Long-term effects of routine morphine infusion in newborns who received ventilatory support

Worldwide, many newborns are admitted to the neonatal intensive care unit
(NICU) because of prematurity, perinatal problems, congenital anomalies or
severe illness. Even fairly recently, newborns on the NICU experience on
average 14 painful procedures per day and more than 65% of these children does
not receive appropriate analgesic therapy [1] . As several studies have
indicated that neonatal pain experience might negatively affect long-term
outcome [2-4], adequate analgesic therapy during neonatal intensive care is
warranted (NIH/ FDA meeting April 2004).
Recently, our group showed that neonatal pain exposure results in long-term
alterations in somatosensory functioning, namely hyposensitivity to the
detection of temperature and hypersensitivity for pain even up to the age of 8.
We also found that high dosages of morphine in children treated with ECMO
resulted in generalized hyposensitivity for temperature detection. It is
possible that the amount of morphine played a role in the development of this
hyposensitivity (Schouw submitted).
Neonatal pain experiences not only has effects on the somatosensory
functioning, but also on the functioning of the hypothalamic-pituitary-adrenal
axis (HPA-axis) [5]. It seems that pain influences stress reactions in
neonates, but also has been suggested to change stress responses at older ages
[6, 7]. Whether this can be prevented by the use of judicious morphine during
the neonatal period is unknown.

To evaluate detection thresholds, functioning of the HPA-axis and risk of
chronic pain in children of 5-years of age who experienced pain and received
morphine in neonatal period in compare with children of 5-years of age who
experienced pain without morphine.

Experimental study. All children participated in this larger neonatal
randomized, double-blind, placebo-controlled trial (n=150) in the Erasmus
MC-Sophia Rotterdam and Isala Clinics Zwolle in the period 2000-2003
(MW-NWO-940-31-048).
All children who participated in this study will already been seen within the
standard follow up for premature infants at the age of 5.3 years. As an
addition this standard procedure for follow up, we will assess the detection
threshold for a warm or cold stimuli and stress response.

Subjects aren*t in any risk by participating in this research. The importance
of this research is to know more about the long-term effects of pain and
morphine, while in future ventilated children can be better taken cared for.
Previous research (P02.616C) showed that children liked to cooperate with the
detection of warmt and cold, because the children control the device by
themselves. Thermal limitations prevent risks of tissue dammage and pain.