydrolysed casein (eHF‐C) versus cow's milk formula (CMF) and breastfed observation group •Allocated formula randomised at birth & commenced any time from birth to 16 weeks	•Absolute BMI (body mass index) change & BMI z‐score •WHO multicentre growth reference population (2006) •Medical records for weight at birth, 4 days, 5 weeks, 3.5, 6.5, 11.5, & 23 months	•eHF‐C group had lower BMI compared with other formula groups (statistically significant) up to Month 11 of life but not beyond.	***
•Mennella et al., 2011 •The United States	•Randomised control trial	•N = 64 enrolled & randomised (CMF 35, PHF 29) final after dropout n = 56 (CMF 32, PHF 24), •50% (CMF); 41.7% (PHF) female •Infants without family history of allergy or atopic all fully formula fed with exception of 3 mixed fed with formula and breast milk	•Extensively protein hydrolysed formula (PHF) versus cow's milk formula (CMF) •Allocated formula randomised & commenced at 0.5 months	•Weight for age z‐score and weight for length z‐score •Standardised using WHO multicentre growth reference population (2006) with Anthro software & CDC (Centers for Disease Control and Prevention) growth reference (2000) with Epi Info software •Directly measured monthly from 0.5 to 7.5 months	•Infants in the CMF group had higher weight for age and length z‐scores (both WHO and CDC) compared with PHF group between 3.5 and 7.5 months (statistically significant)	***
•Almquist‐Tangen et al., 2013 •Sweden	•Prospective, longitudinal, population‐based, birth cohort study	•N = 2,666 At baseline, at 18 months N = 2,241 •At 4 months 21.3% formula fed, 4.3% mixed fed with breast and formula milk	•Use of milk cereal drink (MCD—“gruel”) measured via self‐reported questionnaire at 6 months	•BMI, high BMI defined at above 1 SD in study population •No reference population •Directly measured at 12 & 18 months	•Use of MCD at 6 months associated with higher BMI at 12 &18 months (statistically significant)	****
•Inostroza et al., 2014 •Chile	•Randomised control trial	•N = 172 enrolled & randomised at 3 months (86 experimental formula; 86 control formula) Final at 12 months after loss to follow N = 120 (54 experimental formula; 66 control formula), •47% Female •Infants of overweight mothers only BMI >25 kg/m²	•Low protein with probiotics (experimental formula—protein 1.65 g/100 kcal) versus standard formula (protein 2.7 g/100 kcal) both whey predominant formula (breast fed observation group, not included in N). •Allocated formula commenced at 3 months	•Weight gain per day between 3 and 6 months, weight for age, length & BMI z‐scores •Standardised to WHO multicentre growth reference population (2006) •Directly measured at 3, 4, 6, 9, & 12 months	•Lower weight gain between 3 and 6 months in experimental formula group compared to standard formula group (statistically significant) •At 24 months BMI lower in experimental formula group & breast fed group compared with standard formula group (statically significantly)	**

First author year location/setting study name

Design

Sample N & key descriptions

Exposure & measurement

Outcome/s, reference population & measurement

Key findings

MMAT score (* ^, ** ^, *** ^, ****)a

•Lucas et al., 1992

•UK

•Randomised control trial

•N = 42

•21 Per group dropped to 19 per group by 6 months

•Approx. evenly gendered groups

•Infants from one postnatal ward of parents already decided to feed formula

•Powdered versus ready to feed formula

•Randomised at enrolment within 2 days of birth

•Weight, change in weight, & standardised weight z‐score

•Local reference population (Cambridge reference growth centiles)

•Directly measured at birth, 1, 2 4, 6, 10, 12, & 26 weeks

•Higher body weight in powdered formula group (non‐significant)

•Higher body weight change in powdered formula group (1–6 weeks, 1–12 weeks significant, 1–26 weeks non‐significant)

•Powdered formula group standardised weight from 6 to 26 weeks around 0.6 compared with ready to feed group around 0.1

****

•Roche et al., 1993

•Canada

•Nonrandomised control trial

•N = 288

•72 Per group. N = 263 with complete data—uneven between groups

•52% Female infants

•Infants with family history of atopic disease

•Whey hydrolysate versus soy based formula versus standard cow's milk based, breast fed group.

