Pain Assessment in Neonates at a Tertiary Care Center: A Prospective Observational Study

Background: Neonates may experience pain from various procedures during the hospital stay.

Aims: This study aimed at quantifying neonatal pain during six different procedures, namely, heel prick, IV sampling, IV cannulation, removal of adhesive tapes, lumbar puncture and oropharyngeal suction. 

Study Design: Prospective observational study

Subjects: All inborn and out born neonates (0-28 days) admitted in neonatal intensive care unit (NICU) or in special newborn care unit (SNCU) with gestational age between 24 – 40 weeks, who underwent any of the six painful procedures. 

Outcome measures: Study was carried out on the term and preterm neonates during various NICU procedures which cause pain without applying any interventions. For each subject, each procedure was observed only once. Addition of the scores was done according to PIPP-R Scale (Total score = Sub-total score + Gestational age score + Baseline behavioral state score). Scores in the term and preterm neonates were compared.

Results: In our study, SFD (small for date) neonates showed more sensitivity to pain as compared to AFD (appropriate for date) and LFD (large for date) neonates. There was no significant difference observed in terms of gender. Preterm neonates showed more sensitivity to pain than the term neonates. Amongst all procedures, lumbar puncture was considered the most painful and oropharyngeal suction was the least.

Conclusions: Preterm neonates are more sensitive to pain than term neonates. With the help of proper pain assessment protocol, pain in preterm neonates should be assessed to prevent long-term consequences due to early life pain.

“Pain” is defined as an unpleasant sensation which is conveyed to the brain by sensory neurons, associated with actual or potential tissue damage [1]. Neonates may experience more than 300 painful procedures and surgeries throughout their hospitalization. It has been well established that newborns can detect, process, and respond to painful stimuli. Preterm neonates are even more sensitive to pain and at greater risk for pain due to immature pain inhibition mechanisms at birth. Excessive and prolonged painful events in neonates cause adverse physiological effects in all major organ systems, which can be life threatening and have long-term effects. However, interventions to alleviate neonatal pain remain inadequate and inconsistently applied. Only half of the painful procedures performed in neonates were treated, with a wide variation of pain management [2].Early exposure to painful procedures can negatively impact neurodevelopment, such as brain growth, which is directly related to cognition. There is a strong association between exposure to painful procedures and altered behavioural development trajectories [3]. Survivors of early repetitive pain may develop attention-deficit disorders, atypical behaviours, such as hypervigilance and exaggerated startled responses, and other forms of long-term stress-related psychosocial disabilities [4]. Pain assessment is significantly important because adequate recognition of pain is essential to properly address the needs of each infant to allow safe and compassionate care.

Study design and setting

This was a prospective observational hospital-based study conducted at a tertiary care hospital in western India. All inborn/outborn neonates (0-28 days) admitted in NICU/SNCU of gestational age 24 – 40 weeks, undergoing any of the below listed painful procedures- Heel prick, IV sampling, IV cannulation, Removal of adhesive tapes, Lumbar puncture, Oropharyngeal suction, only after parental consent were included in the study.

Patients undergoing anticonvulsant therapy, sedation therapy, with congenital CNS or facial malformations, were excluded from the study.

Sample size 

Assuming the expected population standard deviation to be 2, and employing t-distribution to estimate sample size, the study required a sample size of 19, to estimate the mean with 95% confidence and a precision of 1. As we included 6 different procedures, total 120 patients were included in our study accordingly.

Data collection and definitions

Total 120 neonates were enrolled in study and 6 procedures were included: Heel prick, IV sampling, IV cannulation, Removal of adhesive tapes, Lumbar puncture, Oropharyngeal suction. Each procedure enrolled 20 neonates. Written and informed consent was obtained from the parents. A detailed history including antenatal history, birth history and postnatal history was obtained. Gestational age was calculated by New Ballard’s score. Baby was assessed for nutritional status (AFD, SFD and LFD) with the help of weight vs gestational age chart. 

