Table 2.
Description of the studies investigating the health effects of cow’s milk intake
| Reference | Study design | Sample size/intervention and control group | Location | Duration | Outcome measures/assessment methods | Main results |
|---|---|---|---|---|---|---|
| IDA/Fe status | ||||||
| Capozzi et al. (2010)( 31 ) | Prospective cohort study | 385 E1 (cow’s milk*): 63 E2 (breast-feeding): 102 E3 (follow-on formula): 220† | Italy | 12 months (from birth to 12 months of age) | IDA (Hb<110 g/l & SF<15 ng/ml) | At 8 months: incidence of anaemia 48 % in E1, 39 % in E2, 11 % in E3 (P<0·05) At 12 months: incidence of anaemia 38 % in E1, 36 % in E2, 15 % in E3 (P<0·05) No stat. sign. diff. between E1 and E2 at 8 and 12 months |
| Daly et al. (1996)( 26 ) | RCT | 100 IG (cow’s milk): 50 CG (Fe-supplemented follow-on formula): 50 | UK | 12 months (from 6 to 18 months of age) | IDA (Hb<110 g/l) | At 18 months: frequency of anaemia 33 % in IG v. 2 % in CG (P<0·0001) |
| Fomon et al. (1981)( 30 ) | nRCT | 41‡ IG (cow’s milk): 21 CG (follow-on formula): 20 | USA | 2·8 months (from 3·7 to 6·5 months of age) | Hb levels (g/l) | No stat. sign. diff. between study groups in Hb levels at 3·7 months: IG 123 (sd 9·7) v. CG 125 (sd 10·4) g/l and at 6·5 months: IG 126 (sd 12·0) v. CG 127 (sd 11·3) g/l (P=NR) |
| Gill et al. (1997)( 28 ) | nRCT (only CG were randomized) | 406 IG (cow’s milk): 57 CG1 (Fe-supplemented follow-on formula): 264 CG2 (follow-on formula): 85 | UK and Ireland | 9 months (from 6 to 15 months of age) | IDA (Hb<110 g/l) | At 15 months: proportion of infants with anaemia 33 % in IG, 11 % in CG1, 13 % in CG2 (P=0·004) |
| Lehmann et al. (1992)( 32 ) | Retrospective cohort study | 220 Cow’s milk before 6 months: NR Cow’s milk after 6 months: NR | Canada | Comparison between cow’s milk consumption before and after 6 months of age (age of infants: 10–14 months) | IDA (Hb<110 g/l) | Introduction of cow’s milk before 6 months sign. related to increased risk of anaemia: OR=3·56 (95 % CI 1·07, 11·26) |
| Sadowitz and Oski (1983)( 33 ) | Retrospective cohort study | 122§ Cow’s milk before 6 months: 36 Cow’s milk after 6 months: 86 | USA | Comparison between cow’s milk consumption before and after 6 months of age (age of infants: 9–12 months) | IDA (Hb<110 g/l & SF<12 ng/ml & EP>30 µg/dl & MCV<70 fl) Fe depletion (Hb>110 g/l & SF<12 ng/ml & EP<30 µg/dl & MCV>70 fl) Fe deficiency (Hb>110 g/l & SF<12 ng/ml & EP>30 µg/dl & MCV<70 fl) Fe insufficient=IDA, Fe depletion and Fe deficiency | No sign. diff. in anaemia between groups (5·5 % in infants introduced to cow’s milk before 6 months and 0 % after 6 months (P=NR)) Sign. diff. in Fe-insufficient subjects between groups (47·2 % in infants introduced to cow’s milk before 6 months and 20·1 % after 6 months (P<0·01)) |
| Thorsdottir et al. (2003)( 34 ) & Thorsdottir and Gunnarson (2006)( 35 ) | Prospective cohort study | 138|| Cow’s milk intake <500 g/d: 80 Cow’s milk intake >500 g/d: 17 | Iceland | Average cow’s milk consumption between 9 and 12 months of age | Fe status: Hb levels (g/l), SF (µg/l), MCV (fl), TfR (mg/l) | No stat. sign. diff. in Hb levels between study groups; <500 g/d v. >500 g/d: Hb=114·8 v. 115·8 g/l (P=NS) Stat. sign. diff. in SF, MCV and TfR levels between study groups; <500 g/d v. >500 g/d: SF=20·1 v. 9·7 µg/l (P=0·001); MCV=77·3 v. 73·1 fl (P=0·001) and TfR=7·0 v. 8·2 mg/l (P=0·041) |
