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Benefits of breast-feeding

the preterm infantIPOKRaTES Seminar: Neonatal Neurology

May 30th June 2nd, 2011

Cairo, Egypt

Saroj SaigalMcMaster University, Hamilton, Ontario

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Presentation today: Problems in conducting studies on BF in preterm

Properties of human milk, donor milk, fortified human milkShort-term effects of breast-feeding on infection, growth,

neurodevelopment, bonding

Long-term effects of breast-feeding on cognition, blood pressure,

allergies etc

HIV transmission via BF

Summary and recommendations

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Methodologic issues in conducting

studies on breast-feeding

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Problems in conducting nutritionalstudies in preterm infants

Availability of breast milk inadequate Inability to randomize breast-feeding for

ethical reasonsConfounded by severity of illness

Feeding intolerances and NEC

Proportion of total intake by TPN not reported

No information on post-NICU feeding

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Clinical application

Caution should be used in linking intention to breast-feed with substantial milk consumption with actual

breast-feeding.

Separating the emotional aspects of suckling from the

biochemical and immunologic properties of human milk

(gavage-fed preterm infants may be a good model to

delineate these effects)

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Mothers choice to breast-feedand positive health behaviours

antenatal class attendance smoking behaviour immunization

motivation

advantageous parenting lifestyles

higher maternal education and SES

Two-parent family

Positive home environment

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Properties of human milk and

preterm formula

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Composition of term human milk

(unit /L) Foremilk Hindmilk Drip milk

Energy (kcal)* 629 825 540

Fat (g) * 28.6 47.8 22.0 Protein (g) 13.1 13.1 13.0

Calcium (mg) 272 273 280

Sodium (mEq) 3.3 3.1

Zinc (mg) 2.9 2.8

Valentine, JPGN 1994;18:474; McGuire, Arch Dis Child 03

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Weight gain before and afterhindmilk

Valentine et al, 1996

20 -

15 -

10 -

5 -

0 -

25 30 35 40 45 50 55 60 65

Week 1

Week 2

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Protein content ofterm and preterm human milk

0

0.5

1

1.5

2

2.5

3

3.5

0 1 2 3 4 5 6 7 8 9 10 11 12

Preterm

Full term

Schanler et al 1980

Protein

(g.dl.1

)

Mean SEM

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Protein content of pretermhuman milk ( 0 - 12 wks)

0.5

1

1.5

2

2.5

00 1 2 4 6 8 10 12

Preterm Formula

Human Milk

Schanler et al, 1980

Pro

tein

Conte n

t(g/d

L)

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Sodium content of pretermhuman milk: 0 - 12 wks

0.5 1 2 3 4 6 8 100

0

5

10

15

20

25

12

So

dium

Con

tent

(mEq/L

)


Human Milk

Preterm Formula

Duration of Lactation (weeks)

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Effect of maternal fasting during Ramadan

on composition of BM and IQ of children

qDuring fasting, zn, mg, and potassium decreased

significantly in BM

qAlthough the nutritional status of the mother was

affected, there were no significant effects on the

growth or IQ of the children

Rakicioglu et al, Pediatri Int 2006;48:278-83

Azizi et al, Int J Vitam Nutr Res 2004;74:374-80

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Effect of maternal fasting during Ramadanon composition of BM and IQ of children

(contd)

q Because all the nutrient intakes of the mother

were affected during pregnancy and lactation, it

would be prudent to excuse these women from

fasting during Ramadan, if possible

Rakicioglu et al, Pediatri Int 2006;48:278-83

Azizi et al, Int J Vitam Nutr Res 2004;74:374-80

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Unfortified human milk:nutritional concerns

q Poorer rates of growth / nutritional deficits

q Variations in macronutrient composition of EBM

q Significant declines in protein and sodium conc. with

PNA

q Ca and Ph concentrations below requirements

q Compounded by lack of ad libitum feeding and

frequentfluid restrictions

Growing preemies require fortified human milk


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Nutrient Composition of FortifiedHuman Milk

Nutrient

Per 100 ml

Unfortified Fortified

1:50

Fortified

1:25

SSC 24

Energy (kcal) 70 75 82 80

Protein g 1.3 1.85 2.3 2.4

Calcium mmol 0.5 1.98 3.45 3.1

Phosph mmol 0.4 1.43 2.52 2.3

Vitamin A IU 363 670 983 814

Vitamin D IU - 60 119 158

Sodium mmol 1.0 1.3 1.7 1.8

Potassium mmol 1.4 2.2 3 2.5

Iron mg 0.11 0.29 0.46 0.3

Note: maximum protein intake for infants with normal renal function = 4 g/kg/day

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Donor Human Milk

RCT of donor HM vs Preterm formula

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RCT of donor HM vs Preterm formula

in extremely preterm infants (

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Human donor milk vs formula

for VLBW infants

In preterm infants, meta-analysis of 4 trials showed

infants fed DM were 3x less likely to develop NEC

(RR 0.34, 95% CI 0.12, 0.99), McGuire W, Arch Dis Child 2003; 88:F11-14

In VLBW infants, feeding formula vs donor BM

results in short-term growth, but also risk of

NEC (RR 2.5, 95% CI 1.2, 5.1) meta-analysis of 5trials Quigley MA Cochrane database Rev, 2007

