Kramer MS, Kakuma R. The optimal duration of exclusive breastfeeding: a systematic review. Adv Exp Med Biol. 2004;554:63-77. Review. PMID: 15384567

To review available evidence related to lactation and infant feeding recommendations related to lactation

• controlled clinical trials and observational studies
• published in all languages
• examined whether or not exclusive breastfeeding (EBF) until 6 months of age has an impact on growth, development, morbidity, and survival of healthy, term infants and their motohers
• studies of low-birth weight (<2500 g) provided that the infant was born at term (> 37 weeks)
• internal comparison group that was one group of infants who received EBF for > 3 but < 6 months and mixed breastfeeding (MBF) until 6 months of age or later (i.e. infants were introduced to liquid or solid foods between 3 and 6 months of age), and another group of subjects whoe were breastfed exclusively for > 6 months.

• studies based on external comparison with reference data
• studies comparing EBF and MBF from birth
• studies that investigated the effects of age at introduction of nonhuman milk liquid or solid foods, but did not ensure EBF > 3 months prior to their introduction

Identification of studies:

Two independent literature searches were conducted (staff at WHO's Department of Nutrition for Health and Development and one by the authors)

WHO search (August 22, 2000)

• MEDLINE ( 1966-August, 2000)
• Pre-MEDLINE (Index Medicus previous to 1966)
• CINAHL (1982 toJune, 2000)
• HealthSTAR ( 1975-August 2000)
• EBM Reviews-Best Evidence (1991 to July/August, 2000)
• Cochrane Database of Systematic Reviews (Issue 2, 2000)
• CAB Abstracts (1973 to July 2000)
• EMBASE-Psychology (1987 to 3rd Quarter, 2000)
• Econlit (1969 to August, 2000)
• Index Medicus for the WHO Eastern Mediterranean (IMEMR)
• African Index Medicus (AIM)
• Lilacs

• MeSH terms: "breast feeding", and otherwise the free language terms "breastfeeding", " breast feeding", or breast-feeding combined with "exclusive" or "exclusively"

Author search (August 12, 2000)

• MEDLINE (1966 to week 3, September, 2000)
• CINAHL (1982 to April 2000)
• HealthSTAR (1975 to August, 2000)
• BIOSIS (1989 to 2000)
• CAB Abstracts (1973 to June 2000)
• Cochrane Database of Systematic Reviews (Issue 3, 2000)
• Cochrane Controlled Trials Register (Issue 3, 2000)
• EMBASE-Medicine (1980 to present)

• MeSH terms: "breast feeding", "infant", and "growth"

Data abstraction: stratified by study design (controlled trials vs observational studies) and provenance (developing vs. developed country)

Assessment of study quality:

• Cochrane criteria for assessing the adequacy of randomization and concealment of controlled clinical trials
• the 5-point Jadad scale was used to examine the quality of randomized controlled trials
• Observational studies (cohort, case-control, and cross-sectional) were assessed for: control fro confounding, losses to follow-up, and assessment of the outcome
• Quality assessements of eligible studies carried out independently by 2 reviewers; disagreement solved by consensus

Design : systematic review

Statistical Analysis :

• conducted using Review Manager 4.2 software for preparing Cochrane review
• effect measures reported as the fixed-effect weighted mean difference (WMD) and its 95% confidence interval (CI)
• for continuous outcomes, a positive WMD denotes a more favorable value in the EBF group
• all dichotomous outcomes are formulated as adverse: an RR < 1 denotes that the EBF group had a lower risk of the outcome than the MBF group

Dependent Variables

• weight and length gain
• weight-for-age and length-for-age z-scores
• head circumference
• iron status
• gastrointestinal and respiratory infectious morbidity
• atopic eczema
• asthma
• neuromotor development
• duration of lactational amenorrhea
• maternal postpartum weight loss

Independent Variables

• exclusive breastfeeding (EBF): breastfeeding only
• mixed breastfeeding (MBF): receive complementary foods in addition to breast milk (juices, formula, other milks, other liquids, solid foods)

Number of studies identified: N=2,668

• WHO search: N=1,035 after removing duplicates
• Author search: N=1,845, of which 1,633 were different from those identified in WHO search

Number of unique citations: N=38 comprising 19 separate studies

Location: Canada and Switzerland

Key Findings

• Data from 2 trials in a developing country (Honduras) found prolonged breastfeeding to be associated with more rapid maternal postpartum weight loss.

Other Findings

• Controlled clinical trials and cohort observational studies from either developing or developed countries, suggest that infants who continue to be breastfed exclusively for 6 months show deficits in weight or length gain compared with infants who receive complementary feeding in addition to breasfeeding after 3 or 4 months. However, data are insufficient due to low sample sizes to rule out a modest increase in risk of undernutrition with exclusive breastfeeding for 6 months.
• Data are conflicting with respect to iron status but suggest that in developing countries, where iron stores of newborn infants may be suboptimal, exclusive breastfeeding without iron supplementation through 6 months may compromies heatologic status.
• One large randomized trial in a developing country (Belarus), infants who continue to breasfeed for 6 months or more appear to have a significantly reduced risk of one or more episodes of gastrointestinal tract infection.
• No significant reduction in risk of atopic eczema, asthama, or other atopic outcomes were demonestrated in studies from Finalnd, Australia, and Belarus.
• Data from 2 Honduran trials suggest that exclusive breastfeeding through 6 mnonths of age is associated with delayed resumption of menses.

No objective evidence of a "weanling's dilemma' was found. Large randomized trials are recommended in both developed and developing countries to ensure that exclusive breastfeeding for 6 months does not increase the risk of undernutrition (growth faltering), to confirm the health benefits reported thus far, and to investigate other potential effects on health and development, especially over the long-term.