INFANT Copyright
BEHAVIOR AND DEVELOPMENT 0
1997
ABLEX Publishing
20 (4), 1997,
ISSN
pp. 553-557 All rights
Corporation
of reproduction
0163-6383
in any form
resewed.
BRIEF REPORT
The Effect of Mother-Infant Skin-to-Skin Contact on Plasma Cortisol and P-endorphin Concentrations in Preterm Newborns S. MOONCEY X. GIANNAKOULOPOULOS V. GLOVER Hammersmith
Hospital, London
D. ACOLET Hillingdon
Hospital,
Uxbridge
N. MODI Hammersmith
Hospital, London
The aim of this study was to assess the effect of mother-infant skin-to-skin contact on plasma pendorphin and cortisol concentrations in stable, preterm infants on a newborn intensive care unit. Blood samples were obtained before and at the end of a 20-min period of skin-to-skin contact. Similarly paired samples, obtained at the same times and after the same interval, without skin-toskin contact, were obtained on another day and served as controls. Both cortisol and P-endorphin concentrations fell significantly after the skin-to-skin session (cortisol: geometric mean change 66%. p = 0.008; P-endorphin: geometric mean change 74%, p = 0.002). There was also a signiticant fall in cortisol levels during the control session (geometric mean change 78%, p = 0.02), in contrast to P-endorphin levels, in which there was no significant change. Analysis of variance showed that the fall in P-endorphin, but not the fall in cortisol, during the skin-to-skin session was significant when compared with the control sesssion. These results emphasize the hormonal responsiveness of the preterm newborn to relatively minor interventions.We conclude that maternal skin-to-skin contact results in a significant reduction in circulating P-endorphin in the newborn; there was no evidence of any adverse effect. handling
P-endarphin
cartisol
There is continuing controversy concerning the role of handling for preterm newborns. Skin-toskin contact between mother and infant is a form of handling that has been advocated because it is thought to be both pleasurable and beneficial. Skin-to-skin contact has been found to decrease mortality (Bergmann & Jurisoo, 1994), lower the incidence of serious illness (Sloan, Camacho, Rojas, & Stem, 1994) and enhance maternal lactation (Whitelaw, Heisterkamp, Sleath, Acolet, & Richards, 1988). However, there has also been concern that extra handling of preterm infants may lead to harmful fluctuations in physiological parameters. As a consequence, many newborn intensive care units have “minimal
Direct all coprrespondence to N. Modi, MBChB MD FRCP, Department of Pediatrics & Neonatal Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
preterm
infant
stress
contact
handling” policies and discourage parents from touching their preterm infants (Harrison, Olivet, Cunningham, Bodin, & Hicks, 1996). Infants in newborn intensive care units are exposed to a number of stressful stimuli, often over a prolonged period. Preterm newborns and the human fetus, from at least 23 weeks gestation, mount hormonal stress responses to painful stimuli (Giannakoulopoulos, Sepulveda, Kourtis, Glover, & Fisk, 1994). Methods to alleviate stress are important both for the immediate care of the infant and for possible long-term benefits. Invasive procedures in the newborn period may influence future responses to pain, as suggested by a study which found that newborn circumcision affected responses to later vaccination in infancy (Taddio, Goldblach, Ipp, Stevens, & Koren, 1995). Studies in animals (Sapolsky, Uno, Rebert, & Finch, 1990) and humans 553
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Mooncey, Giannakoulopoulos,
(Starkman, Gebarski, Berent, & Schteingart, 1992) suggest that high levels of glucocorticoids are neurotoxic, especially to the hippocampal formation and that chronic hypercortisolaemia may have adverse effects on cognition and memory (Starkman et al., 1992). Pharmacological approaches have been used to attenuate the stress response in newborns receiving intensive care. In addition. various techniques aimed at providing a less stressful environment have been investigated. These include infant massage (Acolet et al., 1993) so-called “individualized” care (Als et al., 1994; Fleisher et al., 1995) and sound stimulation (Giannakoulopoulos, Murthy, Modi, & Glover, 1995). As part of a larger, prospective, investigation of the use of non-invasive, non-pharmacological techniques in the attenuation of stress responses, we aimed in this study, to determine the effect of maternal-infant skin-to-skin contact on plasma p-endorphin and cortisol concentrations in clinically stable, preterm newborns. Although pendorphin and