www.AJOG.org BASIC SCIENCE: OBSTETRICS Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery Christine Schuller, MD; Nina Känel, MD; Olivia Müller, MD; André Boris Kind, MD; Eva Maria Tinner, MD; Irene Hösli, MD; Roland Zimmermann, MD; Daniel Surbek, MD OBJECTIVE: The objective of the study was to compare the stress re- RESULTS: Significant differences were evident during the first 72 hours
sponse and pain expression of newborns (NBs) in the early postpartum
postpartum with highest nominations in the VE group. Meconium-
stained amniotic fluid was the only intrapartum stress factor with an im-
STUDY DESIGN: This was a prospective study with 280 NBs enclosed at 3
Swiss university hospitals. Stress response and pain reaction were analyzed
CONCLUSION: NBs delivered vaginally show a higher incidence of
according to the mode of delivery: elective cesarean section (ELCS), spon-
stress response and pain expression than infants of the ELCS group.
taneous vaginal delivery, and assisted vaginal delivery by vacuum extraction
The long-term impact of these findings remains to be determined.
(VE). Saliva cortisol and clinical pain expression were evaluated after deliv-ery and before and after heel prick for metabolic screening.
Key words: newborn, pain assessment, postpartum stress response
Cite this article as: Schuller C, Känel N, Müller O, et al. Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery. Am J Obstet Gynecol 2012;207:xx-xx. Afewdecadesago,itwasscientificbe- opedinthefetusat20-24weeksofges- Childbirth is considered to be the
capability to perceive pain at all or only
tivity of a newborn‘s brain can be found
riod. Previous literature describes a dif-
ies, the mode of delivery results in spe-
nerve tracts and neurons are fully devel-
fluids (umbilical cord blood, saliva). The
validated pain scores specially developed
are linked to relevant clinical pain in the
Switzerland (Drs Schuller, Känel, Müller, Kind,
and Surbek); Department of Obstetrics and
Pain Scale, Échelle de Douleur Inconfort
Switzerland (Drs Hösli, Kind, and Tinner); and
infants born by assisted vaginal delivery
University Hospital Zürich, Switzerland (Dr
Received May 24, 2012; revised July 24, 2012;
levels and the expression of relevant pain,
Freiwillige Akademische Gesellschaft Basel,
we investigated newborns’ clinical pain as-
sessment and their physiological pain re-
The authors report no conflict of interest.
sponse during the first 72 hours after birth
according to their mode of delivery.
individual’s response to stress stimuli
Medicine, University Hospital of Bern,Effingerstrasse 102, CH-3010 Bern,
consequences in later life. Hypertension,
MATERIALS AND METHODS Study design and population
and a higher susceptibility for depression
Population
2012 Mosby, Inc. All rights reserved.
In this national, prospective, multicenter
MONTH 2012 American Journal of Obstetrics & Gynecology 1.e1
Research Basic Science: Obstetrics www.AJOG.org
cubation period of 48 hours at 4°C, plates
nurse. At the age of 72 hours, the expres-
2010 that ended in elective cesarean sec-
sion of the neonates’ pain was assessed 30
tion, spontaneous vaginal delivery, or as-
seconds before and at least 2 minutes af-
sisted vaginal delivery by vacuum extrac-
tion. Exclusion criteria were delivery less
Guthrie test by a trained staff nurse, doc-
than 35 weeks of gestation, use of opiates
incubated for 48 hours at 4°C. Synthetic
for pain relief during labor, birthweight
saliva mixed with cortisol in a range from
0 to 100 nmol/L served as standards.
samples were given in duplicate wells.
reaction, we statistically tested characteris-
tics of the birth process like the use of epi-
niotic fluid, or long duration of the first
cortisol and 2 validated pain scores.
biochemical stress response, the NB’s sa-
tutional review board of all 3 participat-
liva cortisol was collected before and af-
lution induced the fluorescence, which can
study did only measure the NBs’ clinical
Statistical analysis
pain reaction and did not collect cortisol
was calculated. The intraassay coefficient
ery, the baseline characteristics of the de-
liveries, and the neonates were statistically
analyzed. Continuous data were calculated
by 1-way analysis of variation in which the
distribution was normal. When testing for
under the infant’s tongue for 2 minutes.
normality failed, Kruskal-Wallis was used.
cortisol levels, the less invasive proce-
Posttesting correction with Bonferroni’s
minutes after the prick, and the material
and Dunn’s test was used. Categorical data
was then sent to a certified external lab-
were evaluated by 2 test or Fisher exact
saliva samples were stored at Ϫ20°C un-
gression analysis. All statistical calcula-
til analysis. After thawing, saliva samples
were centrifuged at 2000 ϫ g for 10 min-
Stat 3.0 (GraphPad, San Diego, CA). P Ͻ
.05 was considered statistically significant.
