J M Hawdon

Patterns of metabolic adaptation for preterm and term infants in the first neonatal week.

There have been few comprehensive accounts of the relationships between glucose and other metabolic fuels during the first postnatal week, especially in the context of modern feeding practises. A cross sectional study was performed of 156 term infants and 62 preterm infants to establish the normal ranges and interrelationships of blood glucose and intermediary metabolites in the first postnatal week, and to compare these with those of 52 older children. Blood glucose concentrations varied more for preterm than for term infants (1.5-12.2 mmol/l v 1.5-6.2 mmol/l), and preterm infants had low ketone body concentrations, even at low blood glucose concentrations. Breast feeding of term infants and enteral feeding of preterm infants appeared to enhance ketogenic ability. Term infants had lower prefeed blood glucose concentrations than children but, like children, appeared to be capable of producing ketone bodies. This study demonstrates that neonatal blood glucose concentrations should be considered in the context of availability of other metabolic fuels, and that the preterm infant has a limited ability to mobilise alternative fuels.

Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study

Background: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth. Methods: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling. Results: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes. Conclusion: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.

The Role of Mannose-Binding Lectin in Susceptibility to Infection in Preterm Neonates

Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the impact of MBL on susceptibility and severity of infection in preterm neonates during their first month of life. One hundred fifty eight preterm neonates were genotyped for MBL mutations by heteroduplex analyses. Consecutive serum MBL levels were measured by ELISA and clinical and laboratory data, including blood cultures, were collected for each baby. A third of the premature neonates had genetically determined MBL deficiency. In addition, MBL levels were also low in the first week of life and lower in neonates with a wild type genotype who were less than 28 wk gestation or a birth weight of less than 1000 g, thereby increasing the number of neonates with a low MBL level at birth. MBL deficiency was associated with an increased risk of sepsis (p < 0.01). This study indicates that MBL levels are low in neonates at birth and renders premature neonates to an increased risk of infection.

BORN TOO SMALL—IS OUTCOME STILL AFFECTED?

A cohort of boys weighing below the 2nd centile at birth between 1973 and 1974 were assessed at 10 to 11 years of age. Control children from the same population were matched for social class and age. Two boys in the light‐for‐dates group were profoundly disabled and were excluded from assessment. After these exclusions, there were no differences in intelligence or school achievement between the two groups, although tests of temperament and behaviour suggested some correlation between features of the ‘attention deficit disorder’ and the extent to which birthweight deviated from normal. Matching for social class is likely to have eliminated the confusing environmental and family influences associated with the poor outcome reported in a previous study of light‐for‐dates boys. In addition, improved perinatal care is likely to have contributed to the protection from long‐term sequelae of the light‐for‐dates infants in the present study.

Hypoglycaemia and the neonatal brain

Abstract There has been much controversy and confusion regarding potential damage caused to the neonatal brain by low blood glucose levels. Previous studies of outcome after neonatal hypoglycaemia are flawed by many factors including retrospective data collection and inability to control for co-existing clinical complications. There is no doubt that hypoglycaemic brain damage does occur but the severity and duration of low blood glucose levels required to cause lasting harm varies between subjects and is related to the ability of each baby to mount a protective response such as the production of ketone bodies which are alternative cerebral fuels. Evidence from studies of humans and other animals suggests that cortical damage and long-term sequelae occur after prolonged hypoglycaemia sufficiently severe to cause neurological signs. Conclusion Prolonged hypoglycaemia should be avoided by close clinical observation of vulnerable infants whilst avoiding excessively invasive management in populations of neonates which may jeopardise the successful establishment of breast feeding.

Optimal positions for the release of primitive neonatal reflexes stimulating breastfeeding

BACKGROUND Despite widespread skills-teaching, 37% of UK mothers initiating breastfeeding stop by six weeks suggesting a need to reappraise current support strategies. Rooting, sucking and swallowing have been studied extensively but little is known about the role other primitive neonatal reflexes (PNRs) might play to support breastfeeding. AIMS To describe and compare PNRs observed during feeding, investigating whether certain feeding behaviours and positions, collectively termed Biological Nurturing, (BN) are associated with the release of those reflexes pivotal in establishing successful feeding. METHOD 40 breastfed healthy term mother/baby pairs were recruited using quota sampling to stratify term gestational age. Feeding sessions were videotaped in the first postnatal month, either in hospital or at home. FINDINGS 20 PNRs were validated and classified into 4 types (endogenous, motor, rhythmic and anti-gravity) and 2 functional clusters (finding/latching, milk transfer) either stimulating or hindering feeding. Significantly more PNRs were observed as stimulants in semi-reclined postures (BN) than when mothers were upright or side-lying (p=<0.0005). DISCUSSION This study is the first to describe a range of semi-reclined maternal postures interacting with neonatal positions, releasing maternal instinctual behaviours and PNRs stimulating breastfeeding. Traditionally the human neonate has been considered a dorsal feeder with pressure needed along the babys back. Compelling visual data here illustrate that the newborn is an abdominal feeder and, like some other animals, displays anti-gravity reflexes aiding latch. Findings suggest that breastfeeding initiation is innate for both mother and baby, not learned, thus challenging the routine skills-teaching currently central to breastfeeding support.

Metabolic adaptation in small for gestational age infants.

