Context Current evidence that breastfeeding is beneficial for infant and child
health is based exclusively on observational studies. Potential sources of
bias in such studies have led to doubts about the magnitude of these health
benefits in industrialized countries.
Objective To assess the effects of breastfeeding promotion on breastfeeding duration
and exclusivity and gastrointestinal and respiratory infection and atopic
eczema among infants.
Design The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized
trial conducted June 1996–December 1997 with a 1-year follow-up.
Setting Thirty-one maternity hospitals and polyclinics in the Republic of Belarus.
Participants A total of 17 046 mother-infant pairs consisting of full-term singleton
infants weighing at least 2500 g and their healthy mothers who intended to
breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up.
Interventions Sites were randomly assigned to receive an experimental intervention
(n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health
Organization and United Nations Children's Fund, which emphasizes health care
worker assistance with initiating and maintaining breastfeeding and lactation
and postnatal breastfeeding support, or a control intervention (n = 15) of
continuing usual infant feeding practices and policies.
Main Outcome Measures Duration of any breastfeeding, prevalence of predominant and exclusive
breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes
of gastrointestinal tract infection, 2 or more episodes of respiratory tract
infection, and atopic eczema during the first 12 months of life, compared
between the intervention and control groups.
Results Infants from the intervention sites were significantly more likely than
control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%;
adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69),
were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P = .01), and had a significant reduction in the risk of 1 or more
gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI,
0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI,
0.31-0.95), but no significant reduction in respiratory tract infection (intervention
group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28).
Conclusions Our experimental intervention increased the duration and degree (exclusivity)
of breastfeeding and decreased the risk of gastrointestinal tract infection
and atopic eczema in the first year of life. These results provide a solid
scientific underpinning for future interventions to promote breastfeeding.
Breastfeeding has been widely reported to reduce the risk of infection1-11
and atopic disease1,12-15
in the recipient infant and child. The effect of breastfeeding in protecting
against infection is more striking, and thus easier to demonstrate, in settings
where poverty, malnutrition, and poor hygiene are prevalent.2-5
All of the scientific evidence regarding breastfeeding and morbidity in healthy,
full-term infants is based on observational studies, because it is neither
feasible nor ethical to randomly assign such infants to be breastfed vs formula-fed.
Such studies are plagued by numerous sources of bias related to measurement,
selection, confounding, and reverse causality.16-18
These potential biases have created doubt about the magnitude, and even the
existence, of a protective effect of breastfeeding against infection in developed
country settings.18
A rigorous and feasible research strategy to overcome these biases would
be to assess whether infants who are randomly allocated to a breastfeeding
promotion intervention experience a reduced risk of infection. The mother's
decision to initiate breastfeeding is usually made prenatally or even before
becoming pregnant and prenatal interventions are often logistically difficult
and expensive.19 Therefore, it may be preferable
to focus on improving duration and exclusivity among women who have decided
to initiate breastfeeding. The World Health Organization (WHO) and United
Nations Children's Fund (UNICEF) have combined 10 such interventions ("steps")
in developing the Baby-Friendly Hospital Initiative (BFHI, available at http://www.unicef.org/programme/nutrition/infantfe/tensteps.htm).20 Based on systematic reviews of controlled clinical
trials available in the Cochrane Database of Systematic Reviews,21-24
evidence suggests that duration and exclusivity of breastfeeding are increased
by help with positioning and other aspects of breastfeeding technique (step
5), demand feeding (step 8), and postnatal support (step 10).
The Promotion of Breastfeeding Intervention Trial (PROBIT) builds on
the scientific evidence concerning components of the BFHI. Not only is PROBIT
the first randomized trial of the BFHI as a whole, but the large number of
infants and mothers studied provides an opportunity to assess the direct relationship
between a breastfeeding promotion intervention and infant health and the experimental
link between infant feeding and infant morbidity in healthy mothers and their
infants.
