Nutrition is the foundation of the rapid growth seen in the third trimester of pregnancy. During the nal twelve weeks of pregnancy, the fetus triples its body weight, undergoes rapid developmental maturation of the brain and other organs, and develops immunity. If a baby is born premature, the onus lies with the neonatologist to promote and sustain in utero growth pattern. Poor nutrition during this vulnerable period results in a signi cant impact on the growth and development of the baby. The de ciency of macronutrients result in extra-uterine growth retardation (EUGR). EUGR results in a poor neurodevelopmental outcome. The de ciency of micronutrients at critical periods of brain development result in speci c de cits, which may not be corrected even if a adequate amounts of nutrients are provided later. Poor nutrition in preterm results in signi cant decrease in brain volume, increased risk of neurological disabilities, cardio-metabolic maladaptation, lower bone mineral density, and increased risk of social disabilities.
The growth of a preterm neonate is ideal, if it follows the growth pattern of a healthy, normally growing human fetus of the same gestational age. Early “aggressive” nutrition regimens can prevent the postnatal growth failure and improve neurocognitive outcomes in a preterm neonate. Cumulative energy and protein de¬cits may lead to EUGR if an early, aggressive approach to nutrition is not adopted.
Early nutrition is specifically important for extremely preterm infants (< 28 weeks of gestation), extremely low-birth-weight (ELBW) infants, and growth-restricted neonates. A key element of the aggressive nutrition strategy is an adequate protein intake in the form of early intra venous (IV) administration of amino acids 3.8-4.2 g/kg/day in extremely preterm neonates and 3.2-3.6 g/kg/day in other preterm neonates.
The advantages include an increased rate of weight gain, reduced growth deficits, and a better weight at discharge.
For optimal growth, while on high-protein nutrition, an energy intake of around 115-120 kcal/kg/day is ideal. The initiation of lipids at 0.5-1 g/kg/day from the first day is advisable.
Colostrum painting and early “trophic” feeds with mother's expressed breast milk (EBM) can help establish the favorable gut microbiome and reduces the incidence of sepsis and necrotizing enterocolitis (NEC) in preterm neonates.
Minimal enteral nutrition (feed volumes of 10-20 mL/kg/day) helps in early colonization of favorable gut flora, reduces time to gain birth weight, improves feed tolerance, and helps in better gut motility. Early enteral feeding and rapid feed advancement with EBM has advantages, including a reduced neonatal intensive care unit (NICU) stay and reduced sepsis related to IV nutrition. The disadvantage of enteral feeding with cow's milk-based formulas is a higher risk of NEC, especially in high-risk groups like extremely preterm infants and those with compromised gut perfusion like Intrauterine growth restricted babies. Also, due to gut immaturity, preterm infants are prone to recurrent feed intolerance while on enteral feeds.
Early enteral feeding with human breast milk is recommended for earlier gut priming with favorable gut bacteria, better development of the intestinal mucosal epithelium, optimal development of the intestinal immune system, better digestive tolerance, reduced incidence of sepsis, and early discharge from the hospital without increasing the risk of NEC in a preterm neonate. We routinely practice early enteral feeding soon after birth.
A Cochrane meta-analysis that looked at slow advancement (daily increments of 10-20 mL/kg/day) versus rapid advancement (increment of 30-40 mL/kg/day) in very preterm or very low-birth-weight (VLBW) infants did not demonstrate an increased risk of NEC (RR 1.07; 95% CI 0.83-1.39) or mortality (RR 1.15; 95% CI 0.93-1.42) in the latter group. On the contrary, slow advancement led to a delay in the establishment of full enteral feeds and an increased risk of invasive infection. Thus, daily feed increments of 30-40 mL/kg/day are suggested in preterm or VLBW infants.
Yes, preterm infants can be fed EBM via a nasogastric tube while they are on a ventilator or on a CPAP support if they are hemodynamically stable. This is a routine practice at our unit as well as at many other units. Feeding is interrupted for brief periods around peri-extubation or if there are signs of feed intolerance.
