Our study found that preterm infants in NICU and their mothers experience stress, which is confirmed with the increased baseline cortisol levels, both in children and mothers. Extremely and very preterm neonates undergo repeated painful treatment and caregiving procedures during a period of rapid brain development and stress system programming [1, 11]. This is a period when their sensory systems are immature and thus the imbalance of excitatory versus inhibitory processes can lead to increased nociceptive signaling in the central nervous system . The immature central nervous system of preterm infants is particularly vulnerable to intensive external stimuli, and in combination with mother’s separation and pleasant stimuli absence (mother’s touch, voice, odor) has been associated with altered brain microstructure, hormonal status disbalance [11, 16]. A lot of researches showed stress related to procedural neonatal pain during heel lance, eye-screening examination, physical examination, and caregiving interventions that was associated with the increased levels of cortisol [2, 8, 17, 18]. Our study was not associated with some exact procedural pain, as the sample collection was performed against the background of all routine procedures.
The present study revealed inverse correlation between the baseline cortisol level and Apgar score at 1st and 5th minutes (r=-0.36; p = 0.011 and r=-0.34; p = 0.017), and duration of invasive ventilation (Spearman r = 0.70; p = 0.000). Low Apgar scores in premature newborns are considered to reflect more developmental immaturity than fetal distress, and such Apgar score criteria as muscle tone, reflex irritability, and respiratory effort are developmentally determined [19, 20]. As preterm neonates with low Apgar scores tend to be less mature, therefore, our results of correlations between Apgar score and cortisol levels may indicate the increased response of the preterm infant to stress due to the higher degree of immaturity . Also, preterm newborns with low Apgar scores receive primary resuscitation in the delivery room and intensive neonatal care during the first hours of life [1, 3] that can serve as an additional trigger for an intense stress response with a long-lasting effect.
To the best of our knowledge data about the correlation between Apgar score and stress intensity in preterm infants are absent. However, it is known that mortality, multisystem morbidity, incidences of neonatal interventions, and complications are significantly higher in newborns of gestational age less than 37 weeks with low Apgar score [19, 20].
The invasive ventilation period can be described as a very stressful and uncomfortable period , and the less mature the infant, the longer ventilation he/she needs . There is no data on how painful and stressful invasive ventilation is itself, but it is obvious that it is accompanied by plenty of potential painful interventions like intubation and sometimes reintubation, often endotracheal suctioning, skin lesions due to the adhesive materials changes. Routine use of sedatives seems insufficient to prevent high stress scores . Also, various modes of ventilation can potentially increase the level of stress. In particular, infants additionally suffer from the need to “fight the ventilator” at mandatory asynchronous modes . It was also shown a reduction in stress hormone concentration, namely adrenaline, over a short time period in preterm infants with gestational age less than 32 weeks when mode of ventilation was changed from conventional mandatory ventilation to patient triggered ventilation . With the wide introduction of high frequency ventilation in the neonatal practice the reports of increased stress manifestation, namely discomfort, agitation, restlessness, increased pain scores and decreased sleep time appeared in literature , however, there are no data on laboratory determination of hormonal status in children with high frequency and conventional ventilation.
Stress and pain experienced in the neonatal period have been suggested to influence the HPA axis in the later period . Thus, chronic activation of the HPA axis in early life is considered to result in long-term programming of the HPA axis to function in a dysregulated manner . Higher baseline salivary cortisol that positively correlated to the amount of experienced pain has been reported in preterm infants at eight months corrected age as compared with the full-term healthy neonates . Thus, the higher salivary cortisol level, found in the present study, could be an early sign of a disturbance in the HPA system related to stress in preterm infants in the NICU. Also, stress in preterm newborns has been associated with long-term consequences as disorders in cognitive, motor, and behavioral development, anxiety, depression, autism spectrum disorder, high blood pressure, and metabolic syndrome [12, 16, 27]. Therefore, preterm infants who had long-term mechanical ventilation and low Apgar scores require special support in stress mitigation and follow-up monitoring to prevent early and long-term effects of prolonged stress hormones elevations.
The current study showed that mothers of preterm infants in the NICU also experienced high levels of stress. These findings coincide with other researches [12, 14] that pointed the mother-infant separation and inability to perform maternal role were the greatest stress factor for mothers . Most of these studies examined the behavioral manifestations of maternal stress using questionnaires, and there are only a few data on hormonal status evaluation in mothers after preterm birth and admission of their infants to NICU [8, 12].