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Short-term effects of

breast-feeding

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Benefits of human milk

Relate to:q Nutritional benefits

q Improvements in host defences

q Digestion with absorption of nutrients

q Gastro-intestinal function

q Neurodevelopment

q Maternal psychological well-being


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Suitability of human milk for prematureinfants: host defense benefits

Human milk immune system- Cellular functions

- SigA, lactoferrin, lysozyme

- Bioactive substances- oligosaccharides, nucleotides

Fecal Flora

Enteromammary pathway

- Skin-to-skin care

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Suitability of human milk for prematureinfants: gastrointestinal function

Trophic factors Gastric emptying better

Gut motility improved

Feeding tolerance better

Bioactive substances

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Effect of dose of mothers own milk oninfection-related events and hospital stay

Human Milk>50 mL/kg/d

Human MilkAnd Formula

PretermFormula

No. of Infants 62 63 42

Human milk intake (ml/kg/d) 96 23 20 15 0

Necrotizing enterocolitis, n (%) 1 (2) * 16 (25) 6 (13)

Late-onset sepsis (LOS), n (%) 19 (31)** 29 (46) 22 (48)

LOS and / or NEC, n (%) 19 (31) 35 (56) 25 (54)

Hospital stay (d) 73 19 *** 87 43 88 47

*P

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Study Relative risk (95% CI)

Gross 1981Lucas 1982

Svenningsen 1982 *

Tyson 1983

* Not estimable

Pooled estimate 0.25 (0.06 to 0.98)

0.001 0.02 1 50 1000

Favours human milk Favours formula

Relative risk of confirmed necrotising enterocolitis with human milk versus

formula. Adapted from McGuire W, Anthony MY. Arch Dis Child 2003;88:11-14

NEC: Human milk vs formula

C i th ith HM d

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Comparison growth with HM andfortified HM in premature infants

Human Fortified HumanMilk Milk

Weight gain (g/kg/d) 13 1 17 2 *

Length increment (cm/wk) 0.8 0.2 1.1 0.2 *

Head circumf (cm/wk) 0.8 0.2 1.0 0.2 *

BUN (mg/dL) 5.0 2.8 9.4 4.5 *

Greer & McCormick, J Pediatr 1988;112:961-9

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Adequacy of fortified human milk

q Fortified human milk provides adequate growth,

nutrient retention and biochemical indices

q Precise quantity of nutrients undetermined

q Protection from infection and NEC

q Adequate volume 180 ml/kg essential

F rtific ti n f hum n milk nd

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Fortification of human milk and

neurodevelopment outcome

Randomized trial of partially supplementedhuman milk and human milk fortification in the

NICU did not demonstrate any differences in

neuro-developmental outcome at 18 months

q However, no adverse effects were noted

Lucas et al, 1996

Nutrient enrichment of MM post discharge:

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Nutrient enrichment of MM post-discharge:Growth at 12 months

Prospective RCT of infants 24-32 wks GA:Unfortified MM, n = 102, fortified MM, n = 105, formula, n = 113 for 4

months.

Fortification did not affect duration of BF

Growth with fortification was improved in females during intervention

period only, but not at 12 mths

Formula fed infants achieved better WT and L catch-up

A lower dose of fortification than recommended was used in this study

Zachariassen et al, Pediatrics 2011;127:e995-1003

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Fortification guidelines in NICU

Add fortifiers only when the infant is nearly fully

fed orally:

1 package of human milk fortifier to 25 ml EBM =

84k cal / 100ml, and provides calories, vitamins,

minerals and extra protein requirements

Fortification of Human Milk:

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F f f um MPost-discharge

q Only 1 small RCT of fortified HM (39 infants) found improved growth

rates but no effect on neurodevelopmental outcomes at 18 mths CA

qSince fortifying BM for infants fed directly from the breast is

logistically difficult, fortifiers are offered only to infants with poor

weight gain

qFurther trials are warranted

McCormick FM, Cochrane Database Syst Rev. 2010

Fortification guidelines:

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f gPost-discharge

q Powdered formula 1 g = 5 K Cal

q Addition of powdered formula to every 50 ml EBM:

tsp = 22 K cal/ oz

tsp = 24 K cal/ oz

tsp = 26 K cal/ oz1 tsp = 28 K cal/ oz

q Aim for total fluid intake of 150 ml/ kg with fortified EBM,

8 - 10 feeds */ d (6-8 BF, 2 bottles of fortified EBM)

