The flexion reflex threshold has been used as a measure of sensation in a group of premature infants born at 27-32 weeks postmenstrual age. The threshold in an area of local tissue damage created by routine heel lances was half the threshold on the intact heel on the other side. This indicated a hypersensitivity to tissue damage analogous to tenderness or hyperalgesia reported in adults. In a double-blind study, treatment of the damaged area with the topical anaesthetic cream, EMLA, was found to reverse this hypersensitivity or in other words increase the flexion reflex threshold. Treatment with placebo had no effect. The results show that the newborn infant central nervous system is capable of mounting a chronic pain response to local injury which can be reduced by local anaesthetic.

Background: Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo. Objectives: To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis. Methods: Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks' gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before , during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia. Results: No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio 2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (PϽ.001) and midazolam (P = .002) infusions compared with the placebo group. Conclusions: This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pil...

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Aim-To determine ranges for skin temperatures in infants weighing under 1000 g in the first five days of life. Method-Abdominal skin and foot temperatures were automatically collected each second, averaged over 1 minute and stored on computer. A computer program analysed the data in 83 babies weighing under 1000 g at birth over the first five days of life and expressed the temperatures as means and standard deviation. The temperature patterns seen in these babies were also visually analysed. The relation between an increasing abdominal skin-foot temperature diVerence and other signs of hypovolaemia was also studied. Results-These