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Background Instilling perfluorooctyl bromide (PFOB) into the fetal lung may lead to alveolar distension. Objective The aim of the study was to evaluate the safety of PFOB instillation into fetal lungs and to determine the radiographic distribution and tissue concentration of PFOB in New Zealand white rabbits. Methods Sibling fetuses of pregnant (day 27) New Zealand white rabbits were randomized to intratracheal instillation of 1 mL PFOB with tracheal ligation, instillation without ligation, and unmanipulated controls. The maternal animals were killed directly after instillation, at 3 or 6 hours (n = 10 each). For each study cohort, we determined fetal lung/body weight (FLBW) ratios, the radiographic distribution of PFOB, as well as pulmonary PFOB and water content by tissue distillation. PFOB concentrations in maternal and fetal tissues were assessed by gas chromatography. Results The relative amount of fetal lung PFOB recovered by fractional distillation was highest in ligated (25%) and lower in unligated lungs (9%). Extrapulmonary PFOB was found in the fetal brain (2.0 ± 0.7 ppm), but not in any other fetal or maternal tissues. Mean FLBW ratios were highest in ligated fetuses, followed by unligated fetuses and controls. PFOB partially displaced fetal lung water. PFOB was visible in the lungs of all treated fetuses. Fetal survival between manipulated and unmanipulated fetuses did not differ. Conclusions After prenatal intrapulmonary instillation, some PFOB remains in the lung, even if the trachea is not ligated, and may exert distending pressure on the alveoli.

We investigated whether premature infants nursed at the upper range of normal body temperature are more capable of maintaining their nasopharyngeal and rectal temperature when exposed to a 1 degrees C increase or a 1 degrees C decrease of incubator temperature. In a randomized controlled trial, premature infants were exposed to a 1 degrees C increase (T + 1 degrees C; n = 10), or to a 1 degrees C decrease (T - 1 degrees C; n = 10) of incubator temperature. Nasopharyngeal, rectal, and skin temperatures as well as heat flux at various sites, heart rate, and activity were measured over a 6-hour period. The absolute changes in core temperatures, Tnasoph and Trectal, were significantly greater in the T + 1 degrees C compared with T - 1 degrees C (T + 1 degrees C versus T - 1 degrees C: Tnasoph 0.44 +/- 0.31 degrees C and 0.18 +/- 0.14 degrees C respectively; p < 0.001; T(rectal) 0.43 +/- 0.30 degrees C and 0.25 +/- 0.10 degrees C, respectively; p < 0.01) when exposed to the increase or decrease in incubator temperature. Premature infants are less able to cope with increases in incubator temperature given that rectal and nasopharyngeal temperature change more when environmental temperature is increased.

To study the impact of lung water content and its reduction by a topically applied diuretic on respiratory and lung tissue mechanics in comparison with surfactant administration in surfactant-deficient newborn piglets with lavage-induced lung injury.Controlled, randomized study.Animal research facility.Newborn piglets. TREATMENT Piglets were surfactant depleted by lung lavage and, after a pretreatment period, randomly treated with intratracheal furosemide, furosemide and surfactant, or with surfactant alone.Dynamic compliance (C(DYN)), static compliance (C(ST)), stress-adaptation pressures (P(DIFF)) and post mortem lung water content were determined. Static compliance in the furosemide-surfactant group was not significantly higher than in the surfactant group. At the end of the study, C(ST) did not differ between the three groups because C(ST) in the furosemide group had increased to values similar to those of the surfactant-containing treatment groups: C(ST) F+S: 0.73 +/- 0.2 mL/cm H2O/kg body weight (BW); C(ST) S: 0.61 +/- 0.11 mL/cm H2O/kg BW; and C(ST) F: 0.60 +/- 0.19 mL/cm H2O/kg BW). Compliance was inversely and P(DIFF) was directly correlated to lung water (LW) content (C(ST) vs. LW: r2 = .59, p = .001; C(DYN) vs. LW: r2 = .49, p = .006; P(DIFF) vs. LW: r2 = .37, p = .059), independent of the type of treatment. Changes in C(ST) and C(DYN) were inversely related to changes in P(DIFF). Intrapulmonary furosemide was more rapidly absorbed when administered to the surfactant-depleted lung alone compared with the mixture with surfactant, and intrapulmonary furosemide had a rapid systemic effect.Although the combination of surfactant with a diuretic failed to increase respiratory compliance to a significantly larger extent than surfactant alone, furosemide at the end of the study increased respiratory compliance to a level similar to surfactant-containing treatments. Lung water content and, to a lesser extent, the absence or presence of surfactant appeared to determine lung mechanics, and its impact on lung mechanics was similar to surfactant administration.