cortisol often rise or fall together, they are also subject to independent control and we felt it would be of interest to measure them both. Our hypothesis was that both hormones would fall. METHODS Subjects Preterm infants cared for in the newborn intensive care units at Hammersmith Hospital and Queen Charlotte’s and Chelsea Hospital, who were clinically stable and breathing spontaneously, were eligible for this study which was approved by the Royal Postgraduate Medical School and Hammersmith Hospitals Trust Research Ethics Committee. Written consent was obtained from parents. Fifteen infants were studied. They were all stable at the time of this study but had all previously required full intensive care and continued to have high dependency monitoring. Three infants were still nursed in a closed incubator and 12 were in open cribs. Three infants were solely breastfed whilst the others were receiving a combination of nasogastric. breast and bottle feeds. Two infants were oxygen dependent and received it via nasal cannulae. Median gestational age at birth was 3 1 weeks (range 25-33) median postnatal age 21 days (range S-96), median birth weight 1420 g (range 520-1760) and median weight at the time of study 1583 g (range 1205-2313 g). Procedures The infants were studied between I I am and 3 pm on two days, a Monday and Thursday. This was to assure that one of each pair of blood samples coincided with clinical sampling. Room temperature was maintained between 24-28°C. All infants were fed by breast. bottle or nasogastric tube, at least
Modi, Acolet, and Glover half an hour prior to the commencement of the study. The longest feeding interval to study onset was 1 hour. No drugs were administered in the hour before the study period. The study took place in the “convalescent” nursery of the neonatal unit. This is a spacious room designed to containing 6 infants, with ample space for their parents to sit by them. It is lit by natural light and has a soothing and tranquil atmosphere. Murals are painted on the walls in pastel shades and there is little noise or activity. On the first study day the infant lay prone in his or her cot or incubator, tilted at an angle of 30-40 degrees. with no handling for an initial 40.nun period. The infants wore either gowns or all-in-ones. They were undressed by their mother and then held nude for a 20-min period of maternal skin-toskin contact between the mother’s bare breasts and covered by the mother’s blouse and a light blanket. The mother was seated on a standard rocking chair tilted at an angle of approximately 60”. On the second study day, which served as a control, the infant was left unhandled throughout the entire study period of 60 min. The infant remained fully clothed in a crib or incubator, lying prone at an angle of 30-40”. Heart rate and oxygen saturation were measured by the investigator (SM) using the Ohmeda Biox pulse oximeter after a 5-min stabilisation period. Recordings were made every 5 min during the first phase and every 2 min during the second phase. Axillary temperature was measured using a mercury thermometer prtor to and at completion of the study on both days. Blood samples (0.5 ml) were collected using a fine (27 FG) needle, from a vein on the dorsum of the hand. This is a standard and routine newborn procedure and causes minimal disturbance to the infant. They were obtained 5 to IO min prior to and after the total 60-nun study period on both days by the investigator (SM) who is an experienced neonatal medical practitioner. During the blood sampling the baby lay in his or her cot. There was no difficulty in obtaining the sample on any occasion. Samples were collected into heparinised tubes containing 1,000 KIU of trasylol per ml of blood and spun immediately at 600 g for 10 min. The plasma was then separated and stored at 70°C until assayed for cortisol and P-endorphin. Hormonal
Assays
Total plasma cortisol was determined using a commercially available radioimmunoassay (DPC Inc. California). B-Endorphin was determined in 100-300 pl of plasma using our previously described method, validated for use with small sample volumes (Giannakoulopoulos et al.. 1994). Statistical
Analysis
Values for cottisol and B-endorphin concentrations were not normally distributed, and were therefore transformed to their respective logarithms. These were then analyzed by Student’s paired t-test and by analysis of variance (ANOVA). Correlations were calculated using the Pearson’s correlation coefficient. Significance of comparisons and correlations was accepted at the two-sided 95% level, unless otherwise indicated.