This study was a multicenter randomized controlled trial using cluster
randomization. Maternal hospitals and their corresponding polyclinics, the
"clusters" randomized in our study, were originally paired according to geographic
region within Belarus (Minsk city, Minsk region, Brest, Mogilev, Gomel, Vitebsk,
and Grodno), urban vs rural status, number of deliveries per year (±500
if <2500, or ≥2500), and breastfeeding initiation rates at hospital
discharge (±5%). Most of the maternity hospitals located in large cities
(Minsk, Vitebsk, Brest, and Mogilev) are affiliated with several polyclinics.
To maximize efficiency, enrollment of mothers was limited to those whose
infants were to be followed up at a single selected polyclinic affiliated
with each of these large maternity hospitals. Intervention allocation was
based on a double-randomization procedure. First, a random number table was
used to assign a 2-digit random number to each of the study sites. Within
each pair, the hospital and polyclinic sites corresponding to the higher and
lower numbers were assigned to interventions A and B, respectively. Later,
at a public gathering of the Canadian and Belarussian investigators, a coin
flip determined that B sites would receive the experimental intervention,
and A sites would receive the control intervention.
We chose to carry out this trial in Belarus rather than North America
or Western Europe because maternity hospital practices in Belarus and other
former Soviet republics are similar to those in North America and Western
Europe 20 to 30 years ago and thus provide a greater potential contrast between
intervention and control study sites. However, Belarus resembles Western developed
countries in 1 very important respect: basic health services and sanitary
conditions are very similar. An uncontaminated water supply is ensured and
monitored throughout the republic by public health authorities, and hospital
clinics are abundant and readily accessible, even in rural areas.
Mothers were considered eligible for participation if they expressed
an intention to breastfeed on admission to the postpartum ward, had no illnesses
that would contraindicate breastfeeding or severely compromise its success,
and had given birth to a healthy singleton infant of 37 weeks' or more gestation,
2500 g or more birth weight, and Apgar score 5 or higher at 5 minutes. The
study received approval from the institutional review board of the Montreal
Children's Hospital, and signed consent in Russian was obtained from all participating
mothers.
The experimental intervention was modeled on the BFHI. Because no breastfeeding
support groups existed in Belarus at the time PROBIT was designed, step 10
(postnatal support) of the BFHI was expanded to include the intervention polyclinics.
Participants, usually the chief obstetrician and chief pediatrician, from
each of the intervention maternity hospitals and polyclinics, respectively,
received the 18-hour BFHI lactation management training course, which was
organized by the European Regional Office of the WHO. The course emphasized
methods to maintain lactation, promote exclusive and prolonged breastfeeding,
and resolve common problems.
Full implementation of the experimental intervention required 12 to
16 months to train all midwives, nurses, and physicians providing care to
study mothers and infants during labor, delivery, and the postpartum hospital
stay, and all pediatricians and nurses working at the polyclinics. Monitoring
visits by members of the Canadian and Belarussian Steering prior to and during
recruitment and follow-up at each site ensured that the hospital and polyclinic
procedures and policies were consistent with the BFHI at the intervention
sites, and that the control sites did not institute any changes that would
render their maternity hospitals or polyclinics more baby friendly.
Sociodemographic and clinical information was recorded on an enrollment
form completed during the postpartum stay. In Belarus, infants are seen monthly
for routine well-child visits and whenever they are ill. At 1, 2, 3, 6, 9,
and 12 months, polyclinic pediatricians completed a data form containing detailed
information about infant feeding; measurement of infant weight, length, and
head circumference; the occurrence of symptoms of gastrointestinal or respiratory
tract infection, rash, other illnesses; and hospitalizations since birth or
the most recent clinic visit. In the case of 1 or more missed clinic visits,
data were updated at the next study visit to include all illness occurring
since the previous study visit and the date of weaning, if applicable.
