Effect on morbidity

Coutsoudis et al reported no significant impact of neonatal vitamin A supplementation on the incidence of respiratory distress in the neonatal period (RR 0.95, 95%CI 0.69 to 1.30). However, the sample size was too small to detect even moderate differences in morbidity between the groups. There was a trend towards increased hospitalization for pneumonia during the first year of life in the vitamin A group (RR 3.74, 95%CI 0.82 to 17.0). This difference was statistically not significant after adjusting for risk factors of pneumonia (P=0.19 from proportional hazards model) (192).

Humphrey et al found no effect of vitamin A supplementation on one-week period prevalence of common morbidities at 4, 6 or

12 months of age. However, between birth and

4 months of age they reported that a lower proportion of infants were brought for medical care and treatment of cough in the vitamin A group (14.2% vs. 24.6%, RR 0.58, 95%CI 0.38 to 0.87) (193).

Effect on neurodevelopment, malnutrition or other outcomes

No studies examining the effect of vitamin

A supplementation in LBW infants on neu- A supplementation in LBW infants on neu-

ies in developing country settings before this infants) and Rahmathullah et al (n = 1851

intervention can be recommended for LBW supplemented LBW infants) reported no epi-

infants.

sodes of bulging fontanelle or other neurologi- cal adverse effects associated with vitamin A

Recommendations

supplementation (192, 194). International and national organizations recommend a daily vitamin A supplementa-

Conclusions and implications tion of 700–1500 IU per kg body weight from There is paucity of evidence that the usually

birth until the infant attains 2000 g body recommended daily dose of 700–1500 IU per

weight to growing pre-term infants receiving kg body weight is efficacious in LBW infants.

human milk. Standard practice in many neo- Further, there are no data to compare large-

natal units is to provide commercially manu- dose supplementation in the first few days of

factured multivitamin preparations, which life with a small daily dose of vitamin A.

include vitamin A, to LBW infants receiving There is evidence from one study in India

unfortified human milk from birth until the that a large dose of vitamin A (50,000 IU in

infant attains 2000 g body weight. It was not one or two divided doses) during the first days

possible to provide additional recommenda- of life may have a survival advantage, particu-

tions due to insufficient evidence. larly in infants with birth weight <2000 g. This

SUMMARY TABLE 2.2.1 Effect of vitamin A supplementation on mortality

Study, Design

Approximate proportion of

(Level of Inclusion participants with gestation age a Outcome Effect measure evidence)

Comparison groups

measure [95% CI]

Infants who received 50,000 IU Mortality RR 0.74 al (193 )

Humphrey et Subgroup analysis NK

during the (0.26, 2.02) RCT (LII)

limited to infants

Vitamin A on the first day of

with birth weight

first year 1500–2499 g

life (n=101) compared with

infants who received placebo of life (n=98)

Infants who received 3 doses Mortality RR 1.07 et al (192)

Coutsoudis Gestational age

during the (0.16, 7.26) RCT (LII)

<36 weeks and

of 25,000 IU Vitamin A each

first year of 950–1700 g

birth weight

before day 10 of age (n=43)

compared with infants who

life

received placebo (n=46)

Infants who received 2 doses Mortality Overall RR 0.63 et al (194)

Rahmathullah Subgroup analysis 3%

during the (0.48, 0.83) RCT (LII)

limited to infants

of 24,000 IU Vitamin A each

with birth weight

first 6 months <2500 g

on days 1 and 2 of age

(n=1851) compared with

of life Birth weight

infants who received placebo

Birth weight 2000–2499 g RR 0.76

(0.52, 1.10) a If gestational age was not available in the publication, infants with birth weight <1500 g are assumed to be <32 wk gestation, those weighing 1501–2000 g to be 32–36 wk gestation, and those weighing 2001–2500 g to have a gestation of 37 weeks or more.

40 OPTIMAL FEEDING OF LOW-BIRTH-WEIGHT INFANTS: TECHNICAL REVIEW

VITAMIN D SUPPLEMENTATION

6 weeks postnatal age (197). At age 6 weeks, The vitamin D content of a typical oral multi-

the radiographic bone scores (median 2.0 vitamin supplement used for pre-term infants

and 2.5 in high-dose and usual dose groups, receiving human milk is 400 IU per daily

respectively) as well as the mean serum osteo- dose.

calcin concentrations were similar in the two study groups.

From 1985 to 1987 Backstrom et al rand- Results

omized 70 infants <34 weeks gestational age

Effect on mortality, morbidity and

(birth weight <2000 g) to receive vitamin D

neurodevelopment

500 IU or 1000 IU per day from the time of tol- No intervention studies were located which

erance of full enteral nutrition until 3 months examined the impact of vitamin D supple-

of age. This study had a factorial design and mentation on mortality rates, morbidity or

infants also received 108 mg/kg calcium with development in LBW infants.

53 mg/kg phosphorus or placebo. At 3 months of age the infants who received 500 IU vita-

Effect on bone mineralization

min D had a statistically significant higher No studies were located which examined the

bone mineral content than those infants who impact and clinical outcomes in infants who

received 1000 IU. The lowest bone mineral were fed unsupplemented and vitamin D-sup-

content was found in infants who received 1000 plemented human milk. Studies reporting

IU/day vitamin D and no calcium or phospho- clinical outcomes related to vitamin D sup-

rus. At 9–11 years, only 50% of infants (n=35) plementation have only involved case series

were available for follow-up; there was no dif- and were from the early 1970s. Robertson

ference in bone mineral content or bone min- reported on 25 South African pre-term infants

eral density between the infants who received of mean gestational age 31 weeks (mean birth

low or high vitamin D doses (198). weight 10 g) who were fed unsupplemented

In a later study (from May 1994 to January mother’s own milk from birth until hospital

1996), Backstrom et al randomized 39 infants discharge (173). Lucas et al reported on 45 UK

<33 weeks gestational age and gave vitamin D pre-term infants of mean gestational age 30

200 IU/kg of body weight/day (up to a maxi- weeks (mean birth weight 1050 g) fed unsup-

mum of 400 IU/day) or 960 IU/day until 3 plemented mother’s own milk from birth until

months of age. There was no difference in hospital discharge (196). In both these studies,

bone mineral content or in bone mineral den- the infants were followed from birth till hos-

sity at 3 and 6 months corrected age between pital discharge; high rates of osteopenia and

the infants who received low or high vitamin fractures in the infants fed unsupplemented

D (199).

human milk were reported. Lucas et al followed the infants further till 18 months of age

Conclusions and implications and reported that infants fed unsupplemented

There is some evidence of the need for vitamin pre-term mother’s milk had 2 cm reduction in

D supplementation of human-milk-fed infants linear growth and two infants had clinical evi-

<1500 g for adequate bone mineralization and dence of rickets.

to prevent rickets of prematurity. There seems Three studies were located which compared

to be no additional benefit of increasing the different doses of vitamin D on bone miner-

intake of vitamin D for VLBW infants from alization in human-milk-fed VLBW (very low

the usually recommended 400 IU per day. birth weight, <1500 g) infants (197–199). Evans

There are no clinical trial data on the effect of et al randomized 81 Canadian, breastfed LBW

vitamin D on key clinical outcomes in infants infants <1500 g and gave either the usual 400

with birth weight >1500 g. There are very IU dose or a high-dose (2000 international

few studies from developing countries where units (IU)) of vitamin D from 72 hours till

nutrient deficiencies may be more common.

RESULTS

42 OPTIMAL FEEDING OF LOW-BIRTH-WEIGHT INFANTS: TECHNICAL REVIEW

Effect on morbidity