OBJECTIVE: Mild hypothermia after perinatal hypoxic-ischemic encephalopathy (HIE) reduces neurologic sequelae without significant adverse effects, but studies are needed to determine the most-efficacious methods. METHODS: In the neo.nEURO.network trial, term neonates with clinical and electrophysiological evidence of HIE were assigned randomly to either a control group, with a rectal temperature of 37°C (range: 36.5–37.5°C), or a hypothermia group, cooled and maintained at a rectal temperature of 33.5°C (range: 33–34°C) with a cooling blanket for 72 hours, followed by slow rewarming. All infants received morphine (0.1 mg/kg) every 4 hours or an equivalent dose of fentanyl. Neurodevelopmental outcomes were assessed at the age of 18 to 21 months. The primary outcome was death or severe disability. RESULTS: A total of 129 newborn infants were enrolled, and 111 infants were evaluated at 18 to 21 months (53 in the hypothermia group and 58 in the normothermia group). The rates of death or severe disability were 51% in the hypothermia group and 83% in the normothermia group (P = .001; odds ratio: 0.21 [95% confidence interval [CI]: 0.09–0.54]; number needed to treat: 4 [95% CI: 3–9]). Hypothermia also had a statistically significant protective effect in the group with severe HIE (n = 77; P = .005; odds ratio: 0.17 [95% CI: 0.05–0.57]). Rates of adverse events during the intervention were similar in the 2 groups except for fewer clinical seizures in the hypothermia group. CONCLUSION: Systemic hypothermia in the neo.nEURO.network trial showed a strong neuroprotective effect and was effective in the severe HIE group.

Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n = 235) and one small RCT (n = 67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post resuscitation hypothermia in paediatric patients after cardiac arrest, but not after neonatal resuscitation. Subsequently, a whole body cooling trial supported by the NICHD reported a significant overall improvement in death or disability. Further large neonatal trials of hypothermia have stopped recruitment and their final results are likely to be published 2009–2011. Many important questions around the optimal therapeutic use of hypothermia remain to be answered. Nevertheless, independent meta-analyses of the published trials now indicate a consistent, robust beneficial effect of therapeutic hypothermia for moderate to severe neonatal encephalopathy, with a mean NNT between 6 and 8. Given that there is currently no other clinically proven treatment for infants with neonatal encephalopathy we propose that an interim advisory statement should be issued to support and guide the introduction of therapeutic hypothermia into routine clinical practice.

