Nottingham Neonatal Service Clinical Guideline D5

Title: Vitamin supplementation in pre-term infants

Version: 7
Ratification April 2016
Date:
Review Date: April 2019
Approval: Nottingham Neonatal Service Clinical Guideline Group
20th April 2016
Author: Chris Jarvis
Job Title: Specialist Neonatal Dietitian
Consultation: Dr Shalini Ojha, Consultant Neonatologist, Nottingham
Neonatal Service Staff and Clinical Guideline Meeting
Guideline Chris Jarvis, Specialist Neonatal Dietitian c/o Stephanie
Contact Tyrrell, Nottingham Neonatal Service
stephanie.tyrrell@nuh.nhs.uk
Distribution: Nottingham Neonatal Service, Neonatal Intensive Care Units
Target Staff of the Nottingham Neonatal Service
audience:
Patients to Patients of the Nottingham Neonatal Service who fit the
whom this inclusion criteria of the guideline below
applies:
Key Words: Iron supplementation, preterm infant
Risk Managed: Appropriate vitamin supplementation

Evidence used: The contemporary evidence base has been used to develop
this guideline. References to studies utilised in the
preparation of this guideline are given at its end.

Clinical guidelines are guidelines only. The interpretation and application of

clinical guidelines remain the responsibility of the individual clinician. If in
doubt, contact a senior colleague. Caution is advised when using guidelines
after the review date. This guideline has been registered with the Nottingham
University Hospitals NHS Trust.

1 Background

Vitamins are a group of organic compounds that are an essential part of the diet as they cannot be
produced by the body. There are 13 vitamins commonly divided into two groups:

Fat soluble: A, D, E and K

Water soluble: thiamin (B1), riboflavin (B2), nicotinic acid (B3), pyridoxine (B6), B12, C,
folic acid, pantothenic acid, biotin

The preterm infant has higher requirements for most vitamins following premature delivery at a
time of massive accretion of all nutrients resulting in low body stores, also lower absorption and
immature enzyme transport systems.

The evidence base for exact requirements of vitamins is limited and actual quantities required are
very small in comparison to macronutrients such as protein, fat and carbohydrate. However, they
are essential to the basic processes of life and should not be forgotten.

Water soluble vitamins are not stored in the body so a continued intake is required to prevent
deficiency. Excesses are thought to be excreted in the urine, other than B12 which is excreted in
bile. Fat soluble vitamins are stored and not excreted so toxicity can be a problem.
Nottingham Neonatal Service Clinical Guideline D5

The vitamins that have been most studied in preterm nutrition are briefly discussed:

Vitamin A is a group of fat soluble compounds used by the body for regulation and promotion of
growth and differentiation of cells, including the retina of the eye and cells that line the lung.
Preterm infants have low vitamin A levels at birth and at discharge.[1] It is possible that additional
vitamin A may reduce complications of prematurity this is the subject of a Cochrane review. [2]
Recent recommendations for the preterm infant suggest an oral range of 1330-3660 iu/kg/day
while on the neonatal unit. [3, 4] Requirements after discharge are largely unknown though low
plasma levels can persist for many months in infants discharged breast feeding or on term
formulas [5] even when supplemented with 3,000iu per day. [6] A review of vitamin A in preterm
infants is available. [7]

Vitamin D is required for intestinal absorption of bone minerals - calcium and phosphate. Evidence
suggests that maternal status is more likely to affect vitamin D stores in the preterm infant than
gestation and that there is no advantage to large doses of vitamin D, as it is an adequate supply of
bone minerals that is the limiting factor. Preterm infants are able to hydroxylate dietary vitamin D
so do not need the active form. Most studies comparing different doses of vitamin D would confirm
that 400 iu/day is sufficient in the presence of adequate calcium, phosphorus and magnesium. The
latest international recommendations reflect this, but if stores are likely to be low due to poor
maternal status, 1000 iu/day is advised. [4, 8]

Vitamin D requirement is usually expressed in units per day unlike most other nutrients.

Vitamin E is a biological antioxidant that prevents haemolytic anaemia and may protect against
bronchopulmonary dysplasia, retinopathy of prematurity, though increased risk of sepsis is
reported. Minimum requirements are met from human and formula milk and there is little evidence
to support further routine supplementation.[9]

Vitamin K is given routinely at birth to all infants to prevent haemorrhagic disease of the newborn.
Human milk is very low in vitamin K so infants fed unsupplemented breast milk should receive
multiple doses of vitamin K if given enterally.