heart and breathing rate of the newborn.
croliters of saliva were used for duplicate
ery. The assisted vaginal delivery by vac-
lac). Ninety-six-well Maxisorb microtiter
EDIN Scale assessment at the age of 2, 4,
est number of primiparous women (P Ͻ
1.e2 American Journal of Obstetrics & Gynecology MONTH 2012 www.AJOG.org Basic Science: Obstetrics Research Baseline characteristics of mothers and the birth process One-way ANOVA/Kruskal- If significant: posttest: Wallis/2 test/Mann- Bonferroni/Dunn’s/ Characteristic (n ؍ 112) SVD (n ؍ 107) VE (n ؍ 61) Whitney test Fisher exact test
500 (200-1500) 300 (150-1500) 350 (200-2000) Ͻ .0001
. ANOVA, analysis of variance; BMI, body mass index; ELSC, elective cesarean section; SVD, spontaneous vaginal delivery; VE, vacuum extraction. a Normality test not passed, values in median (range), calculated by Kruskal Wallis, if significant posttest: Dunn’s; b Categorical data (if 2 significant, posttest: Fisher exact test: SVD und VE);
c Significant difference between ELCS and SVD (P Ͻ .001) and between ELSC und VE (P Ͻ .001) and between SVD and VE (P Ͻ .05); d Significant difference between ELSC und SVD (P Ͻ .001)
and between ELSC und VE (P Ͻ .001); e Categorial data (2 test). Schuller. Pain response of neonates according to their mode of delivery. Am J Obstet Gynecol 2012.
.0001) and highest proportion of potential
tistically significant, they probably are of
stress factors during labor like elevated
blood loss (P Ͻ .05), more frequent use of
group, but this was not statistically sig-
analgesia (P Ͻ .0001), and a higher per-
(17.14%) had at least 1 positive score at
centage of nonreassuring fetal heart rate
the particular time points of the serially
tisol values after heel prick rose in all of
(P Ͻ .0001). A longer interval between
(P Ͻ .001), nonreassuring fetal heart rate
(P Ͻ .0001), and a longer duration of the
statistically significant (P ϭ .2420).
first (P ϭ .0014) and second stages of la-
bor (P Ͻ .0001) were more frequent in
before and after the Guthrie rest regard-
ing the Bernese Pain Scale (P ϭ .054, P ϭ
were statistically significant (P ϭ .0022
this difference was not statistically signif-
and P ϭ .0016, respectively).
vealed that only the presence of meconium-
cortisol values were almost equal in all 3
Guthrie test (P ϭ .179). However, after
hours, P ϭ .011, EDIN 2-24 hours, P ϭ
.031). All the other intrapartum features
(use of regional analgesia, length of sec-
cesarean section (ELCS), respectively, in
ond stage of labor, interval between rup-
minutes. Although these results were sta-
tion to the stress response and pain reac-
MONTH 2012 American Journal of Obstetrics & Gynecology 1.e3
Research Basic Science: Obstetrics www.AJOG.org
ference is small and statistically nonsig-
nificant. This might be due to their phys-
Baseline characteristics of neonates Characteristic ELSC (n ؍ 112) SVD (n ؍ 107) VE (n ؍ 61)
during labor known as fetal inhibition.
cortisol levels differed among groups ac-
. Statistical significant difference between all outcome parameters of the neonates of the 3 groups: P ϭ .0015 for Apgar 1
minute; P ϭ .0009 for Apgar 5 minutes; P ϭ .0195 for Apgar 10 minutes; P Ͻ .0001 for pH value cord artery; P ϭ .0024
for pH cord value vein. ELSC, elective cesarean section; F, female; M, male; SVD, spontaneous vaginal delivery; VE, vacuum extraction.
a Normality test not passed values in median (range); b Normality test passed, values in mean [SD].
statistically significant. These findings
Schuller. Pain response of neonates according to their mode of delivery. Am J Obstet Gynecol 2012.
correspond to the data of other studieslooking at the time immediately after
tion of the neonates during the entire ob-
different behavioral as well as biochemi-
were no clear alterations of the modified
Bernese Pain Scale to be noted before but
have a direct clinical implication and are
lance of 72 hours after birth, we can con-
pression. In our study, the most signifi-
response and also clinical pain reaction,
first 24 hours of surveillance after birth.