Background/Purpose Fetal tracheal occlusion (TO) accelerates lung growth but decreases surfactant production. We have previously shown that instillation of perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar to TO. This study compares neonatal lung mechanics and surfactant production after prenatal intrapulmonary PFOB instillation vs TO. Methods In each of 18 pregnant rabbits on gestational day 27, sets of 4 fetuses underwent either (1) intrapulmonary instillation of 1 mL PFOB, (2) TO, (3) instillation of 1 mL 0.9% NaCl (saline), and (4) hysteroamniotomy without fetal manipulation (control). Fetuses were born by cesarean delivery after 48 hours. Fetuses of 12 rabbits were mechanically ventilated for 15 minutes to evaluate lung compliance and airway resistance. Pulmonary surfactant protein B (SP-B) was quantified by immunohistochemistry in fetuses of the remaining 6 rabbits. Results Compliance was decreased in the TO group after cesarean delivery (0.33 ± 0.13 mL/cm H 2 O) compared with PFOB (0.59 ± 0.12 mL/cm H 2 O), saline (0.50 ± 0.12 mL/cm H 2 O), and control (0.52 ± 0.10 mL/cm H 2 O) fetuses. Mean fetal lung to body weight ratio was higher in TO and PFOB fetuses compared with saline and control. Higher water content and lower numbers of surfactant protein B–positive cells were found in the TO-treated fetuses. Conclusions Both prenatal intrapulmonary instillation of PFOB and TO accelerate lung growth, but TO is associated with decreased postnatal lung compliance, possibly influenced by decreased surfactant production and increased fluid retention. Conversely, instillation of PFOB preserved lung compliance and surfactant synthesis.

The study's aim was to evaluate whether prenatal instillation of perfluorooctylbromide (PFOB, a perfluorocarbon) into the lungs of fetal rabbits leads to increased lung growth. Hysteroamniotomy was performed in eight pregnant New Zealand white rabbits on gestational day 27. In each mother, four fetuses were randomized to undergo either 1) endotracheal intubation and intrapulmonary instillation of 1 ml PFOB, 2) intrapulmonary instillation of 1 ml 0.9% NaCl solution (saline), 3) no fetal manipulation (control), or 4) tracheal occlusion (TO). The distribution of PFOB was documented radiographically. The fetuses were born by cesarean section after 48 h, sacrificed, weighed, and their lungs excised. Fetal lung to body weight ratios (FLBW) were determined, and the lungs were snap frozen for histomorphologic analysis and lung tissue distillation. On macroscopic inspection, PFOB-filled and tracheally-occluded lungs were markedly larger than saline-filled and control lungs. Mean FLBW was higher in fetuses treated with intrapulmonary instillation of PFOB (0.037+/-0.009), compared with fetuses receiving saline (0.027+/-0.008) or the unmanipulated controls (0.028+/-0.008). FLBW was highest after TO (0.049+/-0.008). After 48 h, in-vivo radiographs did not demonstrate any residual PFOB. Average dry fetal left lung weight (in g) was much higher in the TO (0.064+/-0.029) and PFOB (0.062+/-0.016) fetuses compared with the saline (0.054+/-0.017) and control (0.043+/-0.012) groups. Alveolar architecture on microscopy was similar between all groups, although the alveolar septae appeared thicker and more cellular after PFOB treatment and TO. We concluded that prenatal intrapulmonary PFOB instillation leads to increased lung growth in the late gestation rabbit model. Although PFOB instillation resulted in lower wet FLBW than TO, the increase in dry lung weight is comparable. This novel technique may be a less invasive and less noxious treatment strategy for pulmonary hypoplasia associated with diaphragmatic hernia.

