A novel infant formula milk with added long-chain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and health.

OBJECTIVE: To evaluate the growth, feeding and health of babies fed a novel infant formula milk with added long chain polyunsaturated fatty acids (LCPs) produced from single-cell sources, at concentrations similar to those found in mature breast milk. DESIGN: Randomized double-blind control trial. SUBJECTS: One-hundred and forty healthy, full-term infants of birth weight 2.5-4.5 kg born at the Maternity Department, East Glamorgan General Hospital, Wales, whose mothers had already decided to bottle feed. INTERVENTIONS: Subjects were randomized to two groups; one (control group) to receive a standard formula milk and the other to receive the trial milk with added LCPs. Milks were supplied in a double-blind fashion and given for the first 12 weeks of life. Anthropometric measurements were made at recruitment, 3 months, 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months, and a parental record was kept of any ill health suffered by the subjects during the first year of life. RESULTS: Of 140 infants recruited, 31 did not complete the protocol. Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months, that in the trial group being slightly higher, but unlikely to be of any clinical importance. No differences were found in the feeding patterns of the infants in the two groups. Stool patterns were similar, as were the frequencies of illness and allergy. CONCLUSIONS: This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth, feeding and general health of infants.

Confidential enquiry into deaths due to prematurity.

The aim of this study was to audit the management of neonatal respiratory distress syndrome (RDS) in a geographically defined population using a retrospective peer review of case notes. The subjects were 49 infants of 24-36 wk gestation with a birthweight >499 g, and dying as a consequence of prematurity at <1 y of age in Wales during 1996. Forty-four infants (90%) were delivered in a unit with staff experienced in the management of preterm birth. Of the 30 infants <30 weeks' gestation, 29 (97%) received neonatal intensive care on a (sub)regional unit. Predelivery corticosteroids were indicated in 34 cases and administered in 31 (91%). Resuscitation at birth was indicated in 47 infants and conducted satisfactorily in 42 (89%). Temperature on admission to the neonatal unit was not recorded in 7 infants; in the other 42 it was >35.5 degrees C in 21 (50%). Early surfactant therapy was administered to 31/34 (91%) infants still intubated 120 min after birth, but was given within 30 min to only 8 (24%). Mechanical ventilation was assessed in 41 infants and considered to be good in 23 (56%). Cardiovascular therapy was evaluated in 40 infants requiring active support and considered to be good in 31 (78%). We concluded that neonatal RDS was generally well managed, thermal care during resuscitation was poor, surfactant should be administered more promptly, and deficiencies in the management of ventilation were common and related mainly to poor anticipation and a slow response to problems.

Effect of patency of the ductus arteriosus on blood pressure in very preterm infants.

Forty one preterm infants (birth weight < 1500 g) were studied by daily Doppler echocardiography for the first week of life to examine the effect of a haemodynamically significant ductus arteriosus (HSDA) on systemic blood pressure. Hourly records of blood pressure were averaged for each infant to produce a 24 hour mean value and the infants were then allocated to groups according to whether, by echocardiographic criteria, there was a HSDA on that day. In infants from 1000 to 1500 g the differences in all parameters of blood pressure between those with and without a HSDA were not significant. In infants < 1000 g the mean blood pressure was significantly less in the infants with a HSDA throughout the first week of life. Systolic blood pressure was reduced by as much as diastolic blood pressure and as a result the pulse pressure did not differ. Infants < 1000 g with a HSDA were given more plasma and a greater number received inotropic support. Gestational age, respiratory disease severity, and complication rates did not differ between those with and without a HSDA. The possibility of a clinically silent HSDA should be considered before large amounts of plasma volume expanders are given to treat hypotension in infants < 1000 g.

Global and depth resolved phosphorus magnetic resonance spectroscopy to predict outcome after birth asphyxia.

Twelve normal and 32 asphyxiated neonates were studied using global and depth resolved phosphorus magnetic resonance spectroscopy (31PMRS). Eight of the asphyxiated group died or survived with major neurodevelopmental abnormalities. A global phosphocreatinine/inorganic phosphate (PCr/Pi) ratio below the range of values from normal infants predicted adverse outcome after asphyxia with a positive predictive value of 64%, sensitivity 88%, and specificity 83%. Corresponding values for global inorganic orthophosphate/adenosine triphosphate (Pi/ATP) ratios were positive predictive value 88%, sensitivity 96%, and specificity 88%. Spatially localised MRS data, obtained using phase modulated rotating frame imaging, showed cerebral energy metabolism to be more abnormal in deep than superficial regions after birth asphyxia. However, in this population of full term infants none of the regional metabolite concentrations were superior to global data for prediction of outcome.

Magnetic resonance spectroscopy.