proportion of children is the most stress-
During this very first period of their life,
subjectively. Indicators of neonatal pain
children of the ELCS group, but this dif-
touse clinically recovers after a period of
Number of positive EDIN scores (>7) If significant (n ؍ positive (n ؍ positive (n ؍ positive posttest: Fisher Variable (n ؍ total) (n ؍ total) (n ؍ total)
2 test exact test
. Categorical data (if 2 test significant, posttest: Fisher exact test: between SVD und VE). EDIN, Échelle de Douleur Inconfort Nouveau-Née, Neonatal Pain and Discomfort Scale; ELSC, elective cesarean section; SVD, spontaneous vaginal delivery; VE, vacuum extraction. Schuller. Pain response of neonates according to their mode of delivery. Am J Obstet Gynecol 2012.1.e4 American Journal of Obstetrics & Gynecology MONTH 2012 www.AJOG.org Basic Science: Obstetrics Research Bernese Pain Scale and saliva cortisol 72 h post partum Variable ELSC (n ؍ 112) SVD (n ؍ 107) VE (n ؍ 61) Kruskal-Wallis
. ELSC, elective cesarean section; SVD, spontaneous vaginal delivery; VE, vacuum extraction. a Normality test not passed; values in median (range) calculated by Kruskal Wallis; b Significant difference between VE and ELSC (P Ͻ .05) but not between VE und SVD (P Ͼ .05) posttest: Dunn’s. Schuller. Pain response of neonates according to their mode of delivery. Am J Obstet Gynecol 2012.
the infant during the peripartum period.
ery has a positive long-term effect of the
ever, when we measure the saliva cortisol
of the NBs after the heel prick for Guth-
ACKNOWLEDGMENTS
rie test, the physiological reaction to a
We give special acknowledgments to N. Schöbiund K. Jost, who made substantial contribu-
tions to the acquisition of data at University
children exposed to elevated cortisol lev-
Hospital Basel (Basel, Switzerland) and Univer-
birth. This observation is remarkable, and
sity Hospital Zürich (Zürich, Switzerland). C.S.
we must presume that vaginal birth, espe-
made substantial contributions to the study de-
cially VE for some children, can be consid-
sign, drafted the manuscript, and made sub-stantial contributions to acquisition, analysis,
erable not only short-living trauma with a
and interpretation of data. N.K. made substan-
tial contributions to acquisition, video recording,
stress or pain stimuli later in life with a
born after elective cesarean section with-
and analysis and interpretation of data and re-
higher physiological stress response.
vised the manuscript critically for important in-
by cesarean section at onset of labor or at
tellectual content. O.M. ex aequo made sub-
stantial contributions to acquisition, videorecording, and analysis and interpretation of
terms of elevated cortisol levels at vaginal
cause elective cesarean section in our set-
data and revised the manuscript critically for
important intellectual content. I.H. and E.M.T.
later on the occasion of neonatal circum-
made substantial contributions to acquisition of
group with cesarean after onset of labor.
data and financial support and revised the man-
uscript critically for important intellectual con-
tually be addressed in future studies.
tent. R.Z. and A.B.K. made substantial contri-butions to acquisition of data and revised the
manuscript critically for important intellectual
content. D.S. made substantial contributions to
the study design, acquisition, analysis, and in-
terpretation of data, and revised the manuscript
HPA with all its potential health hazards
critically for important intellectual content.
for the affected child. Yet the long-term
REFERENCES 1. Fletcher AB. Pain in the neonate. N Engl
niotic fluid as an intrapartum stress fac-
further investigation. In particular, the
2. Anand KJ, Hickey PR. Pain and its effects in
expression during the first 24 hours after
the human neonate and fetus. N Engl J Med
delivery but was no longer relevant for all
ated) pain response on health later in life
3. Wolf AR. Pain, nociception and the develop- ing infant. Paediatr Anaesth 1999;9:7-17.
dividuals. Until such data are available, it
4. Stevens B, Johnston C, Petryshen P, Taddio
is not possible to conclude that elective
A. Premature Infant Pain Profile: development
mode of delivery is the main stressor for
cesarean section itself as mode of deliv-
and initial validation. Clin J Pain 1996;12:13-22.
MONTH 2012 American Journal of Obstetrics & Gynecology 1.e5
Research Basic Science: Obstetrics www.AJOG.org 5. Grunau RV, Craig KD. Pain expression in ne- 14. Welberg LA, Seckl JR, Holmes MC. Prena-
concentrations and small sample volumes.
onates: facial action and cry. Pain 1987;28:
tal glucocorticoid programming of brain cortico-
Scand J Clin Lab Invest 2001;61:287-91.
steroid receptors and corticotrophin-releasing
23. Lidow MS. Long-term effects of neonatal 6. Glover V, Fisk NM. Fetal pain: implications for
hormone: possible implications for behaviour.
