Stress and pain response of neonates after spontaneous birth and vacuum-assisted and cesarean delivery

Objective

The objective of the study was to compare the stress response and pain expression of newborns (NBs) in the early postpartum period.

Study Design

This was a prospective study with 280 NBs enclosed at 3 Swiss university hospitals. Stress response and pain reaction were analyzed according to the mode of delivery: elective cesarean section (ELCS), spontaneous vaginal delivery, and assisted vaginal delivery by vacuum extraction (VE). Saliva cortisol and clinical pain expression were evaluated after delivery and before and after heel prick for metabolic screening.

Results

Significant differences were evident during the first 72 hours postpartum with highest nominations in the VE group. Meconium-stained amniotic fluid was the only intrapartum stress factor with an impact on clinical pain expression.

Conclusion

NBs delivered vaginally show a higher incidence of stress response and pain expression than infants of the ELCS group. The long-term impact of these findings remains to be determined.

A few decades ago, it was scientific belief that newborns do not own the capability to perceive pain at all or only in a very restricted way. Years later, it was demonstrated in literature that the amount of nociceptive receptors in the skin of a newborn is as high as or even higher than in an adult. Nociceptive nerve tracts and neurons are fully developed in the fetus at 20-24 weeks of gestation, and the maximum metabolic activity of a newborn’s brain can be found in sensoric brain areas.

Stress and pain response of the newborn can be measured by physiological parameters like blood pressure, frequency of the heartbeat, oxygen saturation, or cortisol measurement in bodily fluids (umbilical cord blood, saliva). The expression of pain can be estimated by validated pain scores specially developed for the assessment of pain in newborns admitted to neonatal care units (Bernese Pain Scale, Échelle de Douleur Inconfort Nouveau-Née, Neonatal Pain and Discomfort Scale [EDIN] score).

Animal studies and later also clinical trials in humans have shown that stress and pain in the perinatal period causes elevated cortisol levels in newborns and thereby effectuates long-term programming of the hypothalamic-pituitary axis (HPA). Mainly in animal studies this mechanism has been proven to alter the individual’s response to stress stimuli and also revealed to have subsequent consequences in later life. Hypertension, hyperglycemia, and hyperinsulinemia and a higher susceptibility for depression are possible consequences of perinatal stress for the affected individuum.

Childbirth is considered to be the main stressor during the perinatal period. Previous literature describes a difference in the physiological stress response of children born by cesarean section as compared with those delivered spontaneously. According to these studies, the mode of delivery results in specific amounts of cortisol in blood samples taken from the umbilical cord immediately at birth.

Whether high cortisol levels after birth are linked to relevant clinical pain in the newborn is not elaborated in most previous studies. To our knowledge, there are few data available on the group of infants born by assisted vaginal delivery and on the peripartum stress response and clinical expression of pain in these children. To determine whether there is a coherence between elevated cortisol levels and the expression of relevant pain, we investigated newborns’ clinical pain assessment and their physiological pain response during the first 72 hours after birth according to their mode of delivery.

Materials and Methods

Study design and population

Population

In this national, prospective, multicenter study, we antenatally enrolled 280 singleton pregnancies between 2007 and 2010 that ended in elective cesarean section, spontaneous vaginal delivery, or assisted vaginal delivery by vacuum extraction. Exclusion criteria were delivery less than 35 weeks of gestation, use of opiates for pain relief during labor, birthweight less than 2000 g, and neonatal malformations or admission to a neonatal intensive care unit.

Methods

Pain and stress reaction of the newborns (NBs) were analyzed according to the mode of delivery. For each child, 3 outcome parameters were assessed: saliva cortisol and 2 validated pain scores.

For the measurement of the infants’ biochemical stress response, the NB’s saliva cortisol was collected before and after pain stimulation by the Guthrie test 72 hours postpartum (pp). Valid samples were analyzed from 141 of 280 NBs (50.35%). This was due to the fact that one of the centers participating in the study did only measure the NBs’ clinical pain reaction and did not collect cortisol samples from the children. In addition, some of the saliva samples collected did not contain enough material to allow cortisol measurement.

The specimens were assayed 5 minutes before the heel prick by a swab placed under the infant’s tongue for 2 minutes. The same procedure was repeated 30 minutes after the prick, and the material was then sent to a certified external laboratory for examination by DELFIA analysis (time-resolved fluorescence immunoassay with fluoromeric endpoint detection; Wallac, Turku, Finland). The saliva samples were stored at −20°C until analysis. After thawing, saliva samples were centrifuged at 2000 × g for 10 minutes, which resulted in a clear supernatant of low viscosity. One hundred microliters of saliva were used for duplicate analysis.

Cortisol levels were determined using a competitive solid-phase, time-resolved fluorescence immunoassay with flouromeric endpoint detection (DELFIA; Wallac). Ninety-six-well Maxisorb microtiter plates were coated with polyclonal swine antirabbit immunoglobulin. After an incubation period of 48 hours at 4°C, plates were washed 3 times with wash buffer (pH 7.4).

In the next step, the plates were coated with a rabbit anticortisol antibody and incubated for 48 hours at 4°C. Synthetic saliva mixed with cortisol in a range from 0 to 100 nmol/L served as standards. Standards, controls (saliva pools), and samples were given in duplicate wells. Fifty microliters of biotin-conjugated cortisol was added and after 30 minutes of incubation, the nonbinding cortisol/biotin-conjugated cortisol was removed by washing (3 times). Two hundred microliters of europium-streptavidin (Perkin Elmer Life Science, Turku, Finland) were added to each well and after 30 minutes and 6 times of washing, 200 μL enhancement solution was added (Pharmacia, Freiburg, Germany). Within 15 minutes on a shaker, the enhancement solution induced the fluorescence, which can be detected with a DELFIA fluorometer (Wallac).

With a computer-controlled program, a standard curve was generated and the cortisol concentration of the samples was calculated. The intraassay coefficient of variation was between 4.0% and 6.7%, and the corresponding interassay coefficients of variation were between 7.1% and 9.0%.

Because there is a reliable correlation between serum cortisol levels and saliva cortisol levels, the less invasive procedure was chosen for the assessment.

The EDIN scale and the modified Bernese pain score (Bernese Pain Scale for Neonates [BPSN]) are both developed for the clinical assessment of pain in newborns. They are based on the estimation of behavioral characteristics and physiological parameters. We used a modified version of the original BPSN, not enfolding the oxygen saturation and heart and breathing rate of the newborn. Although the EDIN Scale gives information about prolonged experience of pain (hours until days), the modified BPSN estimates acute pain in the newborn.

During the first 24 hours after birth, the neonates were evaluated by serial EDIN Scale assessment at the age of 2, 4, 8, 12, and 24 hours. The tests were conducted by a specially trained midwife or nurse. At the age of 72 hours, the expression of the neonates’ pain was assessed 30 seconds before and at least 2 minutes after the standardized puncture for the Guthrie test by a trained staff nurse, documented by video recording, and then also analyzed by 2 independent skilled experts applying the categories of the modified BPSN.

To discriminate the role of the presumed main stressor (mode of delivery) from other intrapartum factors with a possible impact on the peripartum stress reaction, we statistically tested characteristics of the birth process like the use of epidural anesthesia, meconium-stained amniotic fluid, or long duration of the first and second stages of labor.

The study was approved by the institutional review board of all 3 participating institutions (University Women’s Hospital of Berne, Basel, and Zürich, Switzerland). All included women gave written informed consent at enrollment prior to birth.