One of the biggest struggles we have in the NICU is the encouragement of feeding as early as possible, as quickly as possible and as safely as possible to avoid growth failure, bowel morbidities and the psychomotor complications associated with these impairments. Inherent in their immaturity, preterm infants are born with often times quite significant gut dysmotility.
This includes the stomach and the small and large intestines. The preterm bowel is just beginning to construct appropriate motor and neural development to attain function we normally would attribute to the bowel of the term infant. We know now that early feeding is better than delaying feedings as the gut is primed to accommodate fluid and nutrients and adapt as nutrients interact with the large surface area of the gut, plus the largest immune and nervous system of the body. Remember that the in utero experience can involve swallowing up to 200 mL/kg/day of fluid. The challenge however rests on achieving the most efficient, practical and safe way to get there. In this blog I want to share some of my perspectives on this area.
How fast can we feed?
In the past neonatologists were extremely cautious, often taking weeks to decide when the correct time to start feed was. With uncorrected surfactant deficiency I can only imagine how difficult it must have been to treat these infants, albeit much larger than the smallest we have to deal with now. We recently graduated a 320 and 400 gram infants which now present a newer type of challenge as their gut and other organ systems are even more immature. It seems sub 500 gram infants are now part of our everyday challenge. I have talked at exhaustion to people on the need to standardize the feeding practice to eliminate too fast and too slow feeding. Certainly the evidence supports no negative effects from standardizing and the windfall may be faster feeding benchmarks with reduced morbidity.
Can we make the gut move faster or accelerate in maturity?
The lack of a suitable motility agent for the intestine is definitely part of the problem in managing the preterm gut. Some institutions have settled on using erythromycin which is an analog to a gut hormone called motilin but this puts infants at risk of antibiotic resistance and pyloric stenosis. Metoclopramide has been used excessively in the past and is virtually off the shelf now. I must admit that I permit some infants with persistent gastric emptying problems (i.e. gastric residuals in the absence of any other ominous signs) for a 5-day course of metoclopramide since there is some data on this. Perhaps the best and most intuitive way to get the gut moving is to just feed their gut.
The stomach is a silly organ in the preterm infant. Way too frequently it is holding up enteral feeds with the presence of gastric residuals that mostly only reflect a dysmotility problem of the stomach that may or may not be associated with intestinal dysfunction.
The stomach empties faster with plain old unfortified breast milk. It is not entirely clear how breast milk that contains both casein and whey can remain less solidified after acidification. The end result is that human milk feeding is quicker to empty out of the stomach. Feeding formula is slower to exit out of the stomach and therefore more prone to residual formation. For this and many reasons formula should no longer be offered to preterm infants in the NICU as their initial feeds until they are safely out of the morbidity window for necrotizing enterocolitis (NEC) which is around 34 weeks. The evidence is now compelling to make human milk standard of care in our everyday practice.
Moving the poo-poo train
Another simple strategy to get motility kickstarted is to stimulate the gut from the bottom end. The sight of transition stools is a good marker of the elimination of meconium and forward intestinal movement. Meconium is a viscous mixture of intestinal epithelial cells, lanugo, mucus, amniotic fluid, bile and water. It has a tendency to become very hard if dehydrated as we know all too well in conditions that predispose to inspissation of meconium such as cystic fibrosis. This disease is often accompanied by meconium ileum and/or meconium peritonitis with bowel perforation resulting from the obstruction, distension and sometimes perforation of bowel due directly from the dehydration and hardening of meconium. Being able to evacuate most of the meconium early in life may be a decided advantage for feeding and morbidity.
The potential downside to not moving meconium?
I have seen several cases of meconium inspissation where preterm infants were severely dehydrated during the first few days of life. The slow passage of stool coupled with a combination of advancing feeds and early transition to CPAP or nasal ventilation is a perfect storm for gas trapping in the gut. Any excess gas that may enter the stomach can lead to gut dilatation that can quickly compromise the intestinal barrier, particularly if thick meconium holds things up. If you have ever seen the thinness and fragility of preterm intestine in an open laparotomy you will fully understand what I mean here. Preterm intestine cannot take too much stretch before it is susceptible to bacterial translocation and/or weakening of the wall. Bacterial translocation may worsen the risk for NEC while thinning of the wally may result in propensity for spontaneous intestinal perforation (SIP). The literature does not provide good evidence that NEC is higher in those that start off on CPAP, but it is a potential risk.
Can we feed really fast?
The fastest safe feeding protocols for preterm infants stand at an advancement of about 35 mL/kg/day.1 Typically we would be confident that water requirements are met with enteral feeds of greater than 120 mL/kg/day. At the fastest rate, this would mean one could be free of TPN by 4 days. In Japan apparently they have been practicing such rapid feeding protocols and getting infants to full feeds in a week or so with accompanying low NEC rates, helped with the use of glycerin enemas. Our SPIN (www.spinprogram.ucsd.edu) feeding protocols called individualized enteral advancement tables (or iEAT) were developed with the understanding that the extremely premature gut tolerated feeding advancement at slower rates than older preterm infants and are tiered to deliver feeds in a linear manner with anywhere from 8 to 20 mL/kg/day. Most units I know settle between 15-20 mL/kg/day for all comers.
With the success of our program in reducing NEC, the challenge forward is to see if we can push the feeding rate faster.
One possible strategy could be the use of glycerin enemas (GE). Most units have some practice of using glycerin as a laxative for the preterm failure to pass stool. Most places have kept with glycerin suppositories but these can be quite large for the smallest infants. Others such as in our SPIN program have resorted to using liquid glycerin as an enema. This is passed into the rectum using a small 5Fr feeding tube inserted to about 2 cm. The volume of GE has not been standardized or tested rigorously. A Korean study showed very positive effects using 1 mL/kg/dose of 25% glycerin in water given every 12 to 24 hours to a cohort of preterm infants.2 They achieved faster time to full feeds, faster passage of meconium, lower sepsis rates, without an increase in NEC. Administration of GE is almost always accompanied by passage of stool. Sometimes the amount is small but the efficacy of passing some stool is very high. Anecdotally it is well over 90%. Obviously the use of GE needs to be tested in larger studies to demonstrate its value but it is something that may greatly assist forward flow of stool.
Making a case for the poo-poo train
The benefits of faster enteral feeds potentially includes earlier time to return to birthweight, reduced PN duration and thereby reduced central line days, reduced central line associated blood stream infection (CLABSI) rates. Reduction of growth impairment has long-term benefits on neurodevelopment. Somehow I think in this case the power of moving the poo-poo train is currently being underestimated. Maybe it is a California thing to having enemas for better health but moving the poo-poo train could be just one simple practice that can help our vulnerable infants get to full feeds with little downsides. So, here’s to pushing forward on the poo-poo train!
1. Morgan, J., Young, L., & McGuire, W. (2013). Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev, 3, CD001241. doi: 10.1002/14651858.CD001241.pub4
2. Shim, S. Y., Kim, H. S., Kim, D. H., Kim, E. K., Son, D. W., Kim, B. I., & Choi, J. H. (2007). Induction of early meconium evacuation promotes feeding tolerance in very low birth weight infants. Neonatology, 92(1), 67-72.