Each neonate was observed for 15 seconds just before the procedure (at rest), and vital sign indicators [HR, oxygen saturation (SPO2)] details were noted by monitor and probe (model: Schiller TRUSCOPE ELITE – A5TM) attached to neonate. Behavioral state and activity were also observed. Neonate was observed for 60 seconds during the procedure (the highest HR, lowest oxygen saturation (SPO2) and duration of facial actions) and the scoring was done accordingly. Whole procedure was recorded on a mobile phone. Recordings were later analyzed using Premature Infant Pain Profile- Revised (PIPP – R scale) and PIPP – R scores were counted. 

PIPP-R Scale [5]

The original 7 items are retained in the PIPP-R: Heart rate; Oxygen saturation; Eye squeeze; Naso-labial furrow; Gestational age (GA); Baseline behavioral state (BS). The 2 contextual variables, GA and BS, were assigned at baseline before the infant was handled. The infants in the youngest GA category and those in quiet sleep states received the highest score of “3” (on the 0 to 3 scale) for these variables; thus, could obtain a total score of “6” (6 out of a possible 21) before any response to pain.

Facial expressions: Categorized by Indicator score, assessed by three parameters: Brow bulge, Eye squeeze and Nasolabial furrow. Baseline behavioral state was obtained by observing child before procedure. Addition of the scores was done according to PIPP-R Scale (Total score = Sub-total score + Gestational age score + Baseline behavioral state score), Maximum scores for term babies were 18, and for preterm babies it was 21.

Outcome measures

Study was carried out on the term and preterm neonates during various NICU procedures which cause pain without applying any interventions. For each subject, each procedure was observed only once. Standardization of non-pharmacological as well as pharmacological interventions was not present, so they were not included in the study. Addition of the scores was done according to PIPP-R Scale (Total score = Sub-total score + Gestational age score + Baseline behavioral state score). Scores in the term and preterm neonates were compared.

Statistical analyses

Software used for statistical analysis was MedCalc (11.5 version) and Excel data analysis tool pack. P values less than 0.05 were considered statistically significant.

Comparison of pain between SFD, AFD, LFD neonates in relation to growth

Table 1: SFD, AFD, LFD neonates

Overall comparison of pain in all SFD, AFD and LFD neonates

Table 2: Growth and pain interpretation in all SFD, AFD and LFD neonates

Mean score of pain observed in SFD neonates was 10.6 and in AFD neonates it was 6.7. Highly significant difference was observed statistically between means of SFD neonates & AFD neonates when paired t test was applied. (Calculated t value > reference table value) with 59 degree of freedom and 95% confidence level using 85% power of study (p value < 0> reference table value) with 59 degree of freedom and 95% confidence level using 85% power of study (p value less than 0.05). Mean score of pain observed in SFD neonates was 10.6 and in LFD neonates it was 3. Highly significant difference was found statistically between means of SFD neonates & LFD neonates when paired t test was applied (calculated t value > reference table value) with 59 degree of freedom and 95% confidence level using 85% power of study (p value less than  0.05).

Interpretation: Statistically significant difference was observed between mean pain scores of SFD and AFD as well as SFD and LFD. We can correlate above findings as, in our study, most of the preterm neonates included were SFD and most of the term neonates included in our study were AFD and LFD. 

Comparison of pain in preterm neonates

Table 3: Pain interpretation in preterm neonates

Comparison of pain between early preterm and mid preterm neonates

Mean score of pain observed in early preterm neonates was 12.5 and in mid preterm neonates, it was 11.8. The difference was statistically insignificant between means of early preterm neonates & mid preterm neonates when paired t test was applied (calculated t value < reference>

Comparison of pain between mid-preterm and late preterm neonates

Mean score of pain observed in mid preterm neonates was 11.82 and in late preterm neonates, it was 9.86. Statistically, significant difference was observed between means of mid preterm neonates & late preterm neonates when   paired t test was applied (calculated t value > reference table value) with 59 degree of freedom and 95% confidence level using 85% power of study (p value less than  0.05).

Interpretation: As maturity increased, pain scores decreased. Hence, Maturity is inversely proportional to pain scores.