| Tunnessen and Oski (1987)( 29 ) | nRCT | 192 IG (cow’s milk): 71 CG (Fe-supplemented follow-on formula): 121 | USA | 6 months (from 6 to 12 months of age) | IDA (Hb<110 g/l) | At 12 months: incidence of anaemia 25 % in IG v. 11 % in CG (P<0·05) |
| Woodruff et al. (1972)( 48 ) | nRCT | 38 IG (cow’s milk): 13 CG (formula): 25 | USA | 10 months (from 2 to 12 months of age) | Hb (g/100 ml), MCV (cu μ) | Stat. sign. lower Hb levels in IG v. CG at 9 and 12 months (P<0·05), no stat. sign. diff. at 3 and 6 months Stat. sign. lower MCV in IG v. CG at 6 months (P<0·01) and 9 months (P<0·05), no stat. sign. diff. at 3 and 12 months |
| T1DM | ||||||
| Bodington et al. (1994)( 42 ) | Case–control study | 393 Cases (T1DM): 209 Controls: 184 | England | NA; introduction of cow’s milk from birth | Diagnosis of T1DM in children under age 15 years | Similar proportion of children were introduced to cow’s milk from birth in cases and controls |
| EURODIAB Study Group (2002)( 40 ), Substudy 2 | Case–control study | 2226 Cases (T1DM): 610 Controls: 1616 | Austria, Latvia, Lithuania, Luxembourg, UK/Northern Ireland | NA; introduction of cow’s milk before 3 months of age | Population-based register of T1DM, diabetes onset before the age of 15 years | No association between risk of T1DM and introduction of cow’s milk before 3 months |
| Rosenbauer et al. (2008)( 44 ) | Case–control study | 2631 Cases (T1DM): 760 Controls: 1871 | Germany | NA; current level of cow’s milk consumption Cases: <5 years of age (mean 3 years) Controls: <6 years of age (mean 3·3 years) | Population-based register of newly diagnosed T1DM, under 5 years of age | Current cow’s milk consumption is associated with lower risk of T1DM; no cow’s milk v. <200 ml/d: OR=0·65 (95 % CI 0·49, 0·88), no cow’s milk v. ≥200 ml/d: OR=0·60 (95 % CI 0·46, 0·79) |
| Sadauskaite-Kuehne et al. (2004)( 39 ) | Case–control study | Overall n: NR Cases (T1DM): 803 Controls: NR | Sweden and Lithuania | NA; introduction of cow’s milk at or after 7 months | Diagnosis of T1DM at a hospital between 5 and 9 years | Introduction of cow’s milk at or after 7 months is protective of T1DM, OR=0·62 (95 % CI 0·39, 0·99) |
| Savilahti and Saarinen (2009)( 37 ) | Nested case–control study | 6209 Cases (T1DM): 45 Controls: 6164 | Finland | NA; first introduction of cow’s milk in the first 12 months of age | Children with T1DM at mean age of 11·5 years reported to national registry | Age of introduction of cow’s milk similar between cases and controls; no diff. in OR for development of T1DM related to introduction of cow’s milk before or after 11 months |
| Sipetic et al. (2005)( 38 ) | Case–control study | 136 Cases (T1DM): 68 Controls (siblings): 68 | Serbia | NA; age at introduction of cow’s milk | Diagnosis of T1DM according to WHO at a hospital at 16 years of age or younger | Introduction of cow’s milk at younger than 5 months v. later than 5 months: no relation after adjustment for other relevant factors |
| Thorsdottir et al. (2000)( 41 ) | Case–control study | 220 Cases: (T1DM): 55 Controls: 165 | Iceland | NA; age at introduction of cow’s milk (between 1 and 6 months) | Children with T1DM with average age of 12·5 years | No association between age of introduction of cow’s milk and development of T1DM later in life |
| Verge et al. (1994)( 43 ) | Case–control study | 475 Cases (T1DM): 217 Controls: 258 | Australia | NA; age at introduction of cow’s milk (<7 months, 7–12 months, >12 months) | Population-based incidence register of T1DM, diabetes onset before age of 15 years | No association between T1DM and age at introduction of cow’s milk |