Increased cortisol levels in mothers who gave birth by cesarean section indicate that mode of delivery is associated with maternal endocrine stress response. Orovou et al. stated that 40% of women experienced cesarean section, especially emergency cesarean section (70%), as a traumatic childbirth experience . Some studies pointed out the emergency cesarean section as a risk factor for the development of postpartum psychological disorders [28, 29]. Several authors showed a great correlation between emergency cesarean section and posttraumatic stress disorder compared to other types of birth [30, 31].
Stress in the NICU leads to the search for evidence-based interventions that would effectively reduce stress and its negative consequences for infants and their mothers. Kangaroo Mother Care with skin-to-skin contact is one of the developmental care approaches that has been used to mitigate the physiological and behavioral stress and treat the negative consequences of maternal separations from infants . Our study provides valuable insights about laboratory confirmation of positive SSC effect on infant and maternal hormonal stress. Cortisol level decreasing in infants indicates that SSC has buffering effects on stress reactivity. Constantly receiving the warmth from the mother’s skin and familiar olfactory stimuli, having autonomic stability and calm sleep, feeling comfort and safety on mother’s chest and hear her heartbeat together with the incredible power of maternal love and tender embrace may facilitate the maturation of the HPA axis and decrease infant stress reactivity during SSC [33, 34]. Our results are consistent with the theory that maternal contact and gentle touch have an impact on the infant’s brain system that manages stress .
The stress regulatory effect of SSC was investigated by other authors. Thus, Lyngstad et al. found that SSC ameliorates the stress associated with diaper change in premature infants with gestational age 28–34 weeks . Castral et al. investigated the salivary cortisol level in infants before and after heel prick that was performed at SSC and they found no increase in the cortisol level .
Similar to research in premature infants, maternal salivary cortisol levels after SSC significantly reduced when compared with baseline levels in our study that coincides with the results of other authors [12, 36]. Decreased feelings of stress and anxiety state in mothers of preterm infants during and after SSC were also reported in the researches that studied behavioral patterns of maternal stress. Mothers often say that the inability to hold and hug the child causes the most stress. Therefore, skin-to-skin contact, which allows the mother to hold the baby on her chest, feel his/her every movement and heartbeat will undoubtedly bring the mother not only pleasure, but also will help to mitigate the negative effects of parental role alteration, enhance the feelings of the maternal parental role . Also, it has been proven that the feeling of comfort and stress reduction by mothers is continued even after SSC that confirms a prolonged effect of SSC on maternal stress [37, 38]. Therefore, it is also necessary to study the duration of the beneficial effect of SSC on maternal hormonal status.
Some infants (8.3%) and mothers (10.0%) in our study responded to SSC with the increase of cortisol levels. We have found some researches that pointed to either increased or decreased cortisol levels during the SSC - a decrease was revealed in 45.7% and an increase in 54.3% of newborns . We have much fewer “nonresponders” to stress buffer effects of SSC, which requires further study of these features. Therefore, it is valuable to identify the unique needs of each baby. According to the developmental care principles, it is important to provide the infant with opportunities for rest and recovery and to individualize the technique of this manipulation in keeping with the capabilities and needs of each child. Some babies may be ready for SSC soon after birth and others may need to have several days or even weeks in an incubator or cot because they are unwell and unstable . Each infant’s status and need should be assessed before SSC begins to ensure that the procedure is beneficial to each baby. It is also necessary to prepare the mother for this intervention and make sure that she feels confident enough to hold her infant quickly after birth, or maybe the mother will need time to learn her infant and become more comfortable with the environment .
Environmental factors, such as sharing the time and environment, are considered to increase the correlation between maternal and child cortisol levels [8, 40]. We found no significant correlations between maternal and infant cortisol levels before and after skin-to-skin contact. The lack of correlation may be explained by the fact that mothers were not constantly present with infants, did not stay overnight at the NICU, and were not involved in all caregiving procedures around the clock [8, 41]. The objective support to these data was provided by Morelius et al. who compared the influence of Family-Centered Care, when parents were constantly present with infants in relation to the standard care by measuring the salivary cortisol before and after nappy change as a stressful intervention. No significant differences regarding cortisol reactivity were found; however, there was a correlation between the basal and reactive cortisol levels in infants and mothers in the Family-Centered Care Group compared to the standard care group . It is considered that the human touch and constant closeness to the parent day and night facilitate the preterm infant biological brain development and the HPA axis maturation . These findings indicate that parents must be present and stay close to their infants to be able to cherish and support the baby, and thus, achieve the mother-infant synchronization and stress reduction.