Comparison of pain in term and preterm neonates

Table 4: Pain interpretation in preterm and term neonates

As described in table 4, out of 60 term neonates, 37(61.6%) had no pain, 19(31.6 %) had mild – moderate pain and 4(6.6%) had severe pain. Among 60 preterm neonates, 7(11.6%) had no pain, 32(53.3%) had mild – moderate pain and 21(35%) had severe pain. Mean score of pain observed in term neonates was 5.9 and in preterm neonates it was 10.83. Highly significant statistical difference was observed between means of term neonates & preterm neonates when paired t test was applied (calculated t value > reference table value) with 59 degree of freedom and 95% confidence level using 85% power of study (p value less than 0.05).

Comparison of pain scores between procedures

Table 5: Comparison of pain in procedures

Interpretation: Lumbar puncture was the most painful procedure and Oropharyngeal suction was the least painful procedure according to pain scores.

This study was a prospective observational hospital-based study, which included all inborn/outborn neonates (0-28 days) admitted in NICU/SNCU with gestational age 24 – 40 weeks who underwent any of the 6 painful procedures. Out of total 120 neonates enrolled, 50% were term and 50% were preterm neonates. In growth wise distribution, 45.8% neonates were SFD, 50.8% neonates were AFD and 3.4% neonates were LFD. There was a statistically significant difference observed between pain scores of SFD and AFD neonates as well as SFD and LFD neonates. During comparison of pain scores between overall term and preterm neonates, highly significant difference was observed statistically. In preterm neonates, highly significant difference was observed between pain scores of late preterm neonates and early preterm neonates. During comparison of pain scores in all 6 procedures, again highly significant difference was noted between term and preterm neonates. We also observed that, most of the neonates showed severe pain during lumbar puncture amongst all procedures and no pain during oropharyngeal suction. A commonly attempted procedure is removal of adhesive tapes in all NICUs. According to our study, most of the neonates showed mild to moderate pain response.

Total 120 neonates were included in our study out of which, 60 were term ( less than36 weeks) neonates and 60 were preterm ( less than 36 weeks) neonates. 

Total 7 indicators were included for assessment of pain by Premature Infant Pain Profile- Revised (PIPP – R) Score as listed below: Change in heart rate; Change in Oxygen Saturation; Brow bulge; Eye squeeze; Nasolabial furrow; Gestational age; Behavioral state.

PIPP – R (Revised) Scale was used as a pain assessment tool in our study. It is newly developed, validated and reliable pain assessment scale for term as well as preterm neonates. PIPP – R (Revised) score is derived from the bases of PIPP scores. Various studies have been performed to check the validity and reliability of PIPP scores. A prospective observational study was conducted by Bhaswati Ghosha on “Validity and Reliability of New Indian Neonatal Pain Score for Detecting Acute Procedural Pain in Newborn” which was published in Saudi Journal of Medical and Pharmaceutical Sciences [6]. PIPP score was used as a pain assessment tool. The study concluded that, PIPP is a multidimensional pain score which includes both behavioral (facial expression, crying, gross motor movement, changes in behavioral state and functioning) and physiologic indicators (e.g., heart rate, blood pressure, etc.). Even though these two dimensions do not correlate, yet when they coexist in a single pain scale, its importance is increased. This study was formulated to produce a multidimensional pain score in Indian scenario and had good content validity as it had covered all domains of pain sign. The PIPP score has good discriminant validity as, it is able to differentiate pain –no pain situation and has good concurrent validity as well because, it has good sensitivity and specificity to detect pain. The PIPP score is validated by looking at factor structure of the scoring system –as a measure of construct validity, which was taken and considered as a base in our study.

Contrary to this, an observational study of “Pain profile of premature infants during routine procedures in neonatal intensive care” was carried out by S. Nimbalkar et al. [7]. Pain assessment was done using PIPP score. As a result, they stated that PIPP scores vary from region to region and from NICU to NICU, if regional reference values for PIPP scores are established for each region, PIPP scores can be compared between routine procedures in various NICUs, and therefore PIPP scores can be established as a quality indicator of a particular unit. 

