Iron requirements of the preterm infant

Overview

Preterm infants miss out on the late stages of pregnancy, during which their nutrient stores are established. This can often result in nutritional deficiencies, with low iron in infants being particularly common in this cohort.¹ Iron deficiency (ID) is the most common micronutrient deficiency globally.²

Iron is present in all cells within the body and serves several vital functions. It is an essential component of haemoglobin and myoglobin, contributing to the transportation and storage of oxygen. Iron is bound and transported in the body via transferrin and stored in ferritin molecules. It is involved in cellular functions that help regulate processes including cell division and oxidative metabolism, therefore adequate iron status is critical for growth and development.³ Research has shown an association between iron deficiency anaemia and impaired psychomotor and cognitive development in infants and young children.⁴

The third trimester of pregnancy is a period of rapid fetal iron accumulation. Preterm infants miss out on this time in utero and therefore have lower iron stores than term infants, increasing their risk of iron deficiency.¹ Low iron stores are often further depleted by frequent blood sampling as part of their neonatal care alongside the rapid postnatal growth these infants undergo.¹ Iron deficiency in infants, defined as decreased ferritin (<12 µg/l), is associated with inadequate dietary iron intake during the first year of life and occurs in 25–85% of preterm infants.^1,5,6 This article focuses on the importance of meeting iron requirements for infants during the neonatal period and how adequate iron supplementation in infants can be given via different methods of feeding.

Why iron supplementation is important in preterm infants

Preterm infants iron requirements are higher than term infants due to phlebotomy losses during the neonatal period and rapid postnatal growth.⁷ Inadequate iron intake can result in ID which, during infancy can lead to anaemia and reduced neurodevelopment.⁸ The age of six-months to two-years is a rapid period of growth, resulting in iron requirements per kilogram body weight being higher than during any other period of life.⁹ Iron balance needs to be carefully considered during infancy. In contrast to most other nutrients, there is no mechanism for regulated iron excretion. Excessive iron supplementation during infancy can cause poor growth and disturbed absorption or metabolism of other minerals.⁸

When is iron supplementation indicated?

Low birthweight, prematurity and early cord clamping are common risk factors for ID in infancy.¹ Iron supplementation in infants is recommended for the following:^8,10

• Preterm infants (born before 37 weeks' gestation)

• Infants who are born greater than 37 weeks' gestation with low birth weight (weighing less than 2500g at birth).

• Infants who receive erythropoietin treatment or who have had significant, uncompensated blood losses.

There is insufficient evidence to support iron supplementation within term, healthy infants and of normal birth weight.⁶

Late onset and incorrect doses of enteral iron supplementation in preterm infants can further worsen the risk of iron deficiency. ID rates are greater at six months of age when iron supplementation is delayed until two months of age.³

The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) recommend that prophylactic iron supplementation should be started at two to six weeks of age or two to four weeks of age in infants with extremely-low-birth-weight (<1800g).⁴

How much and for how long

The following iron supplementation doses are recommended:^8,10

• 2 to 3mg per kg per day during the first six months of life for preterm infants with birth weights < 1800g.

• 1–2 mg per kg per day during the first six months of age for preterm infants with birth weights of 2000–2500g.

Practical considerations

ESPGHAN strongly endorses expressed breast milk (EBM) as the preferred method of feeding for all preterm babies, however this alone is unlikely to meet the nutrient needs of very preterm babies.¹ Breast milk fortifier (BMF) is sometimes used on neonatal units to fortify BM with additional nutrients.¹ Preterm infants fed with EBM containing BMF have previously required additional iron supplementation, however SMA^® Gold Prem Breast Milk Fortifier is the first BMF to be fortified with iron in the UK and Ireland.¹¹ When mixed with preterm breastmilk, Gold Prem BMF contains 1.89mg iron per 100mls, which eliminates the need for additional iron supplementation.^11,12 This will undoubtedly lead to cost savings and reduced nursing time. It is important to note that BMF is limited to hospital use only.¹³

If the use of EBM is not possible, preterm formulas are used which have been designed to meet the unique nutritional needs of preterm infants. Preterm formulas including SMA^® Gold Prem 1 comply with ESPGHAN guidelines and are suitable from birth for preterm infants < 1800g. These formulas are fortified with iron (1.63mg per 100mls) to help meet preterm infant’s raised requirements without the need for additional iron supplementation. These preterm formulas are limited to hospital use only.

When preterm infants are discharged home, it is important to continue with iron supplementation to reduce the risk of developing ID during infancy.⁷ Post discharge preterm formulas are available to help meet preterm infants' unique nutritional requirements; however, these can contain varying levels of iron, therefore iron supplementation may still be required.¹⁴ If an infant is mixed feeding (breastfeeding and preterm formula), iron supplementation is recommended.¹⁰ The British National Formulary (BNF) advises a prophylactic dose of sodium feredetate (oral iron supplementation) at 1 mL daily for preterm infants of low birth-weight who are solely breast-fed. It is advised to commence supplementation at around four to six weeks and continued until mixed feeding is established.¹⁵ Although iron preparations are best absorbed on an empty stomach, they can be taken after food to reduce gastro-intestinal side-effects.¹⁵

Summary

Infant iron supplementation needs to be carefully managed in clinical practice as iron deficiency during this rapid period of growth can have long-term effects on cognitive function which cannot be reversed.¹⁰ Preterm infants and infants weighing less than 2500g or infants with uncompensated blood losses should all be given prophylactic iron supplementation commencing between two-six weeks after birth.^4-7 Birthweight will determine the format, dose and timeframe for iron supplementation.