John D Arnold

Pulmonary thromboemboli after neonatal asphyxia

Two surviving neonates with pulmonary thromboembolism, diagnosed by ventilation-perfusion lung scan, are described. Both infants had respiratory distress, and one had features consistent with persistent pulmonary hypertension of the neonate. These reports demonstrate that substantive pulmonary emboli can occur in neonates and may not be recognized without an appropriate level of clinical suspicion.

Effect of a cold stimulus on the synthesis of uncoupling protein in brown adipose tissue of rats and newborn rabbits.

Rats are known to respond to a cold stimulus by increasing the activity and amount of the uncoupling protein in brown adipose tissue. A 48 h cold stimulus was found to increase the synthesis of uncoupling protein 3.g-fold in 4–5 week old rats whereas no change was observed with newborn rabbits. The lack of response in the latter case may reflect a difference between rabbits and rats or that synthesis is already maximal in newborn rabbits.

EFFECT OF ANTENTAL STEROIDS ON PULSATILE SECRETION OF PLASMA CORTISOL IN PREMATURE NEONATES USING DECONVOLUTION ANALYSIS. † 1141

EFFECT OF ANTENTAL STEROIDS ON PULSATILE SECRETION OF PLASMA CORTISOL IN PREMATURE NEONATES USING DECONVOLUTION ANALYSIS. † 1141

Pharmacokinetics of Hydrocortisone in Extremely Premature Infants in the First Six Weeks of Life

Pharmacokinetics of Hydrocortisone in Extremely Premature Infants in the First Six Weeks of Life

Combined Therapy with Postnatal Corticosteroids and Indomethacin Increases the Risk of Surgery for Necrotising Enterocolitis (NEC)

Combined Therapy with Postnatal Corticosteroids and Indomethacin Increases the Risk of Surgery for Necrotising Enterocolitis (NEC)

Cortisol Production Rate is Related to Mean Arterial Blood Pressure in Neonates. |[dagger]| 811

There are few data on clinical factors that influence cortisol production rate (FPR) in neonates. This study aimed to provide such information. Blood samples for plasma cortisol (F) were taken via indwelling arterial lines at 15 min intervals for 6 hours in 42 clinically stable neonates (median ga 32 wks, range 25-41; median bw 1.95kg, range 0.64-3.88) studied in the first 9 postnatal days. None of the infants received vasopressor agents during the study and none received postnatal glucocorticoids prior to the study. We estimated FPR using deconvolution analysis. We prospectively collected data on antenatal steroid exposure, body surface area, gestational age, birth weight, the presence or absence of clinical interventions during the study, whether the neonate was intubated or extubated at time of study, mean arterial blood pressure (MABP), sex, SNAP score, and postnatal study day. MABP was recorded at 15 min intervals during the study and the values averaged to provide a single value for each neonate. The relationship between FPR and the above mentioned clinical factors was examined using univariate linear regression analysis (ULRA) and stepwise multiple linear regression analysis (SMLRA). Using ULRA, FPR correlated positively with postnatal study day (P = 0.0005, r= 0.51), MABP (P = 0.0006, r = 0.51) and being intubated (P = 0.011, r = 0.39). FPR did not significantly correlate with any other clinical factor. On SMLRA, these 3 clinical factors remained significantly correlated with FPR,(MABP, P = 0.0005; study day, P = 0.0085; intubated, P = 0.018). These 3 factors combined accounted for 51% of the variation in FPR (r2 = 0.51). We conclude that, assuming similar corticosteroid-binding globulin levels, FPR is related to MABP in neonates and to our knowledge this is the first time this relationship has been described. Our data support the concept that the low plasma F levels seen in association with hypotension in some premature neonates are consistent with cortisol insufficiency. We propose that this may be explained by decreased FPR in these neonates.