A complex study “The Premature Infant Pain Profile: Evaluation 13 Years After Development” done by Bonnie Stevens et al. [8] reviewed the reliability, validation, feasibility, and clinical utility and the use of the Premature Infant Pain Profile (PIPP) to determine the effectiveness of pain management strategies. This review of studies supported the PIPP as a reliable, valid, feasible, and clinically useful measure for detecting differences in clinical outcomes. They also concluded that, composite measures such as the PIPP (which included both behavioral and physiological indicators) may offer more breadth for pain assessment whereas multidimensional behavioral measures may provide greater depth in a particular dimension of pain indicator (e.g., facial activity). This study showed that, the use of PIPP score was only reliable and valid with acute procedural and postoperative pain, but not for chronic and long-lasting pain.

A study to check the initial validation and feasibility of PIPP – R score which is the pain assessment tool in our study was conducted by Bonnie J. Stevens et al [8]. The overall outcome of the study resulted into satisfaction with PIPP-R in terms of feasibility particularly in regard to ease of use and clarity of terms. PIPP and PIPP – R were highly correlated because the 7-item structure of the measures remained unchanged. However, when the pain scores of ELGA (Extremely low gestational age) infants were examined, PIPP – R scores were significantly different from PIPP scores specifically when there was no behavioral and physiological response after the painful stimulus. These results reinforced the appropriateness of weighting of the contextual variables of GA (Gestational age) and BS (Behavioral state) when computing PIPP-R scores. In addition to this, PIPP-R is a more accurate score of the infant’s pain response and avoids a falsely elevated score based on static variables at baseline when the infant does not respond. Also, the PIPP-R standardizes the scoring approach across all gestational ages, making interpretation of pain response more meaningful. The PIPP is a well-validated measure used to assess pain in preterm and term infants, but lacks sufficient data on its feasibility and clinical utility and validity with the ELGA infants. The PIPP-R is reported to be easier to use and score in clinical practice and has preliminary construct validation and feasibility. The revised measure clearly identifies which infants are not responding to pain.

A study “Psychometric Testing of the Turkish Version of the Premature Infant Pain Profile Revised-PIPP-R”done by Ayşe ŞenerTaplaket al.[9] was conducted to measure the reliability of PIPP – R scale. And as a result, the scale was found to be highly reliable. Study concluded that, the scale is composed of 3 factors: physiological, behavioral and contextual factors. In addition, the scale is considered selective in measuring the pain of neonates of different gestational age and sensitive in distinguishing between painful and painless procedures.

Our study began with distribution of the neonates into different groups as described below-As described in table 2, we distributed neonates into AFD, SFD and LFD neonates. Here, we compared pain scores between AFD, SFD and LFD neonates. Statistically significant difference was observed between mean pain scores of SFD and AFD as well as between SFD and LFD. That happened because, in our study most of the preterm neonates included were SFD and most of the term neonates included were AFD and LFD (according to table 1).

As described in table 3, we have distributed preterm neonates into 3 groups

In our study, we have compared pain scores between 3 groups of preterm neonates. Statistically insignificant difference was observed between means of early preterm neonates and mid preterm neonates but statistically significant difference was observed between means of mid preterm neonates and late preterm neonates. So, it was concluded that, pain scores decreased with the increasing maturity. Hence, maturity is inversely proportional to pain scores. Similar findings were observed in a study “Validation of the Persian Version of Premature Infant Pain Profile-Revised in Hospitalized Infants at the Neonatal Intensive Care Units” by Atousa Sadeghi et al. [10]. The pain scores both in response to the painful procedure (heel prick) and the non-painful procedure (changing diaper) was higher in infants with gestational age of less than 28 weeks, which correlated with our findings in comparison of pain scores in preterm neonates mentioned above.