Hypoglycaemia has long been recognised as a feature of the failure of metabolic adaptation in infants who are small for gestational age (SGA). This study examined the process of metabolic adaptation by measuring, longitudinally, the concentrations of metabolic fuels and substrates in 33 SGA infants in the first postnatal week, and relating these to cross sectional data in 218 infants of appropriate weight for gestational age (AGA). SGA term infants had higher mean blood lactate concentrations than AGA term infants at delivery (2.98 v 2.10 mmol/l) and in the first few postnatal hours (3.05 v 1.91 mmol/l). Subsequently, although there were no differences in blood glucose concentrations, SGA term infants had lower mean ketone body concentrations (for example day 2: 0.07 v 0.41 mmol/l), and failed to mount a ketogenic response to low blood glucose concentrations. At birth, SGA preterm infants had lower mean blood glucose concentrations than AGA preterm infants (3.17 v 4.16 mmol/l), but there were few postnatal metabolic differences between the two groups. Mean blood glucose concentrations did not differ between AGA and SGA preterm infants. For variables that differed between the groups, multiple regression analysis suggested that both the degree and asymmetry of growth retardation were related to the severity of the metabolic abnormalities. These data suggest that, although there are early metabolic differences between SGA and AGA infants, it is possible that current clinical management is effective in preventing subsequent hypoglycaemia. This is important because of the failure of SGA infants to mount a ketogenic response.

The role of pancreatic insulin secretion in neonatal glucoregulation. I. Healthy term and preterm infants.

The glucoregulatory role of insulin in adult subjects is undisputed. However, less is known about the secretion of insulin and its actions in the neonatal period, either for healthy subjects, or for those at risk of disordered blood glucose homoeostasis. The relationships between blood glucose and plasma immunoreactive insulin concentrations were therefore examined in 52 healthy children (aged 1 month-10 years), 67 appropriate birth weight for gestational age (AGA) term infants, and 39 AGA preterm neonates. In children and AGA neonates, plasma immunoreactive insulin concentration was positively related to blood glucose concentration. However, although both groups of neonates had significantly lower blood glucose concentrations than children, plasma immunoreactive insulin concentrations were significantly higher in both term and preterm neonates, when compared with children. The variation in plasma immunoreactive insulin concentrations was greater for neonates than for children. These data suggest, that compared with older subjects, plasma immunoreactive insulin concentrations are high in newborn babies and that neonatal pancreatic insulin secretion is less closely linked to circulating blood glucose concentrations. There are important implications for the interpretation of studies in hypoglycaemic and hyperglycaemic neonates.

Randomised, double-blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants

Background: Human milk has considerable short and long term benefits for preterm infants, but mothers may experience difficulties in expressing breast milk for infants too immature or sick to breast feed. Oxytocin has been used to assist breast feeding and milk expression, but few data are available to support this intervention in the neonatal unit setting. Aim: To test the hypothesis that oxytocin nasal spray increases early milk output in mothers expressing milk for preterm infants. Methods: A randomised, double blind trial of oxytocin nasal spray (100 µl per dose) versus placebo was conducted in mothers delivering infants <35 weeks gestation. Sprays were used before expression of milk using an electric pump up to day 5. Main outcome: Total weight of milk expressed while using spray (study powered to detect >1SD difference between groups). Secondary outcomes: Pattern of milk production; number of pumping sessions; weight/fat content of milk expressed during a fixed 20 minute period on day 5 (“physiological study”); mother’s opinion of expressing and spray assessed by questionnaire. Results: Fifty one mothers were randomised (27 oxytocin, 24 placebo). Total milk production did not differ between groups. Repeated measures analysis of variance suggested significantly (p  =  0.001) different patterns of milk production, with initial faster production in the oxytocin group then convergence between groups. Parity did not influence the response to the intervention. No significant differences were seen in milk weight or fat content in the physiological study nor in mothers’ opinions of milk expression and treatment. Conclusions: Despite marginal differences in the pattern of early milk production, the use of oxytocin nasal spray did not significantly improve outcome. Most mothers believed they were receiving the active spray, suggesting a significant placebo effect (supported by limited data from historical controls) and benefits from the extra breast feeding support available during the study.

Prevention and management of neonatal hypoglycaemia.

lines the evidence for a ketogenic response by term infants to blood glucose concentrations as low as <2-0 mmol/l. Therefore, it is not possible to claim that counter-regulation has failed if only blood glucose concentrations are measured. We feel that the presence of symptoms or the features of an underlying disorder are more important determinants of treatment than the blood glucose concentration alone, and would suggest that treating all asymptomatic term infants with blood glucose concentrations transiently below 2-0 mmol/l with intravenous glucose is over aggressive management. If clinicians are not comfortable with blood glucose concentrations as low as this, we suggest that the first line of treatment should be to increase enteral feed volumes and frequency with formula supplementation of breast feeds, and check postprandial increases in blood glucose concentration, rather than to separate mother and baby and commence invasive management. In fact, we do not agree that enteral feeds should be withheld from hypoglycaemic infants who have previously tolerated milk feeds, as there is no scientific support for Dr Mehtas speculation in section c (1) (iii) and he has not examined the effect of withholding enteral feeds on ketone body production. Rather, milk contains more energy/ml than 10% dextrose and its high fat content will provide substrate for ketogenesis. In addition, there is published evidence that enteral feeding may stimulate glucagon release and ketone body production.4 5 We agree that adequate intakes of intravenous glucose or enteral milk prevent hypoglycaemia in most preterm infants, but point out that there is a high prevalence of hypoglycaemia in preterm infants who are fluid restricted.5 In summary, we feel that it is inappropriate and potentially confusing to base the management of neonatal hypoglycaemia on hypotheses which are not fully scientifically tested. However, it should be noted that there is agreement between the two papers on the identification of groups at risk of failure of metabolic adaptation. J M HAWDON M P WARD PLATT A AYNSLEY-GREEN