B vitamin requirements are related either to protein or energy intake and are likely to be higher in
preterm infants, though most are likely to be met from milks.

Folate deficiency may be expected in the preterm infant because of poor intrauterine stores and
rapid growth so it is added to breast milk fortifiers and LBW formulas. Unfortified milk contains
about 5ug/100ml, so when used for preterm infants will not meet current recommendations of 35-
100mcg/kg. [4, 10]

Vitamin B12 stores in the liver correlate with gestational age so are likely to be low in preterm
infants. However, low levels have not been reported in preterm infants fed human milk so
recommendations are based on the amount provided by human milk.

Vitamin C is not stored to any extent but both human milk and infant formulas are a good source
and should meet requirements, though it is usually provided as a component of the vitamin
preparations used as a source of vitamin A & D.

2 Patient Group/Indications

Vitamins should be given to all preterm infants <34 weeks gestation once on full enteral feeds
according to the milk they are receiving and the management recommendations in section 3.
Nottingham Neonatal Service Clinical Guideline D5

3 Management

Three products exist (see Table 1) but Abidec has been chosen due to the lower vitamin A than
Dalivit and poor availability of Healthy Start Vitamins in the community, which would require a
change at discharge.

Infants born <34 weeks gestation should receive a daily dose of vitamins as suggested
below:

3.1 On neonatal unit (Error! Reference source not found.):

Unfortified breast milk 0.6ml Abidec

EBM + fortifier }
Nutriprem 1 }
SMA Gold Prem Pro } 0.3ml Abidec
Term formulas }
Specialised term formulas }

If BMF is not to be used in a baby <34w gestation at birth 50micrograms folic acid should
be prescribed until discharge, though not to babies in the days prior to starting BMF.

3.2 At discharge: until 1st birthday

Breast-feeding 0.6ml Abidec once daily
Nutriprem 2 No vitamin supplementation
Normal infant formula 0.3ml Abidec once daily

Where infants are receiving breast milk and formula, for example EBM and Nutriprem 1 or breast
feeding and Nutriprem 2, a pragmatic decision based on proportion of each should be made. If
uncertain seek dietetic advice or err on the side of caution and prescribe the higher level.

3.3 Infants with Conjugated Jaundice

Infants with conjugated jaundice an ongoing conjugated bilirubin >50micromol/l (not as soon as
the level reaches 50) may require an increase in fat soluble vitamins due to possible malabsorption
of fat. The following daily doses offer a practical option for providing additional fat soluble vitamins:

0.6ml Dalivit 5000iu Vitamin A, 400 iu Vitamin D

50mg Vitamin E 50iu Vitamin E*
1mg Vitamin K**

*Vit E is provided as alpha-tocopheryl acetate suspension

**Vit K will be prescribed as phytomenadione until discharge (or transfer to paediatric
gastroenterology if applicable) when it would be changed to menadiol

Other vitamin supplements should be stopped and replaced with the above and continued
until liver function has returned to normal.
Nottingham Neonatal Service Clinical Guideline D5

3.4 After discharge

Infants having Nutriprem 2 will change to a follow on milk or term formula by 6 months corrected
gestational age when GPs should have stopped prescribing Nutriprem 2. At this stage they should
be prescribed 0.3ml Abidec daily until their 1st birthday. Thereafter parents should follow UK
Department of Health advice (See Section 6) for all babies.

Healthy Start Vitamin drops are not prescribable in the community. Nor are they readily
available in health centres other than free of charge to families eligible for the Healthy Start
Scheme. At home infants requiring vitamins who are not eligible for free Healthy Start
vitamins should get Abidec on prescription from the GP until 1st birthday.

These recommendations aim to meet currently known recommendations for vitamins in

preterm infants within a practical framework for day to day use. Any change to formulas or
fortifiers currently in use may necessitate a review of this policy.

4 Audit points

All babies born at <34 weeks gestation

on unfortified EBM receive 0.6ml Abidec
on fortified EBM, Nutriprem 1 or term formula receive 0.3ml Abidec daily
changed onto Nutriprem 2 have vitamin supplementation stopped
discharged breast feeding receive 0.6ml Abidec daily
discharged on term formulas receive 0.3ml Abidec daily

5 Allied Guidelines

D4 - Enteral Feeding
D6 - Neonatal Parenteral Nutrition
D7A - Breast Milk Fortification
D8 - Iron supplementation in Preterm Infants
D10 Feeding Babies with Neonatal Surgical Problems

6 Department of Health vitamin recommendations for term infants

This guideline is intended for infants born less than 34weeks gestation. Mothers of infants born
between 34-<37 weeks should be advised to start vitamins as for those infants where mothers
vitamin status in pregnancy is in doubt see below.