The above-mentioned study by Atousa Sadeghi et al corelated with another study “Psychometric Testing of the Turkish Version of the Premature Infant Pain Profile Revised-PIPP-R” done by Ayşe Şener Taplaket et.al. [9] during the heel lance procedure, a statistically significant difference was observed between the different gestational age groups. It was determined that, the highest scores were observed in the youngest infant group (26–31 weeks) for both the painful and the painless procedures which was similar with our findings in comparison of pain scores in preterm neonates. It was reported that, there was a correlation between the gestational age and pain scores. Above study is contradicted by a study on “Comparison of pain responses in infants of different gestational age” carried out by Sharyn Gibbins et al. [11] where NFCS Scoring system was used for pain assessment. The responses were directly proportional to gestational age with the youngest infants ( less than 27 6/7 weeks) showing the least response. The conclusion was that, ELGA infants have similar pain responses to older infants but, responses were dampened in NFCS coding system. In above mentioned study by Sharyn Gibbins et al, preterm neonates showed a smaller number of facial changes as compared to term neonates. Conclusion of this study was contrary to our study because, gestational age is not considered as a factor in NFCS coding system as in PIPP – R score. As mentioned in the study by Atousa Sadeghi et al. [10], pain is a subjective phenomenon, it is hard to determine its intensity and quality, especially in premature infants whose responses to pain are different due to their less developed central nervous system, gestational age is an important factor in response to pain.

In our study, we did overall comparison of pain scores between all term and preterm neonates According to table 4, highly significant statistical difference was observed between pain scores of all term neonates and preterm neonates during different procedures. Preterm neonates showed higher pain scores and higher pain perception compared to term neonates enrolled in the study. As described in a study done by Atousa Sadeghi et al. [10]as mentioned above, neonates less than 28 weeks showed highest pain scores and term infants had the lowest score in response to the painful procedure. Same results were obtained in our study during overall comparison of pain scores between term neonates and preterm neonates as described in table 4. 

Contrary to this, a clinical study “Nurses’ judgements of pain in term and preterm newborns” published in Journal of Obstetric, Gynaecologic and Neonatal Nursing (JOGNN) by Carla R. Shapiro [12], where visual analogue scale (VAS) was selected as a pain assessment tool showed that during heel lance procedure, a statistically significant difference was found in the pain scores of full-term neonates as compared to preterm neonates. Specifically higher pain ratings were assigned to full term neonates than to premature neonates. So, the findings were totally contradicted to our study. Explanation to this is, as full-term neonates were more vigorous and vocal, they cried louder and harder and as a group and were much more active than premature neonates. This concluded that more vocal and vigorous neonates got more attention and premature neonates might get deemed because they were not able to communicate their sufferings. This study was based on Visual Analogue Scale (VAS) which considered vigorousness and vocalization of a neonate as indicators of pain. As described above by Atousa Sadeghi et al. [10], pain is a subjective phenomenon, it is hard to determine its intensity and quality, especially in premature neonates whose responses to pain are different due to their less developed central nervous system. Thus, gestational age is an important factor in response to pain. PIPP – R score has considered prematurity as a factor affecting pain and included GA (gestational age) in scoring of pain. As a result, preterm neonates showed more scores compared to term neonates in our study.

Similar studies were conducted in terms of comparison between term and preterm neonates

A study on “Higher tactile sensitivity in preterm infants at term-equivalent age” by Vanessa Andre et al. [13] where body movements and facial expressions were taken as indicators for stimulation. The results of this pilot study revealed high differences in terms of tactile sensitivity in preterm, early-term and full-term neonates at term-equivalent age. Thus, premature infants showed a higher tactile sensitivity as compared to infants born near or at term. Thus, preterm infants reacted to the very light mechanical stimulation, while almost none of the early-term infants did. This study revealed 2 hypotheses: a) the higher sensitivity observed in preterm neonates could be related to postnatal experiences. During NICU stay premature neonates were submitted to numerous and various procedures, corresponding to a wide range of cutaneous sensory stimuli either light or strong/noxious. b) Preterm infants may also show a differential maturation due to an earlier stage of development of sensory system at birth. Moreover, preterm neonates have thin epidermal barrier which is more prone to exogenous material and damage. This study had a different idea of comparison of preterm neonates at their term equivalent age which we have not included in our study. But results were partly correlated with the aspects of tolerance and intensity of pain or stimulating sensations in preterm neonates. 