Effect of Blood Sampling Frequency on Characteristics of Plasma Cortisol Secretion in Neonates Using Deconvolution Analysis. 810

Studies in neonates, using blood sampling at 15 minute intervals, have demonstrated that cortisol (F) is secreted in discrete pulses approximately every 65 minutes. Deconvolution analysis is a mathematical technique which characterises pulses of hormone secretion over time in terms of two components; a pulse of secretion and a phase of elimination. The aim of this study was to determine the effect of less frequent blood sampling on deconvolution parameters for plasma F. Blood samples for plasma F were taken via indwelling arterial lines at 15 min intervals for 6 hours in 42 clinically stable neonates (median ga 32 wks, bw 1.95 kg) studied in the first 9 postnatal days. Characteristics of F secretion were estimated by deconvolution analysis for two groups of data; 15 min sampling (25 samples/6 hrs) and apparent 30 min sampling (12 samples/6 hrs). Pulsatile F secretion was observed in all infants. Data in the Table are given as median and inter-quartile range.

Effect of Gestational Age on Pulsatile Secretion of Plasma Cortisol in Neonates Using Deconvolution Analysis. † 809

Cortisol (F) is secreted in discrete pulses at approx 65 min intervals in neonates. The aim of this study was to assess the effect of gestational age on such pulsatile F secretion. Blood samples for plasma F were taken via indwelling arterial lines at 15 min intervals for 6 hours in neonates not exposed to antenatal steroids 36 wks (median ga 38 wks, bw 3.51 kg, n=9). Pulsatile F secretion was observed in all infants. Data in the Table are given as median and inter-quartile range.

EFFECT OF CLINICAL STATE AND CLINICAL INTERVENTIONS ON CHARACTERISTICS OF PLASMA CORTISOL SECRETION IN NEONATES USING DECONVOLUTION ANALYSIS. |[dagger]| 1142

“Non-stressed” NICU neonates have been shown to secrete cortisol (F) in discrete pulses at approx. 80 min intervals (Metzger JCEM 1993). Routine NICU clinical care often involves interventions and procedures. The aim of this study was to assess the effect of clinical state and interventions on plasma cortisol secretion in neonates. Blood samples for plasma F determination were taken via indwelling arterial lines at 15 min. intervals for six hours. Neonates with g.a. 25-40 wk were studied in the first 7 postnatal days. No infant had been exposed to antenatal steroid 5 (n = 10) had a greater amplitude of F secretion than those with a SNAP≤ 5 (n=11) [11.8 (5.8 - 22.5) vs 4.7 (3.5 - 10.2) nmol/L.min; P = 0.014] but did not differ with respect to other deconvolution parameters. Compared with extubated neonates (n=11) those who were intubated/ventilated (n = 10) had a greater mass of F secreted per burst and also a greater F production rate [214 (197 - 275) vs 108 (94 - 121) nmol/L; P = 0.003; and 981 (900 - 1100) vs 484 (299 - 756) nmol/L/6h; P = 0.002]. Clinical interventions, as part of necessary care, during the 6 hr study period included endotracheal reintubation, ET suction, intravenous insertion, nasogastric tube insertion and chest physiotherapy. The group with clinical interventions (n = 11) did not differ from those without interventions (n=10) for any deconvolution parameter. These data provide new information about the effect of clinical state and interventions on pulsatile cortisol secretion in neonates. The pulsatile nature of cortisol secretion must be taken into consideration when measuring plasma cortisol as a marker of stress, even in premature neonates.

MEASUREMENT OF THERMOGENIN SYNTHESIS IN BROWN ADIPOSE TISSUE (BAT)

Thermogenin is a mitochondrial inner membrane protein which mediates non-shivering thermogenesis in BAT. It has a molecular mass of 32,000 Da and acts by uncoupling mitochondria to produce heat. We report a method of measuring its synthesis. Polysomes were isolated from BAT of developing rabbits and translated in a reticulocyte protein synthesizing system. Newly synthesized thermogenin was isolated with monospecific antibodies. This technique has been applied in developing rabbits to demonstrate a 5-fold increase in thermogenin synthesis before birth, and a gradual decrease after birth.The technique provides a method to study other perinatal influences on thermogenin synthesis such as the effect of postnatal environmental temperature. In preliminary experiments thermogenin has been purified from human neonatal BAT.