No abstract

Preterm babies are exposed to multiple stressors and this may have long-term effects. In particular, high levels of endogenous cortisol might have a programming effect on the hypothalamicpituitary-adrenal axis as may administered glucocorticoids. In this study, we aimed to test the hypothesis that the level of endogenous and exogenous glucocorticoid exposure during the neonatal period predicts the saliva cortisol response to immunization at 4 mo of age. We followed 45 babies born below 32 wk gestation. We showed that their concentration of plasma cortisol during the first 4 wk was 358, 314, 231, and 195 nmol/L cortisol, respectively (geometric mean). This is four to seven times higher than fetal levels at the same gestational age range. We used routine immunization at 4 mo and 12 mo as a stressor and measured the change in saliva cortisol as the stress response. Mean circulating cortisol in the first 4 wk predicted the cortisol response at 4 but not at 12 mo. Path analysis showed that birthweight for gestational age, therapeutic antenatal steroids, and therapeutic postnatal steroids also contributed to the magnitude of the saliva cortisol response at 4 mo. There is considerable evidence from animal experiments that early exposure to stress, either in the antenatal or in the immediate postnatal periods, can have long term effects on both the function of the HPA axis, and on behavior (1-5). In general, the HPA axis of the offspring becomes hyperresponsive to a novel stressor. These effects are mediated, at least in part, by activation of the maternal HPA axis and the effect of fetal cortisol or corticosterone (in rodents) on the developing brain. These effects can, in some paradigms, be mimicked by synthetic glucocorticoids (6 -8). Until recently, this has been little studied in humans. It does appear that cortisol from the mother crosses the placenta in sufficient amounts to affect the fetus (9,10), although there is so far no direct evidence that maternal cortisol alters infant development. However, there is increasing evidence from epidemiologic studies that maternal stress and anxiety during pregnancy has an adverse effect on the development of the fetus and on the later behavior and cognitive development of the child (11-16).Preterm babies are exposed both to a stressful environment, with concomitant endogenous glucocorticoid release, and may also be exposed, antenatally and postnatally, to exogenous glucocorticoids used therapeutically. If the animal models are relevant, one would predict that these infants would show long-term effects, both in HPA axis response and in behavior. Babies born extremely preterm are at risk of later behavioral problems, most noticeably with attention deficit disorders (17). Recent evidence suggests that antenatal glucocorticoid exposure has long-term effects on brain development (18). Davis et al. (19) have shown preterm babies exposed to antenatal betamethasone had a lower saliva cortisol response to a heel stick than matched controls at 3-6 d after delivery. ABSTRACT1233 c...

No abstract

The agonists buprenorphine and L-␣-acetylmethadol (LAAM) were introduced as alternatives to methadone for treatment of the adult opiate addict. The direct and indirect effects of these drugs on normal fetal growth and development are currently under investigation in our laboratory. The goal of this report is to provide part of the data necessary to assess the safety of LAAM in treatment of the pregnant opiate addict. To achieve this goal, the technique of dual perfusion of placental lobule was utilized to determine the kinetics for transplacental transfer of LAAM and its effects on the viability and functional parameters of the tissue. LAAM is rapidly metabolized to the pharmacologically active norLAAM that was also included in this investigation. The two opiates were transfused at their plasma levels in patients under treatment, a concentration of 35 ng/ml.