We included 6 procedures in our study and 20 neonates were distributed per procedure

As described in table 5, we have compared pain scores in all 6 procedures individually. Pain assessment in all procedures (heel prick, IV sampling, IV cannulation, removal of adhesive tapes, lumbar puncture and oropharyngeal suction) showed that there was highly significant difference observed statistically between the pain scores of terms and preterm neonates. Similar findings were observed in a study by Atousa Sadeghi et al. [10]. The observation of the study by Atousa et al. was that the pain score both in response to the painful procedure (heel prick) and the non-painful procedure (changing diaper) was higher in infants with gestational age of less than 28 weeks which is highly correlated with our findings in comparison of pain scores between more painful (lumbar puncture) and less painful procedure (oropharyngeal suction).

In a study by Ayşe ŞenerTaplak et al. [9], It was observed that the mean PIPP-R scores obtained in each group during the diaper changing procedure were lower than the mean scores obtained during the heel lance procedure, and a statistically significant difference was found between the mean scores which also matched to procedural pain comparison in our study. Similarly, a prospective study of “Procedural pain and analgesia in neonates” conducted by Sinno H.P. Simons et al. [14], where The Visual Analogue Scale (VAS) was used as pain assessment tool. Procedures with lower scores such as diaper change, cranial ultrasound, insertion of nasal cannula, X rays and removal of nasogastric tubes were considered less painful and all other procedures were considered moderate to severe painful. We used PIPP – R scale for comparison of procedural pain. In our study, out of 6 enrolled procedures, Lumbar puncture was the most painful procedure and oropharyngeal suction was the least painful procedure (as described in table 5). It was also observed that, 50% of neonates had mild – moderate pain response on removal of adhesive tapes. Hence, one should be very cautious while removing the adhesive tapes gently in routine care of newborns considering the amount of pain felt by the neonates.

Out of total 120 neonates enrolled in our study, 50% were term and 50% were preterm neonates. In growth wise distribution, 45.8% neonates were SFD, 50.8% neonates were AFD and 3.4% neonates were LFD. In our study, SFD neonates showed more sensitivity to pain as compared to AFD and LFD neonates because most of the preterm neonates included were SFD and most of the term neonates were AFD and LFD. During comparison of pain scores between overall term and preterm neonates, preterm neonates showed more sensitivity to pain compared to term neonates. In preterm neonates, early preterm neonates showed more sensitivity to pain than late preterm neonates, which suggested that maturity is inversely proportional to pain scores in neonates. In procedure-wise comparison of pain scores between term and preterm neonates, again preterm neonates showed more sensitivity to pain than term neonates in all 6 procedures included in our study. We also observed that, lumbar puncture was the most painful procedure amongst all procedures and oropharyngeal suction was the least painful procedure. A commonly attempted procedure is removal of adhesive tapes in all NICUs. According to our study, it showed mild to moderate pain response in neonates. Hence, one should be gentle in removing adhesive tapes in neonates. With above findings this study concludes that preterm neonates are more fragile and more sensitive than term neonates. With the help of proper pain assessment protocol, pain in preterm neonates who are less active and less vocal than term neonates should be assessed and long-term consequences due to early life pain can be prevented.

Limitations of the study

We have only included assessment of pain in our study but management and the interventions to prevent the procedural pain in neonates were not included. Long term follow- up of the neonates undergoing painful procedures is not possible in our study to check the long-term effects of pain during NICU stay. We have only included neurologically stable neonates in our study. Neonates with birth asphyxia or with CNS infections or with kernicterus were not included, as the neurological state of the neonates can affect the pain scores. However, neonates with neurological impairments do have pain, but some other validated pain assessment score can be used especially for the neurologically impaired neonates.

NICU Neonatal Intensive Care Unit, SNCU Special Newborn Care Unit, SPO2 Oxygen Saturation, PIPP-R Premature Infant Pain Profile-Revised, SFD Small for Date, AFD Appropriate for Date, LFD Large for Date

Acknowledgements

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Funding Resources

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