The primary study outcome was the risk of 1 or more episodes of gastrointestinal
tract infection. Secondary outcomes included the risk of 2 or more episodes
of any respiratory tract infection (including upper respiratory tract infection,
otitis media, croup, wheezing, or pneumonia), 2 or more upper respiratory
tract infections; atopic eczema; recurrent (≥2 episodes) wheezing; the
prevalence of any breastfeeding at 3, 6, 9, and 12 months of age; and the
prevalence of exclusive and predominant breastfeeding at 3 and 6 months. Consistent
with WHO definitions,25 infants were considered
as exclusively breastfed for 3 or 6 months if they received no solids, nonbreast
milk, or water or other liquids (other than vitamins or medications) at all
visits up to and including the 3- and 6-month visits, respectively. They were
considered predominantly breastfed at these ages if they received no solids
or nonbreast milk; juices, water, teas, and other liquids were permitted in
this category. The criteria for gastrointestinal and upper respiratory tract
infection were based on the algorithms of Rubin et al,6
modified to ensure a minimum duration of 2 days: at least 2 symptoms among
increased stool frequency, loose stools, vomiting, and temperature greater
than 38.5°C for gastrointestinal tract infection and at least 2 symptoms
among runny nose, cough, fast breathing, and temperature greater than 38.5°C
for upper respiratory tract infection. Rashes were classified as atopic eczema
if they lasted at least 2 weeks or recurred after clearing for at least 1
week, were itchy, and occurred on the face and/or the extensor surfaces of
the arms and/or the extensor surfaces of the legs.
Based on the available evidence concerning the effectiveness of the
individual components of the BFHI, we estimated that the intervention would
reduce breastfeeding discontinuation by 3 months from 50% (reported in a prior
Belarussian Ministry of Health survey) to 35%. Three months of any breastfeeding
was chosen as the primary basis for calculating breastfeeding prevalence based
on the data of Howie et al7; in initially breastfed
infants who were weaned at 13 weeks vs those breastfed to any degree and for
at least 13 weeks, the relative risk of gastrointestinal tract infection (the
primary outcome) associated with early weaning was approximately 2. From our
previous surveillance studies in French day care centers using similar surveillance
techniques and definitions,26 we estimated
that the expected delay in weaning would reduce the risk of 1 or more episodes
of gastrointestinal tract infection from 60% to 54%.
Assuming 500 mothers and infants enrolled at each maternity hospital,
a design using 15 pairs of study sites would provide a power of greater than
80% to detect such a difference at a 2-sided α level of .05, even assuming
a worst-case scenario of high variability between sites and totally ineffective
pairing.27,28 To ensure that 15
hospital pairs would be included in the final study sample, we randomized
17 pairs to provide a margin of security against withdrawals or unforeseen
logistical problems at a few sites. As it turned out, 2 of the maternity hospitals
refused to carry out their allocated intervention following randomization,
and 1 of the polyclinics was discovered to have falsified their outcome data,
leaving 31 sites (16 intervention and 15 control) and 15 intact original pairs
(Figure 1).
Cohort Recruitment, Data Validation, and Follow-Up
Recruitment began in June 1996 and by October 1996 all randomized sites
were recruiting mothers and infants. To ensure an adequate sample size at
each of the study sites, recruitment continued until the end of December 1997.
After eliminating the 749 mother-infant pairs enrolled at the site excluded
because of falsified outcome data, a total of 17 046 mother-infant pairs
were enrolled at the 31 remaining sites, making this, to our knowledge, the
largest randomized trial ever undertaken in the area of human lactation.
Because the observers of the clinical outcomes were the same pediatricians
involved in implementing the experimental or control interventions, they could
not be blinded to the intervention vs control status of the study infants.
One routine audit of data validity was therefore carried out at each study
site. Twenty polyclinic charts were selected at random and the data contained
therein bearing on gastrointestinal tract infections, respiratory tract infections,
and any breastfeeding at 3 months were compared with the data on these outcomes
recorded on the PROBIT polyclinic visit forms. Of the 20 audited polyclinic
charts, maternal interviews were also carried out for 10. The audit compared
the occurrence of 1 or more gastrointestinal tract infections and 2 or more
respiratory tract infections. For breastfeeding at 3 months, agreement was
considered present if the date of weaning in the polyclinic chart or by maternal
interview was within 15 days of the date recorded on the PROBIT polyclinic
visit forms.
