Dear Editor

I read with great interest the article of Fang et al, who investigated the relationship between mesenteric response to feeding and feeding tolerance in preterm infants [1]. In a comparable population, we reported that the significant increase in velocity in the superior mesenteric artery after a first feed given during the first week of life was not influenced by perinatal acute asphyxia, gestational age, intrauterine growth retardation, early post-natal respiratory distress or hypotension [2]. In our small cohort, good tolerance to enteral feeds during the first weeks of life was associated with a greater rise in end diastolic velocity, which is close to the authors' observation of a positive correlation between early tolerance to enteral feeds and a lower index of vascular resistance after the test feed. Two questions nevertheless seem important: Is a single Doppler measurement of superior mesenteric artery blood flow sufficient to determine when to feed a "high risk" preterm infant? And which criteria define the "high risk" infant? As mentioned by Martinussen et al. [3], preterm infants require a systemic circulatory adaptation to allow postprandial mesenteric hyperemia, with an increase in cardiac output and a decrease in blood pressure. The circumstances associated with hemodynamic instability, as in sepsis, or elevated baseline cardiac output, as in ductal steal, could thus compromise the circulatory response to feeding and lead to intolerance. In our population, we tested numerous biodemographic and clinical factors suggested by previous research [4], but also a more than 30% increase in mesenteric diastolic velocity 30 min after a test feed of 4 ml/kg of human milk, for their relationship to feeding tolerance during the first three weeks of life. This multilinear regression analysis revealed the significant positive influence of antenatal steroids and the negative influences of significant ductus arteriosus, nosocomial infection, and prolonged ventilatory dependency. The result of the mesenteric profile after the test feed, however, was not included in the final model. We thus believe that a single examination of superior mesenteric artery blood flow velocities after a first feed at the third postnatal day - as suggested by the authors - is probably insufficient to predict mean term feeding tolerance and should instead be integrated into a more complete evaluation of the patient's hemodynamic status. We personally recommend serial evaluations in cases of ductus persistence or reopening and before enteral feeding resumption after significant gut disease.

Gilles Cambonie
Neonatal Intensive Care Unit, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, France.

References
(1) Fang S, Kempley ST, Gamsu HR. Prediction of early tolerance to enteral feeding in preterm infants by measurement of superior mesenteric artery blood flow velocity. Arch Dis Child Fetal Neonatal Ed 2001; 85: F42-5.
(2) Cambonie G, Luc F, Montoya F, Sarda P, Rieu D. Mesenteric blood flow in premature infants. Pediatr Res 1996; 40: 522 (A 46).
(3) Martinussen M, Brubakk AM, Vik T, Yao AC. Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants. Pediatr Res 1996; 39: 275 -80.
(4) Slagle TA, Gross SJ. Effect of early low-volume enteral substrate on subsequent feeding tolerance in very low birth weight infants. J Pediatr 1988; 113: 526-31.

Dear Editor,

We thank Drs Pezzati et al for their interest in our paper. We agree that there are many different factors, which will affect the mesenteric blood flow response to feeding.

We stated that “the study did not set out to compare the response of SGA and AGA infants to enteral feeds” because of the following:
1.  The study was not powered to detect differences between SGA and AGA infants.
2.  The SGA infants with normal growth velocity were not differentiated from the growth restricted infants antenatally. It is likely that more severe anomalies of perfusion will be encountered in those SGA infants who had abnormal antenatal Doppler findings [1,2].

It should be noted that in our study, infants were not studied on the first day of life. SMA Blood flow velocity measurements were taken between 2 and 30 days of age [3]. Previous work showed that in SGA infants, baseline SMA-BFV is reduced on the first day of postnatal life and increased during the first week [1,2]. In contrast Drs Pezzati et al enrolled babies on the first day of life. At this stage, a lower baseline SMA-BFV would be expected [2]. However, we would be interested to know whether they observed a different change from baseline velocity in the SGA infants. Otherwise, the differences they observed may be related to the lower baseline values.

We agree with the Drs Pezzati et al that further studies are necessary for SGA infants.

Dr Swee Fang
Homerton Hospital

Dr Steve T. Kempley
Royal London Hospital

Professor Harold R. Gamsu
King's College Hospital

References:
(1) Gamsu HR, Kempley ST. Enteral hypoxia/ischaemia and necrotizing enterocolitis. Seminars in Neonatology 1997; 2: 245-54
(2) Kempley ST, Gamsu HR, Vyas S, Nicolaides K. Effects of Intrauterine Growth Retardation on Postnatal Visceral and Cerebral Blood Flow Velocity. Arch Dis Child 1991; 66: 1115-8
(3) Fang S, Kempley ST, Gamsu HR. Prediction of early tolerance to enteral feeding in preterm infants by measurement of superior mesenteric artery blood flow velocity. Arch Dis Child 2001; 85: F42-5

