Alison Leaf

Feeding growth restricted preterm infants with abnormal antenatal Doppler results

Absence or reversal of end diastolic flow (AREDF) in the umbilical artery is associated with poor outcome, and elective premature delivery is common. Feeding these infants is a challenge. They often have poor tolerance of enteral feeding, and necrotising enterocolitis may develop. This review explores current practice to see if there is evidence on which to base guidelines. The incidence of necrotising enterocolitis is increased in infants with fetal AREDF, especially when complicated by fetal growth restriction. Abnormalities of splanchnic blood flow persist postnatally, with some recovery during the first week of life, providing justification for a delayed and careful introduction of enteral feeding. Such a policy exposes babies to the risks of parenteral nutrition, with no trials to date showing any benefit of delayed enteral nutrition. Trials are required to determine the optimum timing for introduction of enteral feeds in growth restricted infants with fetal AREDF.

Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth. METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds “early,” on day 2 after birth, or “late,” on day 6. Gradual increase in feeds was guided by a “feeding prescription” with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC. RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11–1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77–1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge. CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.

Emergency treatment of neonatal hyperammonaemic coma with mild systemic hypothermia.

An infant aged 3 days presented with hyperammonaemic coma and seizures, which were found to be a result of a urea-cycle defect. Haemofiltration, alternative pathway metabolites, and glucose and insulin failed to lower the plasma ammonia concentration below 2000 micromol/L. The infant was then cooled to a rectal temperature of 34 degrees C for 48 h and put on haemofiltration for 12 h. Plasma ammonia fell to around 100 micromol/L and remained at this concentration after haemofiltration. He roused from his coma, breathed spontaneously, and resumed bottle feeding. Hypothermia may be therapeutic in such instances of metabolic coma because it lowers the enzymatic rate of production of the toxin while non-enzymatic methods remove the toxin.

Milk osmolality: does it matter?

High osmolality of infant feed reflects a high concentration of solute particles and has been implicated as a cause of necrotising enterocolitis. Evidence for direct intestinal mucosal injury as a result of hyperosmolar feeds is scant, and no good evidence has been found to support such an association. High osmolality of enteral substrate may, however, slow down gastric emptying. Osmolality of current infant feeds ranges from around 300 mOsm/kg in human breast milk to just more than 400 mOsm/kg in fully fortified breast milk. Addition of mineral and vitamin supplements to small volumes of milk can increase osmolality significantly and should be avoided if possible.

Feeding infants below 29 weeks’ gestation with abnormal antenatal Doppler: analysis from a randomised trial

Objective To describe feeding and gastrointestinal outcomes in growth-restricted infants <29 weeks’ gestation and to determine the rate of feed advancement which they tolerate. Design Analysis of prospectively collected data from a randomised feeding trial, the Abnormal Doppler Enteral Prescription Trial (ADEPT). Setting 54 neonatal units in the UK and Ireland. Participants 404 preterm, growth-restricted infants with abnormal antenatal Doppler studies from ADEPT. 83 infants <29 weeks and 312 infants ≥29 weeks’ gestation were included in this analysis. Interventions In ADEPT, infants were randomised to start milk ‘early’ on day 2 after birth, or ‘late’ on day 6. Subsequent feed advancement followed a regimen, which should have achieved full feeds by day 16 in the early and day 20 in the late group. Main outcome measures Full feeds were achieved later in infants <29 weeks; median age 28 days {IQR 22–40} compared with 19 days {IQR 17–23} in infants ≥29 weeks (HR 0.35, 95% CI 0.3 to 0.5). The incidence of necrotising enterocolitis was also higher in this group; 32/83 (39%) compared to 32/312 (10%) in those ≥29 weeks (RR 3.7, 95% CI 2.4 to 5.7). Infants <29 weeks tolerated very little milk for the first 10 days of life and reached full feeds 9 days later than predicted from the trial regimen. Conclusions Growth-restricted infants born <29 weeks’ gestation with abnormal antenatal Doppler failed to tolerate even the careful feeding regimen of ADEPT. A slower advancement of feeds may be required for these infants. Trial registration number ISRCTN87351483.