Of the 17 046 mother-infant pairs enrolled, only 555 (3.3%) were
lost at some time during their first year, including 297 (3.4%) in the intervention
group and 258 (3.2%) in the control group (Figure 1). However, because information on breastfeeding duration
and illness episodes was updated at each clinic visit, analysis of each outcome
is based on all infants remaining in the study at the time that outcome was
measured, even if they were lost to follow-up before 12 months.
All outcomes were analyzed based on the intention-to-treat principle,
ie, according to randomized allocation to the experimental vs control intervention.
But removal of 2 study sites from 2 different original pairs and data falsification
at a third site undermined our original plan to analyze the trial data using
paired t tests. As recommended by an external monitoring
committee, we based our primary analytic strategy on stratification rather
than pairing, with multivariate modeling of group- and individual-level covariates
to allow statistical inference at the level of individual women and infants.
We used a dichotomous stratification for region, west (Brest and Grodno) vs
east (all others), and urban vs rural location. We compared the intervention
and control groups at baseline using the PROC MIXED procedure in SAS for continuous
variables and PROC FREQ for categorical variables (version 6.12; SAS Institute,
Cary, NC). The primary analysis of study outcomes was implemented using the
GLIMMIX procedure in the same version of SAS, with the cluster as the unit
of analysis and cluster-based indicators for region and urban vs rural status.
To control for individual-level covariates, multivariate models (using GLIMMIX
in SAS) for breastfeeding outcomes contained individual-level terms for birth
weight (2500-2999, 3000-3499, ≥3500 g), maternal age (<20, 20-34, ≥35
years), and history of having breastfed a previous infant for 3 months for
longer (yes vs no). For gastrointestinal and respiratory tract infection,
the individual-level covariates included birth weight and number of other
children living in the household (0, 1, ≥2); maternal smoking during pregnancy
(yes vs no) was also included for respiratory tract infection. Finally, for
analysis of atopic eczema and other rashes, only family atopic history (positive
history of asthma, allergic rhinitis, or atopic eczema in the mother, the
father, or a sibling) was included as an individual-level covariate. Results
of all GLIMMIX models are reported as adjusted odds ratios (ORs) and 95% confidence
intervals (CIs).
As shown in Table 1, the
randomization produced intervention and control sites with similar distributions
of maternal age, maternal education, atopic family history, previous breastfeeding
experience, other children living in the household, smoking during pregnancy,
cesarean delivery, and infant sex distribution. Small differences in several
of these categorical variables are attributable to the cluster-based randomization.
The mean birth weight, gestational age, and 5-minute Apgar scores were virtually
identical in the 2 groups.
Table 2 summarizes the audit
results for any breastfeeding, 1 or more episodes of gastrointestinal tract
infection, and 2 or more episodes of respiratory tract infection. Chance-corrected
agreement was high for all 3 outcomes, as shown by the high levels of κ,
and there was no difference in degree of overreporting or underreporting according
to intervention vs control status.
Table 3 and Figure 2 summarize the results for any breastfeeding. In the control
group, 60% of mothers (range among sites, 46%-78%) were still breastfeeding
to some degree at 3 months, considerably higher than the 50% we had estimated
based on data prior to initiating our trial. Nonetheless, the intervention
group had significantly higher rates of continued breastfeeding at 3 months
(73%; range, 64%-87%) and throughout the first year. Even larger differences
were observed for degree of breastfeeding, although extremely low rates of
exclusive and, at 6 months, predominant breastfeeding in the control group
led to GLIMMIX models that did not adequately converge and hence to unreliable
estimates of the adjusted ORs. Statistical significance for these comparisons
was assessed using unpaired t tests. The proportion
of women exclusively breastfeeding at 3 months was 7-fold higher in the experimental
group (43.3% vs 6.4%; P<.001 by unpaired t test) and more than 12-fold higher at 6 months (7.9%
vs 0.6%; P = .01). Nearly twice as many women in
the intervention group were predominantly breastfeeding at 3 months (51.9
vs 28.3%; adjusted OR, 0.28; 95% CI, 0.16-0.49) and nearly 7 times as many
at 6 months (10.6% vs 1.6%; P = .003).