| Asthma | ||||||
| Van Asperen et al. (1984)( 49 ) | Prospective cohort study | 79¶ Cow’s milk before 4 months: 51 No cow‘s milk before 4 months: 28 | Australia | Comparison between cow’s milk consumption before 4 months and no cow’s milk | Wheeze (any history of wheezing, doctor-diagnosed); rhinitis (for at least 4 weeks, doctor-diagnosed) | Wheeze: Cow’s milk: 16/22 (31·3 %) No cow’s milk: 6/22 (21·4 %) (P=NS) Rhinitis: Cow’s milk: 27/44 (52·9 %) No cow’s milk: 17/44 (60·7 %) (P=NS) |
| Wijga et al. (2003)( 47 ) | Prospective cohort study | 2978 Consumption frequency: daily (6–7 d/week), regularly (1–5 d/week), rarely (less than once per week); n=NR | Netherlands | NA; cow’s milk consumption at 2 years of age; asthma diagnosis at 3 years of age | Asthma (‘ever asthma’: doctor’s diagnosis of asthma; ‘recent asthma’: doctor’s diagnosis plus asthma symptoms or use of asthma medication in the last 12 months) | Full-cream milk: Daily v. rare consumption associated with ever asthma: adj. OR=0·54 (95 % CI 0·34, 0·88) and recent asthma: adj. OR=0·53 (95 % CI 0·30, 0·92) Semi-skimmed milk: No sign. associations between consumption frequency and asthma |
| Growth | ||||||
| Daly et al. (1996)( 26 ) | RCT | 100 IG (cow’s milk): 50 CG (Fe-supplemented follow-on formula): 50 | UK | 12 months (from 6 to 18 months of age) | Growth | No sign. diff. in Z-scores for weight-for-age, height-for-age, weight-for-height |
| Wiley (2010)( 46 ) | Retrospective cohort study | 1493 Quartiles of milk intake; n=NR | USA | NA; children aged 2–4 years | BMI percentiles | Diff. in BMI percentiles across milk quartiles: higher BMI in Q4 v. Q1, Q2, Q3 (β adj. for energy=−6·3, −11·8, −6·7; P<0·05) |
| Development | ||||||
| Williams et al. (1999)( 27 ) | RCT | 100 IG (cow’s milk): 50 CG (Fe-supplemented follow-on formula): 50 | UK | 12 months (from 6 to 18 months of age) | Psychomotor development (Griffiths scale) | Griffiths general quotient scores declined in both groups, but no sign. diff. between groups |
| Atopic dermatitis (eczema) | ||||||
| Roduit et al. (2012)( 50 ) | Prospective cohort study | 724** Cow’s milk between 3 and 12 months: 247 No cow’s milk within 12 months: 477 | Austria, France, Finland, Germany, Switzerland | Comparison between cow’s milk consumption before 12 months and no cow’s milk | Atopic dermatitis with onset after the first year | Lower risk for atopic dermatitis with onset after the first year when cow’s milk introduced within the first year of life: adj. OR=0·52 (95 % CI 0·30, 0·92) |
| Van Asperen et al. (1984)( 49 ) | Prospective cohort study | 79¶ Cow’s milk before 4 months: 51 No cow‘s milk before 4 months: 28 | Australia | Comparison between cow’s milk consumption before 4 months and no cow’s milk | Atopic dermatitis (doctor-diagnosed) | Atopic dermatitis: Cow’s milk: 22/38 (43·1 %) No cow’s milk: 16/38 (57·1 %) (P=NS) |
| Zutavern et al. (2004)( 45 ) | Prospective cohort study | 620†† Cow’s milk before 6 months: 407 Cow’s milk after 6 months: 213 | UK | Comparison between cow’s milk consumption before and after 6 months of age (age of infants 1 year) | Eczema (doctor-diagnosed), atopy (skin-prick test), wheezing defined at 5 to 5·5 years of age | Higher risk for eczema when cow’s milk introduced after 6 months, adj. OR=1·7 (95 % CI 1·1, 2·5); prevalence of eczema 32·2 % v. 41·2 % when cow’s milk introduced before v. after 6 months (P=0·032); no diff. in other outcomes (pre-school wheezing, transient wheezing, atopy) |