•Allocated formula used from birth to 6 months

•Absolute weight gain & standardised weight percentile

•Local reference population (Fels Longitudinal Study using Epi Info program)

•Directly measured at birth, 2, 4, & 6 months

•Some small differences in weight between groups

•Most infants weights ranged within 5th–95th percentile with all groups similar

•Cow's milk based formula fed boys were more likely (p < .025) to be greater than 95th percentile for weight

•Koletzko, von Kries, Closa, et al., 2009

•Belgium, Germany, Italy, Poland, & Spain

•European childhood obesity trial study

•Randomised control trial

•N = 1,138 Enrolled & randomised; N = 1,090 Commenced allocated formula

540 low protein group; 550 high protein group

Final at 24 months after loss to follow & weight or length measures N = 635 (313 low; 322 high),

•Approx. evenly gendered groups

•Infants of healthy mother and parents already decided to feed formula

•Higher (2.05 g/100 ml then 3.2 g/100 ml) versus lower (1.25 g/100 ml then 1.6 g/100 ml) protein content cow's milk casein predominant formulas (breast fed observation group, not included in N)

•Allocated formula commenced at enrolment & randomisation which took place up to infant age of 8 weeks

•Absolute weight gain & standardised weight for length z‐score

•WHO (World Health Organisation) multicentre growth reference population (2006) using WHO software

•Directly measured at 3, 6, 12, & 24 months

•High protein group had higher weight gain from 3 months through to 24 months (statistically significant)

•At 24 months adjusted weight for length z‐scores were 0.20 greater in the high protein group compared to low protein group

•Rzehak et al., 2009

•Germany

•German infant nutritional intervention study

•Randomised control trial

•N = 2,252 enrolled & randomised,

Final after dropouts/non‐compliance n = 1,840

Includes those randomised to 4 different formulas (n = 1, 044) + a breast fed observation group (n = 796).

•48% Female infants

•Infants with family history of atopic disease

•Partially hydrolysed whey (pHF‐W) versus extensively hydrolysed whey (eHF‐W) versus extensively hydrolysed casein (eHF‐C) versus cow's milk formula (CMF) and breastfed observation group

•Allocated formula randomised at birth & commenced any time from birth to 16 weeks

•Absolute BMI (body mass index) change & BMI z‐score

•WHO multicentre growth reference population (2006)

•Medical records for weight at birth, 4 days, 5 weeks, 3.5, 6.5, 11.5, & 23 months

•eHF‐C group had lower BMI compared with other formula groups (statistically significant) up to Month 11 of life but not beyond.

***

•Mennella et al., 2011

•The United States

•Randomised control trial

•N = 64 enrolled & randomised (CMF 35, PHF 29) final after dropout n = 56 (CMF 32, PHF 24),

•50% (CMF); 41.7% (PHF) female

•Infants without family history of allergy or atopic all fully formula fed with exception of 3 mixed fed with formula and breast milk

•Extensively protein hydrolysed formula (PHF) versus cow's milk formula (CMF)

•Allocated formula randomised & commenced at 0.5 months

•Weight for age z‐score and weight for length z‐score

•Standardised using WHO multicentre growth reference population (2006) with Anthro software & CDC (Centers for Disease Control and Prevention) growth reference (2000) with Epi Info software

•Directly measured monthly from 0.5 to 7.5 months

•Infants in the CMF group had higher weight for age and length z‐scores (both WHO and CDC) compared with PHF group between 3.5 and 7.5 months (statistically significant)

***

•Almquist‐Tangen et al., 2013

•Sweden

•Prospective, longitudinal, population‐based, birth cohort study

•N = 2,666 At baseline, at 18 months N = 2,241

•At 4 months 21.3% formula fed, 4.3% mixed fed with breast and formula milk

•Use of milk cereal drink (MCD—“gruel”) measured via self‐reported questionnaire at 6 months

•BMI, high BMI defined at above 1 SD in study population

•No reference population

•Directly measured at 12 & 18 months

•Use of MCD at 6 months associated with higher BMI at 12 &18 months (statistically significant)

****

•Inostroza et al., 2014

•Chile

•Randomised control trial

•N = 172 enrolled & randomised at 3 months (86 experimental formula; 86 control formula) Final at 12 months after loss to follow N = 120 (54 experimental formula; 66 control formula),

•47% Female

•Infants of overweight mothers only BMI >25 kg/m²

•Low protein with probiotics (experimental formula—protein 1.65 g/100 kcal) versus standard formula (protein 2.7 g/100 kcal) both whey predominant formula (breast fed observation group, not included in N).

•Allocated formula commenced at 3 months

•Weight gain per day between 3 and 6 months, weight for age, length & BMI z‐scores

•Standardised to WHO multicentre growth reference population (2006)

•Directly measured at 3, 4, 6, 9, & 12 months

•Lower weight gain between 3 and 6 months in experimental formula group compared to standard formula group (statistically significant)

•At 24 months BMI lower in experimental formula group & breast fed group compared with standard formula group (statically significantly)

The MMAT provides a quality score based on four pertinent criteria for each study design, studies receive one * per each criteria met. Therefore, studies may meet the following:

One criterion.

^**

Two criteria.

^***

Three criteria.

^****

All criteria.