As shown in Table 4, the
proportion of infants in the control group who experienced 1 or more episodes
of gastrointestinal tract infection in the first year was only 13.2%, far
lower than the 60% we had estimated. Nonetheless, the intervention significantly
reduced this risk by 40%. For the various respiratory tract infection as outcomes
under study, reductions in risk in the intervention group were small and statistically
nonsignificant.
Table 5 summarizes the results
for atopic eczema and other rashes. The occurrence of atopic eczema was reduced
by 46% in the intervention group, with a similar reduction in the risk for
noneczematous rashes. To verify that the reduction in risk of noneczematous
rashes was not merely due to protection against viral exanthems and other
infection-related rashes, we also examined the risk for occurrence of noneczematous,
noninfectious rashes; the risk reduction was of comparable magnitude. Multivariate
models showed a significant association between positive family atopic history
and both noneczematous rash (adjusted OR, 1.50; 95% CI, 1.22-1.85) and noneczematous,
noninfectious rash (adjusted OR, 1.49; 95% CI, 1.20-1.85), suggesting that
some of these rashes may have been atopic despite not meeting our clinical
criteria for atopic eczema.
A total of 49 deaths occurred among study infants during the 12 months
of follow-up, 21 in the intervention group and 28 in the control group, for
a total infant mortality rate of 2.3 vs 3.7 per 1000 live births, and an adjusted
OR of 0.78 (95% CI, 0.52-1.42). Of note was the occurrence of only 1 death
attributed to the sudden infant death syndrome (SIDS) among infants in the
intervention group vs 5 SIDS deaths among infants in the control group (P = .12 by unpaired t test; multivariate
model did not converge).
Our breastfeeding promotion intervention, modeled on the BFHI, succeeded
in increasing the duration and exclusivity of breastfeeding in the first year
of life. These effects occurred against a background of a higher-than-expected
breastfeeding duration in the control group. The latter may well be attributable
to deteriorating economic conditions in the country during the trial and the
higher costs of formula feeding. Even though locally made formula was readily
available, it cost nearly 20% of an average monthly salary by the end of the
study. The higher-than-expected breastfeeding duration in the control group
might also be due to the receding memory and reduced fear of breastfeeding
related to the Chernobyl incident in 1986.
Despite our initial overestimate of the incidence of gastrointestinal
tract infection, the risk of such infection was reduced by 40% in the intervention
group. This represents a clinically substantial reduction in risk of this
important cause of infant morbidity and confirms recent results of a small
randomized trial in Mexico.29 The lower-than-expected
incidence of gastrointestinal tract infection is probably related to the fact
that all of the study infants were breastfed initially and that most, even
in the control group, were breastfed for more than 3 months. The prolonged
(approximately 3 years in most cases) obligatory maternity leave and absence
of day care centers for infants in Belarus probably also played a role. The
low incidence of otitis media and wheezing may have a similar explanation.
We do not believe the low incidence of gastrointestinal tract infection reflects
underreporting because the definition and surveillance methods used were similar
to those we used previously in France,28 where
the incidence was far higher, and because our routine audits confirmed the
figures reported on our data forms.
We observed no significant reduction in risk for the respiratory tract
infectious outcomes under study. This may also be due to the universal breastfeeding
initiation in our study cohort, as well as the high rates of breastfeeding
for 3 months or longer, even in the control group. It also reflects the reduced
protective effect of breastfeeding against respiratory tract infection that
has been noted consistently in previous epidemiologic studies.1,2,7,8
We do not believe that the absence of a protective effect reflects nondifferential
error in measurement of respiratory tract infections because these infections
were significantly associated with maternal cigarette smoking (OR, 1.45; CI,
1.17-1.79) for the risk of 2 or more respiratory tract infections.
