Note: for non-commercial purposes only

Transcription

1 Note: for non-commercial purposes only Prolonged, exclusive breastfeeding & adiposity, stature & blood pressure: Promotion of Breastfeeding Intervention Trial (PROBIT III) Richard M Martin, Rita Patel, Michael Kramer, Lauren Guthrie, Konstantin Vilchuck, Natalia Boghdanovich, Natalia Sergeichick, Irina Mitroshenka, Matthew W Gillman, George Davey Smith, Emily Oken University of

2 Potential child health benefits of breastfeeding Increased stature Protection against : Obesity CVD risk factors blood pressure, insulin resistance, hyperlipidaemia Problems with the evidence base Based on observational studies Residual confounding Selection bias Publication bias University 2 of

3 Mean difference in BMI: BF v formula fed (36 studies) M artin et al (70) F al l et al (64) Rich-Edwards et al (59) W adsworth et al (53) M artin et al (52) Ravell i et al (50) P arsons et al (33) P oulton and W illiam s (26) B ynner (26) Leeson et al (24) Victora et al (18) T en Towns (15) G illm an et al (12) B ergm ann et al (11) Sung et al (11) T oschke et al (6-14) M affei s et al (10) Li ese et al (10) F rye and Heinri ch (10) M ichaelsen (10) Li et al (8) F om on et al (8) Rona at al (8) M artin et al (8) Langnase et al (6) W hincup et al (6) O 'Call aghan et al (5) S cagli oni et al (5) von K ri es et al (6) G rum mer-s trawn, M ei (4) Hediger et al (4) Armstrong & Reil ly (3) Butte et al (2) Baranowski et al (2) de Bruin et al (2) A gostoni et al (1) Com bi ned Fixed-effect: (95% CI -0.06, -0.03) Mean difference in BMI (kg/m²) Breast feeding better Breast feeding worse Owen et al, AJCN, 2005;82: University 3 of

4 Mean difference in BMI: effect of adjustment for important confounders 0.05 Mean difference in BMI (kg/m²) Adjustments in 11 studies Age Age, maternal smoking Age, maternal BMI Age, social class Age, social class, maternal smoking and BMI Owen et al, AJCN, 2005;82: University of

5 Mean difference in BMI: effect of adjustment for important confounders 0.05 Mean difference in BMI (kg/m²) Adjustments in 11 studies Age Age, maternal smoking Age, maternal BMI Age, social class Age, social class, maternal smoking and BMI Owen et al, AJCN, 2005;82: University of

6 Mean difference in BMI: effect of adjustment for important confounders Mean difference in BMI (kg/m²) Adjustments in 11 studies Age Age, maternal smoking Age, maternal BMI Owen et al, AJCN, 2005;82: Age, social class Age, social class, maternal smoking and BMI University of

7 Mean difference in BMI: effect of breast feeding duration (6 studies) 0.2 Mean difference in BMI (kg/m²) P=0.99 P=0.001 After adjustment Before adjustment -0.6 <5 months 5-8 months >8 months Owen et al, AJCN, 2005;82: University 7 of

8 Mean difference in BMI: effect of breast feeding duration (6 studies) 0.2 Mean difference in BMI (kg/m²) Adjusted for social class, parental BMI, maternal smoking <5 months 5-8 months >8 months P=0.99 P=0.001 After adjustment Before adjustment Owen et al, AJCN, 2005;82: University 8 of

9 Solution: RCT with analysis by intention to treat Best way to minimize multiple biases Randomization to breast vs artificial feeding is not feasible / ethical The solution is a RCT of an intervention to promote BF exclusivity & duration Overlap of BF behaviors requires very large sample size University 9 of

10 PROBIT PROmotion of Breastfeeding Intervention Trial Follow-up of A Cluster-Randomized Trial in the Republic of Belarus University 10 of

11 Trial design RCT to promote breastfeeding exclusivity & duration, based on WHO/UNICEF BFHI Stratified, cluster randomization of 31 maternity hospitals & one affiliated polyclinic per hospital In , 17,046 healthy BF newborns >37 wks & >2500g enrolled during postpartum stay University 11 of

12 Baseline Comparison Maternal Age & Education (%) University 12 of

13 Baseline Comparison No. of siblings, prev BF, CS, smoking, atopic FH (%) 0 other child 1 other child >=2 other children Previous BF >=3 mo Cesarean delivery Maternal smoking Atopic family history Control Experimental University 13 of

14 Degree of Breastfeeding (%) Predominant at 3 mo Predominant at 6 mo Exclusive at 3 mo Exclusive at 6 mo Control Experimental University 14 of

15 Long-term follow-up of PROBIT Created two randomized cohorts differing substantially in exclusivity / duration of BF Analysis by intention to treat enables strong causal inferences with respect to BF effects on long-term outcomes Intervention had significant benefits on: GI infection in infancy (PROBIT I) Atopic eczema in infancy (PROBIT I) IQ at 6.5 years (PROBIT II) University 15 of

16 PROBIT III Follow-up at 11.5 yrs between Jan 2008 to June 2010 Anthropometry CVD risk factors (BP; glucose; insulin; adiponectin; apo A1; apo B; IGF-I) > 13,500 children have been seen (80%) 11,674 (68%) have data entered to date Interim results are presented today, as still over 2000 records to enter University 16 of

17 Comparison By Follow-Up: Probit III Maternal Age & Education (%) <20 yr yr >=35 yr Incomplete secondary Complete secondary Partial university Complete university Followed Up Not Followed Up University 17 of

18 Comparison By Follow-Up : Probit III Older Sibs, Maternal Smoking, & Gender (%) 0 older sibs 1 older sib >=2 older sibs Maternal smoking Male gender Followed Up Not Followed Up University 18 of

19 Interim conclusions prolonged/exclusive BF at 11.5 yrs: Stature: Small positive ass n with height (leg-length) Adiposity: No important reduction in adiposity Blood pressure: No important reduction in BP In this interim analysis, the 95%CIs indicate that small beneficial or adverse effects cannot be ruled out These results are not due to selection bias or confounding, unlike observational studies Breastfeeding improves IQ and protects against GI infections and atopic eczema in infancy University 19 of

20 Спасибо Funded by EU FP6 (EARNEST), NIH (USA) & CIHR University of