| Gastrointestinal blood loss | ||||||
| Fomon et al. (1981)( 30 ) | nRCT | 41‡ IG (cow’s milk): 21 CG (follow-on formula): 20 | USA | 2·8 months (from 3·7 to 6·5 months of age) | Infants with guaiac-positive stools;Total number of guaiac-positive stools | At 4·7 months: proportion of infants with guaiac-positive stools 35 % in IG v. 0 % in CG (P=0·01) After 4·7 months: no stat. sign. diff. At 4·7 months: total number of guaiac-positive stools 12·5 % in IG v. 0 % in CG (P<0·003) After 4·7 months: no stat. sign. diff. |
| Thomas et al. (1986)( 36 ) | Prospective cohort study | 820 E1 (cow’s milk): 146 E2 (breast-feeding): 354 E3 (formula): 320 | USA | 6 months (from 6 to 12 months of age) | Intestinal bleeding: FH positivity, tetramethylbenzidine-Hematest reactions, orthotolidine-Hematest method | No stat. sign. diff. in FH positivity rates between groups: E1: 2·9 %, E2: 2·1 %, E3: 1·9 % (P=NS) No stat. sign. diff. in tetramethylbenzidine-Hematest reactions between groups: E1: 2·7 %, E2: 3·5 %, E3: 5·2 % (P=NS) Slightly increased incidence of orthotolidine-Hematest reactions for E1 v. E2+E3 (combined) (P<0·05): E1: 9·6 %, E2: 4·1 %, E3: 0·1 % |
| Tunnessen and Oski (1987)( 29 ) | nRCT | 192 IG (cow’s milk): 71 CG (Fe-supplemented follow-on formula): 121 | USA | 6 months (from 6 to 12 months of age) | Total number of guaiac-positive stools | No stat. sign. diff. between study groups |
| Woodruff et al. (1972)( 48 ) | nRCT | 38 IG (cow’s milk): 13 CG (formula): 25 | USA | 10 months (from 2 to 12 months of age) | Proportion of infants with at least 1 guaiac-positive stool in 3 months (2 stools per month tested for guaiac determination, rated positive when at least 2 or more were reported positive) | 3 months: IG 11/12 (91·7 %), CG 11/25 (44 %) 6 months: IG 9/13 (69·2 %), CG 13/25 (52 %) 9 months: IG 10/12 (83·3 %), CG 16/24 (66·7 %) 12 months: IG 7/11 (63·6 %), CG 12/22 (54·5 %) No stat. sign. diff. at any time point |
| Exudative protein loss | ||||||
| Thomas et al. (1986)( 36 ) | Prospective cohort study | 820 E1 (cow’s milk): 146 E2 (breast-feeding): 354 E3 (formula): 320 | USA | 6 months (from 6 to 12 months of age) | Exudative protein loss (FA1AT concentration) | Small diff. in FA1AT levels (P<0·0001): E2>E3>E1 |
IDA, Fe-deficiency anaemia; T1DM, type 1 diabetes mellitus; RCT, randomized controlled trial; nRCT, non-randomized controlled trial; CG, control group; E, exposure group; IG, intervention group; NR, not reported; NA, not applicable; SF, serum ferritin; EP, erythrocyte porphyrin; MCV, mean corpuscular volume; TfR, serum transferrin receptors; cu μ, cubic micron calculated according to Wintrobe; FH, faecal Hb; FA1AT, faecal α1-antitrypsin; stat., statistically; sign., significant; diff., difference; Q, quartile; adj., adjusted.
*
Cow’s milk consumption is always whole cow’s milk unless otherwise stated.
†
Children in both groups also received breast milk during the first 2 months of life.
‡
We report only data on boys, because girls received either pasteurized cow’s milk or extensively heat-treated cow’s milk, but no infant formula.
§
We report only data on white infants.
||
Blood samples were only available for ninety-seven children.
¶
The original cohort included ninety-two children.
**
In total, 1041 children were included in the study, but the analyses were restricted only to children having no atopic dermatitis in the first year (n 724).
††
The original cohort included 642 children.