Mother-infant
Skin-to-skin Contact
RESULTS All 15 infants remained stable throughout the study periods, without bradycardic nor apnoeic episodes. Oxygen flow requirements for the two oxygen dependent infants decreased during skin-to-skin contact by 25 cc/min. Body temperatures were maintained between 36.5 and 37°C. None of the infants cried during skin-to-skin contact, and all the mothers said they found the experience pleasurable. There were no significant changes in the physiological variables, heart rate, oxygen saturation, and body temperature, during either the control or skin-to-skin period. Changes in cortisol and P-endorphin concentrations during the skin-to-skin and control sessions are shown in Figure 1. Both cortisol and pendorphin concentrations fell significantly after the skin-to-skin session (cortisol: geometric mean change 66%, p = 0.008; P-endorphin: geometric mean change 74%,p = 0.002). There was also a significant fall in cortisol levels during the control session (geometric mean change 78%, p = 0.02), in contrast to P-endorphin levels, in
(conrrol) 800 $
which there was no significant change. Analysis of variance showed that the fall in P-endorphin during the skin-to-skin session was significant when compared with the control sesssion, but that there was no significant difference in the degree of fall of cortisol between the two sessions (P-endorphin: F( 1,14) = 5.70, p = 0.02; cortisol: F(1,14) = 0.04, p = 0.8). There was a wide variation in basal cortisol and P-endorphin levels on both days (control day: cortisol = 95-1560 nmolll, P-endorphin = lo-97 pg/ml; skin-to-skin day: cortisol = 47856 nmol/l, P-endorphin = lo-63 pg/ml). There were weak correlations between basal cortisol and B-endorphin values (control day: r = 0.37, p = 0.18; skin-to-skin day: r = 0.44, p = 0.1). DISCUSSION This study clearly shows that a brief period of maternal skin-to-skin contact after blood sampling brought about a reduction in circulating pendorphin. This response should be added to the list of previously reported effects of skin-to-skin contact (Bergman & Jurisoo, 1994; Sloan et al.,
(skin-lo-skin) .
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Figure 1. Plasma levels of cotiisol and P-endorphin before and after the control and skin-to-skin sessions. Values are for individual babies, with the horizontal bar marking the medlan.
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Mooncey, Giannakoulopoulos,
1994; Whitelaw et al., 1988). Although the role of p-endorphin in peripheral nociception is not yet clear, it has been shown to be secreted in response to stress in the fetus (Giannakoulopou10s et al., 1994) and in infants (Anand & Hickey, 1987). A reduction in peripheral p-endorphin levels presumably indicates that hypothalamopituitary-adrenal axis activity has been reduced. An unexpected finding in this study was the significant fall in cortisol level during the control session, unlike our previous studies of the effect of massage (Acolet et al., 1993), and intrauterine sound (Giannakoulopoulos et al., 1995) in which there was no significant change during the control period. This may be due to differences in design between the studies. In the intrauterine sound study (Giannakoulopoulos et al., 1995), blood samples were all taken from an indwelling line, and no stress would be expected to be associated with this. In the massage study (Acolet et al., 1993), the time schedule was different, with the second blood sample taken 2 hrs after the initial blood sampling. In the present study, the second blood sample was taken 65 to 70 mm after the initial sample. The fall in cortisol may represent a paradoxical response to the initial blood sampling. Lewis and Thomas (1990) found that 24 of 69 2-month old infants responded to the stress of an inoculation prick with a fall in salivary cortisol. The determinants and the longterm implications of this paradoxical response remain a matter for speculation, but these preliminary observations suggest a need for investigation. When designing future studies of this nature, it will be important to pay attention to the possible influence of potential confounds, including the method of blood collection and the time interval between baseline and subsequent samplings. These results emphasize the responsiveness of these hormonal systems in the newborn to relatively minor interventions. There is evidence that early experiences may have long-lasting effects. Ramsay and Lewis (1995) found differences in the cortisol response to inoculation at 2, 4, and 6. months between infants born at full term, in whom birth condition had been either optimal or non-optimal. Studies of rodents suggest that gentle handling in the newborn period attenuates hypothalamic-pituitary-adrenal axis responsiveness in the offspring for life (Meaney et al.. 1993). Nothing is as yet known about the