Abnormal Doppler enteral prescription trial study: the results of a trial of feeding in a high risk group of premature babies

Background Abnormal antenatal Dopplers with intrauterine growth restriction (IUGR) are associated with increased adverse outcomes in premature infants. Anxiety about necrotising enterocolitis (NEC) often results in delay in enteral feeding. Babies of less than 35-week gestation with IUGR and abnormal antenatal Dopplers were randomised to early (24–48 h) or late (120–144 h) initiation of milk feeds, with protocol for increasing feed volume the same in both groups. Data collected included daily milk intake, evidence of gut pathology, sepsis and need for parenteral nutrition. Primary end points were days to full feeds (150 ml/kg/day) sustained for 3 days and NEC. Secondary end points included death, sepsis, growth and duration of parenteral nutrition and hospital stay.1 Abstract 4.1 Characteristics and outcomes Early Late Number (%) 189 (94) 183 (91) Gestation 31.2 31.1 Birth weight 1042 1018 Breast milk for fi rst feed (%) 82 88 Days to full feeds 18 (15–23) 21 (19–25)** Necrotising enterocolitis (number (%)) 25 (13) 20 (11) Sepsis (number (%)) 48 (25) 56 (31) Days of total parenteral nutrition (median (IQR)) 12 (9–15) 18 (13–18)** Died before discharge (total (%)) 11 (5) 10 (5) ** p<0.001. Results 404 babies were randomised – 202 in each group. Data are presented on 372 completed outcome sets to date. Conclusion Preterm infants with absent or reversed end-diastolic flow velocity on umbilical Doppler who were fed on Day 2 of life achieved full feeds earlier than those commenced on Day 6, with no difference in the incidence of NEC or sepsis.

Neonatal Respiratory Disorders

Of the numerous advances in neonatal medicine over the past 25 years, better understanding of neonatal lung disease has probably had the greatest impact on survival and quality of life. The development and use of therapeutic surfactant, the harnessing of microprocessor technology to neonatal ventilators, elucidation of developmental physiology and pathological mechanisms, as well as responses to treatment, have all helped to improve outcomes for newborn infants. The second edition of Greenough and Milner’s Neonatal Respiratory Disorders tells us where we stand today. The editors, two of the UK’s leaders in this area, have recruited a host of well-respected international contributors. The book is presented in four sections—development and physiology, antenatal and postnatal investigation, clinical management, and finally in section 4, eighteen chapters about specific pulmonary disorders. The coverage is certainly comprehensive, including both common and rare conditions affecting babies’ lungs as well as the effects on lung function of immaturity and of cardiac and neurological disease. Wider aspects of neonatal care which are important to lung function, such as fluid balance, circulatory support and nutrition, are also dealt with. So while this book focuses on the subject of the title, it does so in a very holistic manner. In terms of the depth of coverage for individual topics there are some surprises. In a book over 500 pages long only 56 pages are devoted to ‘respiratory support’. Given the scope of high-frequency oscillation, different modes of patient-triggered ventilation, volume guarantee, and the resurgence of interest in CPAP this initially seemed too little. However, despite its brevity the chapter proved to be a useful summary of the advantages and limitations of some of the older and newer techniques. It is also exceptionally well referenced (451 references), so the way to further information is clear. By contrast, chapters on control of breathing and measurement of lung function offer sufficient depth to form the basis of understanding for engaging in research. Surfactant has been one of the major developments in neonatal respiratory care, providing very effective prevention and treatment for respiratory distress syndrome. The first section of the book contains a whole chapter devoted to surfactant physiology; this is helpful since many aspects of function, particularly of surfactant proteins, are only now being recognized. In the section on clinical management, however, surfactant is hardly mentioned: one has to go to the chapters on individual conditions such as ‘respiratory distress syndrome’ to find a summary of meta-analyses of the therapeutic options, and to chapters on meconium aspiration and pulmonary haemorrhage for alternative uses. Corticosteroids were widely used for treatment of bronchopulmonary dysplasia for two decades but this strategy has been undermined by concern about the increased risk of cerebral palsy in treated infants. This topic, of great concern to neonatologists in recent years, gets hardly a mention. It must be emphasized, however, that the whole book is efficiently cross-referenced, and that all chapters make excellent and comprehensive reference to relevant publications. The clinical and physiological areas that are explored in greatest depth are those for which published summaries and systematic reviews are otherwise less easily available. So who is this book for? I would say that almost all those involved in neonatal care, from student to consultant, will find topics of interest. The day it arrived on my desk we were investigating a preterm infant with a mass in the thorax—suspected pulmonary sequestration. I decided to test the book, and there indeed were 4 pages devoted to the anatomy, pathophysiology and management of this rare condition. Apnoea, aspiration, airway problems, pulmonary hypoplasia, congenital abnormalities, pneumonia, air-leaks, pulmonary haemorrhage, pulmonary hypertension, broncho-pulmonary dysplasia—all are dealt with in a succinct yet detailed manner. This will be a welcome addition to any neonatal unit library, and in another ten years we shall be able to look back and say: well, that is how things were in 2003.