The UK Department of Health recommends a daily dose of vitamins A, C and D for:

breastfed infants from 6 months (or from 1 month if there is any doubt about the
mothers vitamin status during pregnancy)
formula-fed infants over 6 months and taking less than 500 ml infant formula per day
children under 5 years of age

This is particularly important for children who are fussy eaters, those of Asian, African, Afro-
Caribbean or Middle Eastern origin or living in northern areas of the UK. [11, 12]

Healthy Start Vitamin Drops are currently only available to those eligible for the Healthy Start
Scheme, unless local arrangements have been made as in Nottingham City where all babies
receive them free of charge. Otherwise, Abidec is the most similar alternative available from most
chemists and supermarkets.
Nottingham Neonatal Service Clinical Guideline D5

Table 1 Composition of Available Multivitamin Preparations

Vit A Vit D Vit C Vit B1 Vit B2 Nic Acid Vit B6
Abidec
0.3ml 666 iu 200 iu 20 mg 0.2 mg 0.4 mg 4.0 mg 0.4 mg
0.6ml 1333 iu 400 iu 40 mg 0.4 mg 0.8 mg 8.0 mg 0.8 mg
Dalivit
0.3ml 2500 iu 200 iu 25 mg 0.5 mg 0.2 mg 2.5 mg 0.25 mg
0.6ml 5000 iu 400 iu 50 mg 1.0 mg 0.4 mg 5.0 mg 0.5 mg
Healthy
Start
5 drops 660 iu 280 iu 20 mg
10 drops 1320 iu 560 iu 40 mg

7 Appendix

1. Algorithm of Vitamin Supplementation

A combined algorithm of iron and vitamin supplementation is also available for use as an aide
memoire on the neonatal unit
Nottingham Neonatal Service Clinical Guideline D5

8 Bibliography

1. Mactier, H., et al., Inadequacy of IV vitamin A supplementation of extremely preterm

infants? The Journal of Pediatrics, 2005. 146(6): p. 846-847.
2. Darlow, B.A. and P.J. Graham, Vitamin A supplementation to prevent mortality and short-
and long-term morbidity in very low birthweight infants. Cochrane Database of Systematic
Reviews, 2011(10): p. CD000501.
3. Koletzko, B., B. Poindexter, and R. Uauy, eds. Nutritional Care of Preterm Infants: Scientific
Basis and Practical Guidelines. Vol. 110. 2014, Karger.
4. ESPGHAN, et al., Enteral nutrient supply for preterm infants. Journal of Pediatric
Gastroenterology & Nutrition, 2010. 50: p. 1-9.
5. Peeples, J.M., et al., Vitamin A status of preterm infants during infancy. American Journal of
Clinical Nutrition, 1991. 53(6): p. 1455-1459.
6. Delvin, E.E., et al., Oral Vitamin A, E and D Supplementation of Pre-Term Newborns either
Breast-Fed or Formula-Fed: a 3-Month Longitudinal Study. Journal of Pediatric
Gastroenterology and Nutrition, 2005. 40(1): p. 43-47.
7. Mactier, H., Vitamin A for preterm infants; where are we now? Semin Fetal Neonatal Med,
2013.
8. Mimouni, F.B., D. Mandel, and R. Lubetzky, Calcium, phosphorus, magnesium and vitamin
D requirements of the preterm infant, in Nutritional Care of Preterm Infants: Scientific Basis
and Practical Guidelines, B. Koletzko, B. Poindexter, and R. Uauy, Editors. 2014, Karger. p.
146-147.
9. Brion, L.P., E.F. Bell, and T.S. Raghuveer, Vitamin E supplementation for prevention of
morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews,
2003(4): p. CD003665.
10. Leaf, A. and Z. Lansdowne, Vitamins - conventional uses and new insights, in Nutritional
Care of Preterm Infants: Scientific Basis and Practical Guidelines, B. Koletzko, B.
Poindexter, and R. Uauy, Editors. 2014, Karger. p. 153-166.
11. Dept of Health, Weaning and The Weaning Diet, Report on Health and Social Subjects 45.
1994, Stationery Office.
12. NICE, Public Health Guidance - PH11 - Maternal and Child Nutrition. 2008.
https://www.nice.org.uk/guidance/ph11
Nottingham Neonatal Service Clinical Guideline D5
Appendix 1 Algorithm