Bei der intrauterinen fetoskopischen Chirurgie ist eine Elektrokauterisation in der leitfahigen, elektrolytreichen Amnionflussigkeit nicht moglich. Da die Insufflation von Kohlendioxid in die Fruchtblase zu einer potentiell letalen Hyperkapnie und Azidose des Feten fuhrt (1), mussen andere intrauterine Medien fur die sichere, effektive intrauterine Chirurgie gefunden werden. Zielsetzung: In einem tierexperimentellen in-vitro Modell wurde die Einsatzfahigkeit und Effektivitat der bipolaren Elektrokauterisation in verschiedenen Medien miteinander verglichen. Methode: An insgesamt 14 frischen Haut-Knorpelpraparaten des Ohres von New Zealand White Kaninchen wurden unter standardisierten Bedingungen (Einwirkzeit, Gewebedruck, Intensitat) mit dem bipolaren Elektrokauter kontrollierte Gewebelasionen in 4 verschiedenen Umgebungsmedien gesetzt: 1) Luft, 2) Perfluordecalin, einem Perfluorcarbon (PFC), 3) Glycerinlosung und 4) Vollelektrolytlosung (Na+ 140; K+ 5; Ca++ 2,5; Mg++ 1,5; Cl− 153 mmol/l). Nach Fixierung und Hamalaun-Eosin-Farbung wurden Nekroseindices (NI, Quotient der nativen zur manipulierten Gewebedicke) der bearbeiteten Areale mikroskopisch ermittelt, die Gewebeveranderung qualitativ beschrieben und fur die verschiedenen Medien miteinander verglichen. Ergebnisse: In den bearbeiteten Arealen zeigten sich deutliche histologische Veranderungen wie die Ausdunnung des Gewebes, eine Aufhebung der Architektur mit verstarkter Anfarbung des Stromas, sowie Zeichen der Kariorhexis. Fur die Elektrokauterisation ergab sich kein signifikanter Unterschied der NI bei Glycerin (1,39 ± 0,34; p= 0,35) und PFC (1,37 ± 0,20; p = 0,39) im Vergleich zu Luft (1,35 ± 0,22). Kein wesentlicher Kauterisierungseffekt ergab sich in der Elektrolytlosung (NI = 1,05 ± 0,13; p < 0,001). Schluβfolgerung und Ausblick: Unter den flussigen Medien bieten PFC und Glycerin gleich gute Voraussetzungen fur eine effektive Elektrokauterisation. Die Vorteile fur den Einsatz von PFC bei der intrauterinen fetoskopischen Chirurgie sind die Grenzflachenbildung zu Blut und die inerten biologischen Eigenschaften der Substanz. Im Vergleich zum hyperosmolaren Glycerin ist PFC nicht osmotisch wirksam. Die Durchfuhrbarkeit des Fruchtwasserersatzes mit PFC wurde von uns im Tierexperiment bereits bestatigt.

Objectives: (a) To investigate in a newborn animal model whether nasopharyngeal temperature is more closely related to epidural brain temperature than rectal temperature and (b) to investigate in human neonates whether measurement of nasopharyngeal temperature is dependent on the measurement site and other conditions. Design and setting: (a) Animal experiment in newborn piglets, at an institute for surgical research. (b) Prospective study in human neonates, at a neonatal intensive care unit of a tertiary care university hospital. Animals and patients: (a) Nineteen tracheostomized ventilated newborn piglets. (b) Twenty-two spontaneously breathing human newborns nursed either in an incubator or a cot. Measurements and results: (a) In the piglets nasopharyngeal temperature (Tnasoph) measured at the nose-ear distance, defined as distance from the inner brim of the nostril to the tragus and inner rim of the meatus accusticus, most closely reflected epidural temperature (Tepidur) at the epidural surface (r 2=0.89), followed by skin temperature at the temple, rectal temperature (Trectum) at 2 cm depth, and esophageal temperature (Tesoph) in the middle esophagus. Tnasoph did not significantly differ before and after tracheostomy. (b) In the newborns Tnasoph was significantly lower than Trectum. Measurements of Tnasoph at nose-ear distance within a feeding tube had a high precision and were unaffected by breathing or head turning. A nasopharyngeal probe was imaged by magnetic resonance imaging in four newborns of various body weight; its tip when inserted to a depth equal to nose-ear distance was anatomically closest to the brain base but separated from it by tissue layer 2.2 cm thick. Conclusions: Tnasoph measured at a position anatomically closest to the brain reflects epidural brain temperature more closely than Trectum. When measured at nose-ear distance it is unaffected by breathing or head turning. Measuring Tnasoph within a feeding tube and standardizing the measuring position is crucial for its use as brain temperature analogue.