MRS is a noninvasive technique that does not use ionizing radiation and can be used to measure relative metabolite concentrations in human tissues and organs in vivo. Phosphorus MRS can be used to study energy metabolites and intracellular pH. The first neonatal applications were described in 1983 in a study of cerebral metabolism. Since then, the value of cerebral MRS as research tool and an investigative technique has been confirmed, and its prognostic power in asphyxiated infants has been established. Techniques of spatial localization and quantitation have been developed, but studies of other organs and the use of other nuclei remain at a very preliminary stage. Considering the huge potential of MRS and the proliferation of high field magnets primarily designed for imaging, there has been a disappointing lack of progress in the development of clinical and research applications of spectroscopy. The logistic differences of studying sick infants in strong magnetic fields make MRS a time-consuming and labor-intensive investigation, which will inevitably limit its widespread routine use. Research studies are hampered by the diversity of spectroscopic and signal processing techniques, which make comparisons of data from different groups impossible. Some techniques for the assessment of cerebral hemodynamics such as doppler ultrasound and near infrared spectroscopy have the advantage of being available at the cotside, but MRS is unique in providing quantitative information about a wide range of intracellular metabolites. The altricial development of MRS as a clinical investigative tool in neonatology can be ascribed partly to practical difficulties, but these should not detract from the exciting possibilities opened up by a technique that gives a noninvasive insight into intracellular chemistry. The metabolic information from MRS is an invaluable addition to the information provided by other techniques and will certainly play an important role in unraveling the sequence of events between an hypoxic-ischemic insult and cell death. A better understanding of these mechanisms is a prerequisite to the development of rational therapeutic maneuvers following asphyxial insults.

Spatially localized magnetic resonance spectroscopy of the brains of normal and asphyxiated newborns.

Phase-modulated rotating frame imaging is a modification of magnetic resonance spectroscopy, which uses a linear radiofrequency field gradient to obtain spatially localized biochemical information. Phase-modulated rotating frame imaging was used to study regional cerebral energy metabolism in the brains of 9 normal newborns and 25 newborns after birth asphyxia. Relative concentrations of phosphorus-containing metabolites and intracellular pH were determined for brain tissue at three specified depths below the brain surface for all neonates. Wide variations in metabolite ratios were seen among normal neonates, and considerable metabolic heterogeneity was demonstrated in individual neonates by depth-resolved spectroscopy. Asphyxiated neonates with severe hypoxic-ischemic encephalopathy and a poor neurodevelopmental outcome showed the expected rise in inorganic orthophosphate and fall in phosphocreatine concentrations in both global and spatially localized spectra. Phase-modulated rotating frame imaging showed that metabolic derangement was less in superficial than in deeper brain tissue. The inorganic orthophosphate-adenosine triphosphate ratio from 1 to 2 cm below the brain surface was more accurate than any global metabolite ratio for the identification of neonates with a poor short-term outcome. These data are consistent with the known vulnerability of subcortical brain tissue to hypoxic-ischemic injury in the full-term neonate.

Birth asphyxia and the intrapartum cardiotocograph.

The intrapartum cardiotocographs (CTGs) of 38 severely asphyxiated, term infants, born during a 17-month period, and those of 120 healthy term infants acting as controls were independently reviewed by three investigators who were unaware of the clinical outcome. Inter-observer agreement was good (Kappa statistic = 0.74, P less than 0.0001). The investigators found that cardiotocographic abnormalities were present in 33 of the asphyxiated infants (87%) and in 35 of the controls (29%) and predicted that the abnormalities were severe enough to lead to significant fetal metabolic acidosis at delivery in 23 asphyxiated infants (61%) and in 11 controls (9%). The differences between the two groups were highly significant (P less than 0.001). Using the traditional diagnostic criteria for fetal distress, the investigators found that fetal blood sampling was indicated in 58% of cases in the asphyxia group and in 20% of controls but was only performed in 16% of asphyxiated infants and in 8% of controls. Furthermore, the median response times of delivery suite staff for abnormal fetal heart rate patterns were similar whether the FHR changes, classified using Krebs' CTG scoring system, were moderate or severe: 80 min and 90 min, respectively. These findings suggest that interpretation of the intrapartum CTG continues to pose major problems for practising obstetricians.

The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy.

Mazindol has been reported to improve muscle function in Duchenne muscular dystrophy (DMD) by virtue of its growth hormone (GH) suppression. The effects were studied on GH secretion (in response to growth hormone releasing factor and sleep) of mazindol 2 mg daily for 3 months in five boys with DMD. No consistent change was found following mazindol therapy. Adverse effects were noted in all the boys which may preclude long term use of mazindol in DMD.

Changes in the mucosa of colon conduits with particular reference to the risk of malignant change.

Intestinal suction biopsies were obtained in 15 infants and children with cutaneous colo-ureterostomies. The patients were subdivided into groups according to the length of time the conduit had been established, i.e. less than 5 years, 5 to 10 years, 10 to 15 years and over 15 years. The histological changes found were chronic inflammation with a dense infiltration of plasma cells and eosinophils. The changes were progressive and correlated with the length of time the conduit had been established. As persistent chronic inflammation is a precursor of malignancy, it seems likely that there is a risk of malignant change in these conduits. Regular follow-up of such patients is recommended and should include flexible fibreoptic endoscopy of the conduit.