It is to be emphasized that human milk or donor milk is recommended for feeding preterm neonates. If neither are available a formula closest in composition to breast milk which contains all the the nutrients as recommended by professional agencies like European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) may be used. Preterm formulas should contain higher proteins and calories to facilitate the adequate growth. Whey predominant formulas have a pro le closer to breast milk and are better tolerated. Long-chain polyunsaturated fatty acids (LCPUFAs)like omega-3 docosahexaenoic acid (DHA) and omega-6 arachidonic acid (AA) are essential for neural and retinal development in neonates and also have an impact on membrane function, eicosanoid formation, immunity and numerous physiological processes.
The DHA intake recommended by ESPGHAN committee on Nutrition for preterms is 12-30mg/kg/day and AA 18-42mg/kg/day with the ratio of AA to DHA in the range of 1-2:1 and the eicosapentenoic acid supply should not exceed 30% of DHA supply. The intake of formula containing DHA levels of 0.3% fatty acids has been shown to enhance development of visual acuity in infants at 12 months of age.
Other components like galacto - and fructo oligosaccharides (Prebiotics) may confer bifidogenic effects and may have beneficial effects on gut microbome.
Despite the use of aggressive parenteral and enteral nutrition, nearly 25% of ELBW infants have severe EUGR-defined as growth less than the third centile for a postmenstrual age (PMA). These may reflect the need for a greater protein and energy intake during the preterm period to sustain a growth of 15 g/kg/day or more. The consequences of EUGR include immediate effects of protein calorie restriction, like susceptibility to infection, hypoglycemia, hypothermia, and sepsis. Long-term effects of EUGR include adverse neurodevelopmental outcomes and a risk of obesity and programing for adult onset disease if a rapid weight gain occurs on follow-up.
Preterm infants need to be fed EBM with or without fortification as needed. If the preterm infant require formula feeds, it is best to provide a preterm formula. Preterm formulas are richer in calories and have a higher proportion of proteins, iron, zinc, and some vitamins compared with term formulas.
The evidence supports that these formulas should be continued post discharge.
The evidence shows that the use of high-calorie formula post discharge results in higher rate of weight gain. However, the benefits do not seem to be sustained upon follow-up at 12-18 months or translate into a better neurodevelopmental outcome.
At our unit, we help mothers focus on the lactation support and use a preterm formula until the baby regains its centile or the baby is back on direct breast milk or EBM. If needed, the term formula is used after the baby has completed “catch-up” growth.
In preterm infants, a delay in cord clamping provides more time for the physiological transition from a fetal to a neonatal life. A recent meta-analysis confirmed that a delay in cord clamping of 60 seconds or more was associated with a reduced hospital mortality by 30% (RR 0.68; 95% CI 0.52-0.90), an increased peak hematocrit by 2.73 (95% CI 1.94-3.52), a reduced need for blood transfusion, and an increased peak serum bilirubin by 4 mmol/L. Some studies have shown a reduction in intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD). However, the meta-analysis suggested neither an increase nor a decrease in these as well as much other morbidity.
CPAP is a relatively safe and effective tool to treat respiratory distress in term and preterm neonates from a variety of causes. Sometimes, neonates on CPAP can have complications like pneumothorax and air leaks. Like all therapeutic modalities, the judicious use provides the best outcome.
The initiation of CPAP-right in the delivery room at the very onset of respiratory distress-is a key to the reduction in respiratory morbidity, such as the need for mechanical ventilation. The termination of CPAP is determined by the resolution of the underlying illness, a reduced need for oxygen, and a sustained respiratory effort from neonates. Hence, the optimal duration of CPAP is determined by an early initiation and a prompt termination of CPAP, and varies with each neonate.
The most prudent oxygen saturation range in preterm neonates on oxygen therapy seems to be 90%-95% and hence, the alarm limits to be set are 96% for the higher limit and 89% for the lower limit. Multiple trials (eg, STOP-ROP, BOOST-II, and SUPPORT) have tried to establish the ideal saturation limits in order to provide just the right amount of oxygen to neonates to reduce the risk of retinopathy of prematurity (ROP), BPD, and neurological morbidity. A meta-analysis of these trials suggests that in the range of 85%-89%, there was an increased incidence of NEC, a higher mortality rate at 18-24 months, and a lower incidence of ROP. The STOP-ROP trial had earlier shown that peripheral oxygen saturation in the range of 96%-99% was associated with a greater incidence of BPD and a longer duration of hospitalization.