Dear Editor,

We read with interest the study on the prediction of early tolerance to enteral feeding in preterm infants reported by Fang et al.[1]. We believe that this is a very important report for its clinical implications. We do, however have several questions. The Authors did not find "difference in superior mesenteric artery (SMA) blood flow velocity and in the response to enteral feeds between SGA and AGA infants". We have recently concluded a study evaluating the effect of early enteral feeding on SMA blood flow velocity in SGA and AGA infants. After informed parental consent we evaluated 40 healthy preterm neonates with less than 34 weeks, respectively divided in two groups of 20 AGA and 20 SGA infants. All of the infants were enrolled in the first day of life once they were stable. With the use of Doppler color ultrasonography, blood flow velocities and resistance index in the SMA were measured both preprandially and postprandially. For all the neonaes test feeding consisted of 2ml breast milk administered through the nasogastric tube. After the preprandial measurement, the milk was given, and postprandial measurements of SMA blood flow velocity were registered at 30 minute intervals for 120 minutes. Regarding preprandial measurements, our data confirms previous studies [2] but contradicts the findings of Fang et al. [1], which show that the SMA velocities are lower in SGA infants when compared to AGA infants. Furthermore, we found significant differences in the postprandial values of mean velocity, systolic velocity and resistance index between the two study groups. We believe that the differences between our study and Fang's study may be principally attributed to the fact that the Fang study "did not set out to compare the response of SGA or AGA infants to enteral feeds". In addition please note that discrepance in results may also be due to the difference in the day of the test feed, the amount of the milk and the type of milk that can differently affect intestinal blood flow [3,4]. In conclusion, this is a very important study for the clinician in deciding whether high risk preterm AGA infants could tolerate enteral feeds. On the contrary, we think that further dedicated studies are necessary for correctly evaluating the SMA haemodynamic response to enteral feeding in SGA preterm infants.

References
(1) Fang S, Kempley ST, Gamsu HR. Prediction of early tolerance to enteral feeding in preterm infants by measurement of superior mesenteric artery blood flow velocity. Arch Dis Child Fetal Neonatal Ed 2001;85:F42-F45.
(2) Kempley ST, Gamsu HR, Vyas s, et al. Effects of intrauterine growth retardation on postnatal visceral and cerebral blood flow velocity. Arch Dis Child 191;65:115-118.
(3) Qamar MI, Read AE, Mountford R. Increased superior mesenteric artery blood flow after glucose but not lactulose ingestion. QJM 1986;60:893-896.
(4) Coombs RC, Morgan MEI, Durbin GM, et al. Doppler assessment of human neonatal gut blood flow velocities: postnatal adaptation and response to feeds. J Pediatr Gastroneterol Nutr 1992;15:6-12.

We read the recent article by Fang et al on prediction of early tolerance to enteral feeds in neonates by measuring superior mesenteric artery (SMA) blood flow velocity. [1] Almost half of the neonates with poor vasomotor response to feeding developed feed intolerance, and subsequently sepsis. There was no significant difference in the mean preprandial SMA velocity between neonates who did and those who did not show a rise in postprandial SMA velocity. It is important to appreciate that the optimal/normal SMA velocity will be different for different neonates at varying postnatal ages. It is quite possible that the gut flow was suboptimal in neonates who did not show a rise in postprandial SMA velocity and subsequently developed feed intolerance and sepsis. Continued enteral feeds in absence of "clinical" signs of feed intolerance may thus have led to precipitation/exacerbation of gut mucosal injury followed by translocation of enteric organisms and sepsis. There is increasing evidence that nosocomial infections are caused by translocation of enteric microorganisms. [2] Endotoxemia and sepsis impair mesenteric perfusion and cause organ dysfunction and exacerbations of polymicrobial bacteremia due to intestinal mucosal leakage. [3] Increased SMA velocity has been reported in neonates with necrotising enterocolitis (NEC), suggesting that total gut ischemia is not present at the time when the disease is clinically apparent but may precede the onset of symptoms. [4] As early as the first day of postnatal life, infected neonates are shown to have splanchnic hyperaemia, indicating the role of systemic inflammatory response. [5] The relationship between gut integrity, feed intolerance, sepsis, and pathogenesis of NEC though complex, has significant clinical implications. Stopping enteral feeds for 48 hours may thus be a safe option in high-risk neonates with suspected/culture positive sepsis to avoid consequences of bacteremia even if they are "tolerating feeds well".[6]

Patole Sanjay
Jog Sunila
Whitehall JS

References: (1) Fang S, Kempley ST, Gamsu HR. Prediction of early tolerance to enteral feeding in preterm infants by measurement of superior mesenteric artery blood flow velocity. Arch Dis Child Fetal Neonatal Ed 2001; 85: F42-F45.
(2) Sileri P, Sica GS, Rastellini C et al. Bacterial translocation and its surgical implications. G Chir 1999; 20(10): 440-44.
(3) Sam II AD, Sharma AC, Law WR, Ferguson JL. Splanchnic vascular control during sepsis and endotoxemia. Front Biosci 1997; 2: E72-E92.
(4) Kempley ST, Gamsu HR. Superior mesenteric artery blood flow velocity in necrotising enterocolitis. Arch Dis Child 1992; 67: 793-96.
(5) Kempley ST, Murdoch E. splanchnic haemodynamic disturbances in perinatal sepsis. Arch Dis Child Fetal Neonatal Ed 2000; 83:F139-F142.
(6) Patole SK, Kadalraja R, Tuladhar R, Almonte R, Muller R, Whitehall JS. Benefits of a standardised feeding regimen during a clinical trial in preterm neonates. IJCP 2000; 54:429-31.