Modi, Acolet, and Glover
long-term effects of early mother-infant contact on future adrenocortical reactivity in the human. Further work is required to investigate both immediate and long-term effects of skin-to-skin contact on mothers and infants. We accept that this was a small study of a relatively heterogeneous group of babies with respect to both gestational and postnatal age. It would have been desirable to randomize the order of test and control days. These factors are potentially compromising, and the results therefore need to be confirmed in subsequent work. However, this study does provide some evidence that skin-to-skin contact attenuates pendorphin secretion in clinically stable, preterm newborns. The effect on circulating cortisol is less clear-cut. In addition, there was no adverse effect on any of the other physiological variables measured. As it was also regarded as a pleasurable experience by mothers, we suggest that nurses and clinicians should not be deterred from encouraging this practice. AUTHORS’
NOTES
We gratefully acknowledge the advice of Caroline Dare, Medical Statistics Unit, Hammersmith Hospital. REFERENCES Acolet, D., Modi, N., Giannakoulopoulos, X.. Bond, C., Weg, W., Glow, A.. & Clover, V. (1993). Changes in plasma cortisol and catecholamine concentrations in response to massage in preterm infants. Archives of Diseasr in Childhood, 68, 29-3 1. Als, H., Lawhon, G., Duffy, F. H., McAnulty. G. B., Gibes-Grossman, R., & Blickman, J.G. (1994). Individualized developmental care for the very low-birth-weight preterm infant. Journul offhr American Medical Association, 272. 853-858. Anand, K. J. S.. & Hickey. P. R. (1987). Pain and its effects on the human fetus and neonate. N~M England Jourml of Medicine. 317, 132 I - 1329. Bergman, N. J.. & Jurisoo, L. A. (1994). The “kangaroo-method” for treating low birth weight babies in a developing country. Tropical Doctor, 24, 57-60. Fleisher. B. E.. VandenBerg, K., Constaninou, J., Heiler, C., Benitz, W.E., Johnson, A.. Rosenthal, A., & Stevenson, D. K. (1995). Individualized developmental care for very low birth weight premature infants. Clinical Pediatrics, 34, 523-529.
Mother-infant
Skin-to-skin Contact
Giannakoulopoulos, X., Murthy, S., Modi, N., & Glover, V. (1995). Intrauterine-like sound stimulation is not associated with a change in circulating p-endorphin and cortisol in preterm infants. Journal of Reproductive and Infant Psychology,
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Giannakoulopoulos, X., Sepulveda, W., Kourtis, P., Glover, V., & Fisk, N. (1994). Fetal plasma cortisol and P-endorphin response to intrauterine needling. Lance& 344, 77. Harrison, L., Ohvet, L., Cunningham, K., Bodin, M. B., & Hicks, C. (1996). Effects of gentle human touch on preterm infants; pilot study results. Neonatal Network, 15, 35-42. Lewis, M., & Thomas, D. (1990). Cortisol release in infants in response to inoculation. Child Development, 61,50-59.
Meaney, M. J., Bhatnagar, S., Diorio, J., Larocque, S., Francis, D., O’Donnell, D., Shanks, N., Sharma, S., Smythe, J., & Viau, V. (1993). Molecular basis for the development of individual differences in the hypothalamic-pituitary adrenal stress response. Cellular and Molecular
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Sloan, N. L., Camacho, L. W., Rojas, E. P., & Stem, C. (1994). Kangaroo mother method: Randomised controlled trial of an alternative method of care for stabilised low birth weight infants. Lancet, 344, 782-785. Starkman, M. N., Gebarski, S. S., Berent, S., & Schteingart, D. E. (1992). Hippocampal formation volume, memory dysfunction and cortisol levels in patients with Gushing’s syndrome. Biological
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Taddio, A., Goldblach, M., Ipp, M., Stevens, B., & Koren, G. (1995). Effect of neonatal circumcision on pain responses during vaccination in boys. Lance& 345,291-292. Whitelaw, A., Heisterkamp, G., Sleath, K., Acolet, D., & Richards, M. (1988). Skin to skin contact for very low birthweight infants and their mothers. Archives of Disease in Childhood 63, 1377-1381.
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28 May 1996; Revised
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