To the Editor.— It has always been challenging to know when new therapies should be considered ready for use in practice. History has provided many contrasting examples of simple and effective treatments (such as phototherapy and antenatal steroids) that languished for decades before being adopted and treatments that were and often continue to be used well after they proved to be either useless or less effective than simpler alternatives. However, it is extremely difficult to understand why Kirpalani and colleagues1 are so concerned that some neonatologists are now choosing to offer therapeutic hypothermia on a compassionate basis. Neither these practitioners nor any official body have, to our knowledge, declared that hypothermia should be the standard of care. They, and several of the undersigned, helped develop the consensus of the 2005 National Institute of Child Health and Human Development workshop that hypothermia is an evolving (not unproven or experimental) therapy, with many questions around its optimal use.2 Thus, the underlying premise of their commentary is shaky. Three independent …

Summary Background Neonatal sepsis is a common and lifethreatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis. Methods In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days −4 to −1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day −4. Findings 101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day −1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%. Interpretation IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.

Body temperature is one of the most traditionally and generally used terms in medicine and biology but without a precise working definition or thorough physiologic understanding (See below: Definitions). The reasons why body temperatures are measured are rarely considered and consequently it is difficult to choose from the many temperatures and the methods used to measure them (See below: Aims). These methods of temperature measurement have been described in detail and their accuracy and precision characterized but special problems arising in the newborn e.g in measuring esophageal or deep head temperature, have not been addressed (See below: Methods). There is no clear synopsis of temperatures synchronously measured in newborns and in particular in the sick infant who represents a different challenge in terms of measurement of tissue temperature (See below: Profiles in health and disease). Finally, there are no recommendations about which temperature or temperature set, from the many available, should be measured in which patient (See below: Recommendations). This article attempts to answer some of these questions.

The shape of the volume-pressure (V/P) curve indicates alveolar collapse if it is convex to the pressure axis and indicates overdistension if it is concave. Positive end-expiratory pressure (PEEP) should either improve or decrease compliance and oxygenation in neonates ventilated for respiratory distress syndrome (RDS), depending on predominance of either alveolar collapse or overdistension. To test this hypothesis, we determined quasistatic V/P curves in 13 preterm neonates and characterized their shape by an alveolar distension index (ADI) at PEEP levels of 2, 4, and 6 cm H 2 O. We calculated the ADI dividing the V/P ratio at a low tidal volume by the V/P ratio at a high tidal volume. This ADI was then related to the effect of PEEP changes on respiratory compliance and alveolar to arterial oxygen tension difference (AaDO 2 ). ADI was assumed to indicate alveolar collapse if less than 1 and overdistension if more than 1. An increased PEEP in neonates with alveolar collapse (ADI less than 1) decreased AaDO 2 more (12 vs 10 mm Hg/cm PEEP, not significant) and decreased compliance less (3 vs 17%/cm PEEP; P

Background: 2 treatment strategies to compare GE and LM in artificial RDS after lavage (paO2 constantly < 13 kPa; lung compliance(Crs< ½ baseline, FiO2=1.0 and VT=5-10 ml/kg). Subjects: 13 newborn piglets (< 2 days: MW. 1708 g). Measurement of Crs. blood gases, systemic and pressure of respiratory system before (baseline), 0 and 60 min after injury and 15, 30, 60 and 120 min. after intervention: Randomized surfactant (n=7: Alveofact 100 mg/kg) or RM 101 (n=6; 2 ml/kg/min initially, reduced to 0.5 ml/kg/min) intratracheal via bypass-tube without disconnecting ventilation.

Eighteen diabetic children aged between 8.5 and 16.5 years (mean 12.5 years) who had been diabetic for 1 to 10 years (mean 4.1 years) were examined for their urinary glomerular basement membrane (GBM) antigen excretion by means of immunoelectrophoresis and for alterations of the retinal vessels by fluorescence angiography. None of these patients showed albuminuria or hypertension. As compared to 40 healthy controls aged between 5 and 17 years, altered GBM antigen mobility (alpha-1) was found in 9 out of these 18 diabetics, whereas the remaining 9 children had normal GBM antigen mobility (alpha-2). Pathological fluorescence angiography findings on the other hand were evident in 7 children with altered GBM mobility, but only in 4 diabetics with normal GBM antigen mobility. This trend reflects the similarity of biochemical and functional characteristics of basement membranes in the retinal and kidney vessels supporting the well established association of vascular changes in both organs in patients with diabetes mellitus. GBM antigen excretion into urine could be useful for detecting early microvascular alterations in the kidneys in juvenile diabetics where diagnosis of early glomerulosclerosis is important.