The experimental intervention also appears to have been successful in
reducing the risk of atopic eczema in the first year of life. Although we
were surprised that the risk of noneczematous, noninfectious rashes was also
reduced in the intervention group, our results suggest that some of these
rashes may have been true atopic eruptions that were misclassified by our
clinical criteria.
Several limitations of our study should be acknowledged. All of the
infectious outcomes were based on clinical criteria; no culture or serologic
data were collected. Such data would have added substantial costs and logistical
problems to an already large and complex study. Nonetheless, our data audits
indicate extremely close agreement between the data recorded on our study
data forms and those recorded in the polyclinic charts, as well as high concordance
with information obtained from direct maternal interviews. More importantly,
we saw no evidence from these audits that infectious outcomes were underreported
in the experimental group or overreported in the control group. Because we
were unable to audit the data for atopic eczema and other rashes, the apparent
protective effect of the intervention on these outcomes should be interpreted
with caution. Our experimental intervention may have been insufficient to
effect a reduction in respiratory tract infectious outcomes; more prolonged
and exclusive breastfeeding than we were able to achieve might have succeeded
in reducing respiratory tract infection. Our study did not have sufficient
statistical power to detect an effect of the intervention on mortality. Nonetheless,
the observed trend toward a reduced risk of SIDS in the intervention group,
although not statistically significant, is consistent with several previous
epidemiologic studies reporting a protective effect associated with breastfeeding.30
Finally, although basic health services and sanitary conditions are
quite similar to those in North America and Western Europe, 2 aspects of the
Belarussian health care system may limit the generalizability of our findings.
First, the highly centralized Belarussian system undoubtedly helped in implementing
the experimental intervention; the intervention maternity hospitals and polyclinics
made remarkable changes, documented during our monitoring visits, in their
approach to breastfeeding within a very brief prerecruitment period (12-16
months). Second, the prolonged (6-7 days) postpartum stay for routine vaginal
deliveries far exceeds those currently found in the West and may help establish
good breastfeeding practices and instill maternal confidence.
Despite these limitations, we believe that PROBIT provides an essential
scientific underpinning, not only for the BFHI, but for future breastfeeding
promotion interventions in both developed and developing country settings.
Moreover, the creation of 2 large randomized cohorts with substantial differences
in the degree and duration of breastfeeding creates a unique opportunity for
future study of longer-term health outcomes, including growth, asthma and
other atopic diseases, neurocognitive development, and common adult chronic
diseases.
1.Kovar MG, Serdula MG, Marks JS.
et al. Review of the epidemiologic evidence for an association between infant
feeding and infant health.
Pediatrics.1984;74:615-638.Google Scholar 2.Jason JM, Nieburg P, Marks JS. Mortality and infectious disease associated with infant-feeding practices
in developing countries.
Pediatrics.1984;74:702-727.Google Scholar 3.Feachem RG, Koblinsky MA. Interventions for the control of diarrhoeal diseases among young children:
promotion of breast feeding.
Bull World Health Organ.1984;62:271-291.Google Scholar 4.Habicht J-P, DaVanzo J, Butz WP. Does breastfeeding really save lives, or are apparent benefits due
to biases?
Am J Epidemiol.1986;123:279-290.Google Scholar 5.Victora CG, Vaughan JP, Lambardi C.
et al. Evidence for protection by breast-feeding against infant deaths from
infectious diseases in Brazil.
Lancet.1987;2:319-322.Google Scholar 6.Rubin DH, Leventhal JM, Krasilnikoff PA.
et al. Relationship between infant feeding and infectious illness: a prospective
study of infants during the first year of life.
Pediatrics.1990;85:464-471.Google Scholar 7.Howie PW, Forsyth JS, Ogston SA, Clark A, du V Florey C. Protective effect of breast feeding against infection.
BMJ.1990;300:11-16.Google Scholar 8.Cunningham AS, Jelliffe DB, Jelliffe EF. Breast-feeding and health in the 1980's: a global epidemiologic review.
J Pediatr.1991;118:659-666.Google Scholar 9.Beaudry M, Dufour R, Marcoux S. Relation between infant feeding and infections during the first six
months of life.