pain on nociceptive systems. Pain 2002;99:
research and practice. Br J Obstet Gynaecol
15. Gitau R, Menson E, Pickles V, Fisk NM, 24. Loizzo A, Loizzo S, Capasso A. Neurobiol- 7. Cignacco E, Mueller R, Hamers JP, Gessler
Glover V, MacLachlan N. Umbilical cortisol lev-
ogy of pain in children: an overview. Open
P. Pain assessment in the neonate using the
els as an indicator of the fetal stress response to
Bernese Pain Scale for Neonates. Early Hum
assisted vaginal delivery. Eur J Obstet Gynecol
25. Taddio A, Katz J, Ilersich AL, Koren G. Ef-
fect of neonatal circumcision on pain response
8. Debillon T, Zupan V, Ravault N, Magny JF, 16. Mears K, McAuliffe F, Grimes H, Morrison
during subsequent routine vaccination. Lancet
Dehan M. Development and initial validation of
JJ. Fetal cortisol in relation to labour, intrapar-
the EDIN scale, a new tool for assessing pro-
tum events and mode of delivery. J Obstet
26. Lewis M, Thomas D. Cortisol release in in-
longed pain in preterm infants. Arch Dis Child
fants in resonse to inoculation Child Dev 1990;
17. Vogl SE, Worda C, Egarter C, et al. Mode of 9. Runefors P, Arnbjörnsson E, Elander G, Mi-
delivery is associated with maternal and fetal en-
27. Owens ME, Todt EH. Pain in infancy: neo-
chelsson K. Newborn infants’ cry after heel-
docrine stress response. BJOG 2006;113:441-5.
natal reaction to a heel lance. Pain 1984;20:
prick: analysis with sound spectrogram. Acta
18. Miller NM, Fisk NM, Modi N, Glover V.
Stress responses at birth: determinants of cord
28. Lindsay RS, Lindsay RM, Waddell BJ, Seckl 10. Kapoor A, Dunn E, Kostaki A, Andrews MH, Matthews SG. Fetal programming of hypo-
arterial cortisol and links with cortisol response
JR. Prenatal clucocorticoid exposure leads to
thalamo-pituitary-adrenal function: prenatal
offspring hyperglycaemia in the rat: studies with
stress and glucocorticoids. J Physiol 2006;
19. Bird JA, Spencer JA, Mould T, Symonds ME.
the 11 beta-hydroxysteroid dehydrogenase in-
Endocrine and metabolic adaptation following
hibitor carbenoxolone, Diabetologia 1996;39:
11. Henry C, Kabbaj M, Simon H, Le Moal M,
caesarean section or vaginal delivery. Arch Dis
Maccari S. Prenatal stress increases the hypo-
Child Fetal Neonatal Ed 1996;74:F132-4. 29. Lindsay RS Lindsay RM, Edwards CRW,
thalamo-pituitary-adrenal axis response in
20. Taylor A, Fisk NM, Glover V. Mode of deliv-
Seckl JR. Inhibition of 11 beta-hydroxysteroid
young and adult rats. J Neuroendocrinol 1994;
ery and subsequent stress response. Lancet
dehydrogenase in pregnant rats and the pro-
gramming of blood pressure in the offspring. 12. Clarke AS, Wittwer DJ, Abbott DH, Sch- 21. Bergqvist LL, Katz-Salamon M, Hertegård
neider ML. Long-term effects of prenatal stress
S, Anand KJ, Lagercrantz H. Mode of delivery
30. Levitt NS, Lindsay RS, Holmes MC, Seckl
on HPA axis activity in juvenile rhesus monkeys.
modulates physiological and behavioral re-
JR. Dexamethasone in the last week of preg-
sponses to neonatal pain. J Perinatol 2009;
13. Meaney MJ, Szyf M, Seckl JR. Epigenetic
coid receptor gene expression and elevates
mechanisms of perinatal programming of hypo-
22. Nelson N, Arbring K, Theodorsson E. Neo-
thalamic-pituitary-adrenal function and health.
natal salivary cortisol in response to heelstick:
method modifications enable analysis of low
1.e6 American Journal of Obstetrics & Gynecology MONTH 2012
Oxidative Stress Responses in Older Men during Endurance Training and Detraining IOANNIS G. FATOUROS1, ATHANASIOS Z. JAMURTAS2, VASILIKI VILLIOTOU3, SOFIA POULIOPOULOU3,PANAGIOTIS FOTINAKIS1, KIRIAKOS TAXILDARIS1, and GEORGE DELICONSTANTINOS3 1Democritus University of Thrace, Department of Physical Education and Sport Science, Komotini, GREECE; 2Universityof Thessaly, Department of Physical
Fundamento científico-biológico Evolución SM ediciones REVISIÓN CIENTÍFICA-BIOLÓGICA DE LIBRO CIENCIAS 1 Dra. Alejandra Huerta-Zepeda Raúl Valadez, Rocío Téllez, Alejandra Alvarado Serie Caleidoscopio Evolución Secundaria México, 2006 184 pp . Bloque 4. Reproducción. Introducción La valoración de este libro pretende hacer un análisis de los fundament