* Frequent feeding will stimulate milk production

Supplementation of Vitamin D and Iron

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ppPost discharge

qIron is essential for premature infants, particularly if

breast fed. Requirements total up to 15 mg / day

- < 1000g BW: 3-4 mg/ kg

- > 1000g BW: 2-3 mg/ kg

q Vitamin D, aim for 400 IU of Vitamin d/ daily; infants

with darker complexion require 800 IU/ d

(feeds usually provide 40 IU / 100 ml)

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Long-term effects of

breast-feeding

Beneficial effects of breast milk:

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Term Infants

Improved cognitive scores (PPVT-R 3.6 points )

Oddy 03

Improved maternal/child behavioural ratings (not evidentin randomized trial) Kramer 08

Decreased rates of GI infection Kramer 01

No protective effect on asthma and allergies Sears 02, Kramer 01

BP, type 2 diabetes and cholesterol levels Owen 08, Stuebe 05

Risk of overweight at adolescence Gillman 01

Kramer, Pediatrics 2008, BMJ 2007

Breast feeding and brain function

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Breast-feeding and brain functionBF appears to have a broad range of enhanced brain functions:

q rapid maturation of visual function/acuity

q acquired motor skills at an earlier age

q fewer emotional or behavioural problems

q fewer minor neurological problems

qscores on Bayley Scales of Infant Development

Breast milk feeding of ELBW in NICU:

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Breast milk feeding of ELBW in NICU

Outcomes at 18 and 30 months(NICHD)

At 18 and 30 months, ingestion of fortified BMwas associated with:

q higher Bayley MDI scores that persisted

q higher scores for emotional regulation

q fewer rehospitalizations post-discharge

q no differences in growth or CP

Vohr et al Pediatrics 2006;118:e115 23; 2007;120:e953 959

Beneficial effect of BM in the NICU persisted between

18 mths and 30 mths CA

Association of breast milk feeding

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Association of breast milk feeding

of ELBW at 30 months(NICHD)

For every 10ml/kg / day increase in BM

qMDI increased by 0.59 points

q PDI increased by 0.56 points

q BRS percentile score by 0.99 pointsq Sepsis rate by 5%

q Risk of rehospitalization by 5%Maximum benefit 0-2 yearsVohr et al, Pediatrics 2007;120:e953-59;

Weighted Mean Difference in Cognitive

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Developmental Score between Breast-fedand Formula-fed by

Duration of Breast-feeding

Mean Difference

Duration (breast-fed - forumula-fed) 95% CI

4 - 7 wk - 0.02 - 0.71, 0.67

8 - 11 wk 1.68 1.12, 2.25

12 - 19 wk 2.15 1.41, 2.88

20 - 27 wk 2.78 1.94, 3.61

28 wk 2.91 1.73, 4.09Anderson et al, 1999

Adj t d d t i WISC IQ t

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Adjusted advantage in WISC IQ at

age 8 years for breast-fed infants

Advantage p

Verbal Scale + 7.7< .001Performance Scale + 7.9< .0001

Overall IQ + 7.6< .0001

(RCT donor milk or formula supplementation to BF infant)

Lucas et al, 1992

Co-variables of breast milk feeding

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f f g

and IQ at age 8 yrs

Significant multiple factors affecting IQ:

p

Received breast milk + 8.3 IQ < .0001

Social class - 3.5 / class .0004

Mothers education + 2.0 /group .01

Female gender + 4.2 .01

Mechanical ventilation - 2.6 / week .02

Lucas, Lancet 1992

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How good is the evidence linking

breast-feeding and intelligence?

B t f di d d lt i t lli

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Breast-feeding and adult intelligence

Contrary to the studies by Lucas et al, the

mechanisms that link type of infant feeding with

later intelligence may have more to do

with the childs social environment than

with the nutritional quality of human milk (UK

Study)

Gale et al, Lancet 1996;347:1072-5

Systematic review of

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y

breast-feeding studies

q Of 40 publications 1929-01, 27 (68%) concluded

breast-feeding promotes intelligence

q Evidence from 2 best higher quality studies is

less persuasive

q Conflicting evidence regarding breast-feeding

and intelligence

Jain et al, 2002

Breast-feeding and cognitive

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development: Summary ofmeta-analysis

Age: benefit seen at 6 - 23 mths and differences stable ovesuccessive ages

BW: LBW showed larger differences (OR 5.18; CI 3.5, 6.7)

than NBW (OR 2.66; CI 2.1, 3.1)

Dose effect: Cognitive benefit increased with duration of BF

Anderson J et al, 1999

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Other Outcomes

Longer term health benefits due to

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breast-feeding

Protective effect against:

Obesity Owen GG 05Hyperlipidemia Owen CG 06

Hypertension Martin RM 05

Insulin resistance and Type 2 diabetes Gdalevich M01

Atopic disease Gdalevich M 01

Cognitive ability Anderson J 99

Breast milk and later blood pressure

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Breast milk and later blood pressure

Evidence from 2 randomized trials 216 of 926

(23%), children 13-16 yrs:

Lower mean and diastolic BP in infants fed BM

+ DBM vs Term or Preterm formula

(mean 81.9 vs 86.1, 95% CI -6.6 - 1.6, p< .0001)

Supports long-term beneficial effects of BM

(caution: ascertainment bias, despite no

difference in those not followed)

Si h l C l L 2001

Implications of decreased

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Implications of decreased

blood pressure

3mmHg in diastolic has substantial publichealth implications

2mmHg reduces hypertension by 17%, risk ofcoronary heart disease by 6%, and stroke and

ischaemic attacks by 15%

Singhal, Cole, Lucas, 2001

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HIV and Breast-feeding

HIV and breast-feeding in developed

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HIV and breast feeding in developed

countries

Because of 15% risk of HIV infection, HIV infectedmothers universally do not BF their infants.

Risk of infection is particularly greater in the cell-

rich colostrum of BM

Shearer, Pediatrics 2008;121:1046-7

Breast-feeding and transmission of

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HIV-1 randomized trial in Kenya

N = 212 breast fed and 213 formula fed

q Cumulative probability of HIV transmission to

infant was 36.7% in BF and 20.5% in FFq The rate of HIV-1-free survival at age 2 yrs was

58% in BF vs 70.0% in FF (P = .02)

q Use of breast milk substitutes should be

considered

Nduati et al, JAMA 2000;283:1167-74

Breast-feeding and HIV+ve mother:

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Debate

Dilemma highlighted in poor countries

qAvoidance of BF recommended, if affordable

qOtherwise exclusive BF is recommended during

the first 4-6 months of life

qAntiretroviral therapy for the mother and / or

infant extended for 6 months offers a reduction in

transmission of 50% while maintaining BF

Coutsoudis, Early Human dev 2005;81:87-93

Shearer, Pediatrics 2008;121:1046-7

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Breast-feeding:

Conclusions

Conclusions

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q Small, but statistically significant advantages for breast-fed

children from 2 to 5 years

q Advantages more consistent for cognitive skills

q Consistent dose response shown

q Covariables such as maternal education and birth orderadvantage needs to be considered

q Although effect size is small, BF offers the potential for

enhancing the childs development at no risk and little cost.

Conclusions contd

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Overall, despite methodologic problems, the

advantages of breast-feeding premature infants

far outweigh any risks

Further research with fortified breast milk in

hospital and post-discharge is essential

Monitoring of infant feeding during infancy is

encouraged exclusive BF for 6 months

Maternal benefits to breast feeding

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Maternal benefits to breast-feeding

q Positive health benefits post-partum,

lower risk of breast and ovarian cancer

q Promotes maternal-infant attachment,

improves sense of self-esteem and

success with mothering

Labbok 1999

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Breast-feeding:

Recommendations

Canadian & American guidelines for

b t f di t i f t

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breast-feeding preterm infants

First choice is mothers milk

Fortification of human milk until breast-

feeding is effective

Exclusive breast-feeding until age 4-6

months CA

Longer duration if possible and desired

Pediatrics 2005; 115:496-506

Challenges in breast-feeding

t i f t

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premature infants

BF a VLBW infant is a challenging and exhaustingexperience for the mother who is undergoing

considerable stress due to worries about her infant,

separation and isolation.

Infant support non-nutritive sucking and oral

stimulation in NICU has resulted in earlier initiation of

BF, earlier discharge Rocha07 and increased BF

rates after discharge Pimenta08

Kangaroo care may promotebreast-feeding

Breast-feeding in NICU

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Breast feeding in NICU

qAssume that all women will breast-feed

q Encourage breast milk expression soon after

delivery and provide advice re collecting and

transporting BM from home to NICU

q Skin-to-skin contact facilitates increase volume

q Continued breast-feeding encouragement and

advice in NICU and post- discharge


Human donor milk banks

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q WHO recommendation 1980: human milk banks

should be made available to supply high-risk

infants when mothers milk is unavailable.

qWhen donor milk is pasteurized, it effectively

inactivates HIV and other infections, but still

retains immunological properties

q

Benefits of donor milk banks outweigh the costs

Wight. J Perinatology, 2001; 21:249-54

Metabolic syndrome

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q

Infants fed HM vs PTF had lower growth in neonatalperiod

qHowever, there were lower rates of obesity,

hypertension and leptin and insulin resistanceqTherefore, the goal should be to promote careful

nutrition support but not excessive growth or nutrient

intake

Lucas 2005; Singhal 2001, 2002, 2003

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