A modified method for registering non-nutritive sucking behaviour with and without taste stimulation enabled us to study taste perception of premature babies. We wanted to study how babies who had no extrauterine taste experience reacted to one or more stimuli with water and 33% glucose. Eight randomly selected healthy newborns (three of them being SGA without further symptoms), exclusively fed by gastric tube, were studied. The mean gestational age at the time of the study was 35.5 weeks. They were studied five times with water and five times with glucose just before feeding. In seven babies the sucking response to glucose was greater than that to water from the first trial onwards. Sucking response increased with repeated glucose stimulation, but remained the same with water stimulation. The eighth baby behaved completely differently. We concluded from our results that premature babies with a postconceptional age of 35 weeks can discriminate between sweet and not-sweet. The greater sucking response to glucose than to water at the first trial implies a genetic factor in the preference for sweet in humans.

A method for directly assessing the metabolic rate of the fetus for optimal management of labor and delivery is still being studied. Since heat, an end product of metabolism, is dissipated from the fetal surface, we measured the heat flux from the fetal scalp and related it to the pH of fetal scalp blood, a measure of metabolism. In 25 human fetuses at risk of intrapartum hypoxia, after the membranes had ruptured and the cervix dilated to greater than 3 cm, we attached a heat flux transducer, a platelet of 2.5 cm diameter and 1 mm thickness, to the fetal scalp and recorded continuously the heat flux from then until delivery. We also obtained one sample of fetal scalp blood in all patients and two such samples in 13 patients for the analysis of pH. We found a significant correlation between heat flux measured immediately before the scalp blood sampling (presampling values) and the pH of fetal scalp blood (r = 0.736; n = 18 presampling values; p less than 0.001). Out of 13 fetuses with two scalp blood samples, the changes in the scalp heat flux paralleled changes in scalp blood pH in 11. We conclude that fetal scalp heat flux is related to the metabolic condition of the fetus. Measuring scalp heat flux during labor could be developed into a noninvasive method for a continuous and more direct assessment of the fetal metabolic rate.

68 CALORIMETRIC BIKINIS FOR THE UNHINDERED, LONGTERM ASSESSMENT OF DRY HEAT LOSS IN NEWBORN INFANTS

Top of pageAbstract Enzyme replacement therapy for a severely affected premature boy (birthweight: 2380 g, GA:36 weeks) with hypophosphatasia was attempted by infusions of purified human hepatic alkaline phosphatase(AP). Treatment started at age of two weeks and was repeated in weekly intervals until death (10 weeks). Samples of AP were diluted with 10 ml of physiological saline and infused over a time span of 30 minutes via an umbilical arterial catheter. No toxic or allergic side effects were observed. Serum-AP increased from 3 mU/ml before treatment to a maximum level of 195 mU/ml with a half-life time between 37 and 62 hours. Urinary excretion of phosphoethanolamine (PEA) decreased under therapy from a maximal value of 9.5 to 5.5 μmol/mg creatinine (normal: < 0.4). Calcium, phosphorus, parathormone and 1-25 dihydroxyvitamin D levels were within the normal range during therapy. Sequential radiographic studies showed no improvement of bone mineralization under therapy. Bone morphology was studied by light and electron microscopy before treatment and post mortem. In contrast to previous studies an unusually woven bundle bone structure was found with abrupt mineralization fronts without osteoblast-like cells. We conclude that this enzyme, substituted for the first time, altered PEA concentrations but failed to influence the iniiial abnormal bone structure of this infant.