J Pediatr.1995;126:191-197.Google Scholar 10.Dewey KG, Heinig MJ, Nommsen-Rivers LA. Differences in morbidity between breast-fed and formula-fed infants.
J Pediatr.1995;126:696-702.Google Scholar 11.Raisler J, Alexander C, O'Campo P. Breast-feeding and infant illness: a dose-response relationship?
Am J Public Health.1999;89:25-30.Google Scholar 12.Saarinen UM, Backman A, Kajosaari M, Simes MA. Prolonged breast-feeding as prophylaxis for atopic disease.
Lancet.1979;2:163-166.Google Scholar 13.Hide DW, Guyer BM. Clinical manifestations of allergy related to breast and cows' milk
feeding.
Arch Dis Child.1981;56:172-175.Google Scholar 14.Golding J, Emmett PM, Rogers IS. Eczema, asthma and allergy.
Early Hum Dev.1997;49(suppl):S121-S130.Google Scholar 15.Oddy WH, Holt PG, Sly PD.
et al. Association between breast feeding and asthma in 6 year old children:
findings of a prospective birth cohort study.
BMJ.1999;319:815-819.Google Scholar 16.Hill AB. A Short Textbook of Medical Statistics. London, England: Hodder & Stoughton; 1977:27.
17.Sauls HS. Potential effect of demographic and other variables in studies comparing
morbidity of breast-fed and bottle-fed infants.
Pediatrics.1979;64:523-527.Google Scholar 18.Bauchner H, Leventhal JM, Shapiro ED. Studies of breast-feeding and infections: how good is the evidence?
JAMA.1986;256:887-892.Google Scholar 19.Losch M, Dungy CI, Russell D, Dusdieker LB. Impact of attitudes on maternal decisions regarding infant feeding.
J Pediatr.1995;126:507-514.Google Scholar 20.WHO/UNICEF. Protecting, Promoting and Supporting Breastfeeding:
The Special Role of Maternity Services. Geneva, Switzerland: World Health Organization; 1989.
21.Renfrew MJ, Lang S. Feeding schedules in hospitals for newborn infants [Cochrane Review
on CD-ROM]. Oxford, England: Cochrane Library, Update Software;2000; issue 4.
22.Sikorski J, Renfrew MJ. Support for breastfeeding mothers [Cochrane Review on CD-ROM]. Oxford, England: Cochrane Library, Update Software;2000; issue 4.
23.Renfrew MJ, Lang S. Early vs delayed initiation of breastfeeding [Cochrane Review on CD-ROM]. Oxford, England: Cochrane Library, Update Software;2000; issue 4.
24.Renfrew MJ, Lang S. Interventions for improving breastfeeding technique [Cochrane Review
on CD-ROM]. Oxford, England: Cochrane Library, Update Software;2000; issue 4.
25. Indicators for Assessing Breast-Feeding Practices . Geneva, Switzerland: World Health Organization; 1991. WHO Document
WHO/CDD/SER/91.14.
26.Collet J-P, Burtin P, Kramer MS, Floret D, Bossard N, Ducruet T. Type of day-care setting and risk of recurrent infection.
Pediatrics.1994;94(suppl):997-999.Google Scholar 27.Shipley MJ, Smith PG, Dramaix M. Calculation of power for matched pair studies when randomization is
by group.
Int J Epidemiol.1989;18:457-461.Google Scholar 28.Gail MH, Byar DP, Pechacek TF, Corle DK. Aspects of statistical design for the community intervention trial
for smoking cessation (COMMIT).
Control Clin Trials.1992;13:6-21.Google Scholar 29.Morrow AL, Guerrero ML, Shults J.
et al. Efficacy of home-based peer counselling to promote exclusive breastfeeding:
a randomised controlled trial.
Lancet.1999;353:1226-1231.Google Scholar 30.Ford RPK, Taylor BJ, Mitchell EA.
et al. Breastfeeding and the risk of sudden infant death syndrome.
Int J Epidemiol.1993;22:885-890.Google Scholar