Effect of Magnetic Auricular Acupuncture on Pain during Ophthalmic Examination of the Newborn: A Multicenter, Triple-Blinded, Randomized Controlled Study

Effect of Magnetic Auricular Acupuncture on Pain during Ophthalmic Examination of the Newborn: A Multicenter, Triple-Blinded, Randomized Controlled Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Magnetic Auricular Acupuncture on Pain during Ophthalmic Examination of the Newborn: A Multicenter, Triple-Blinded, Randomized Controlled Study Long Li, Roukeyan Tuerxun, Yajie Su, Yanli Yao, Chuangzhong Yang, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4488158/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted 4 You are reading this latest preprint version Abstract Introduction: Newborn ophthalmologicexamination is a painful procedure. Untreated pain experiences in infants have both short-term and long-term consequences, and pain control is essential. Unfortunately, non-pharmacological pain strategies are usually ineffective for complex and protracted procedures, whereas many pharmacologic agents have adverse effects. Magnetic auricular acupuncture (MAA) is a new method of pain relief that is potentially safe and effective. The objective of this study was to conduct a large definitive triple blinded randomized controlled trial of MAA for reducing pain in neonates undergoing ophthalmologic examination. The trial was registered at ClinicalTrials.gov (ChiCTR1900027474). The registration was completed on November 14, 2019. Methods : This was a multi-centerrandomized controlled trial conducted at 16 tertiary hospitals in the People’s Republic of China. Infants were eligible for participation if they were born at 26 to 42 weeks gestational age (GA) and admitted to participating NICUs during the study enrollment period, and scheduled to receive an eye examination for the first time at <44 weeks’ corrected GA. Written informed consent was obtained from parents. Infants who were critically ill, dying or receiving sedatives were excluded. Infants randomized to the intervention (MAA) group receivedmagnetic stickers applied prior to the ophthalmologic procedure. Control group infants received placebo stickers with the magnets removed. We compared the primary outcome of Premature Infant Pain Profile (PIPP) score during the procedure between the two groups. Results: A total of 408 patients were randomized, but 14 patients in each of the placebo and intervention groups did not receive ophthalmologic examination; leaving 190 patients in control group and 190 in intervention group. Infant characteristics were similar in the two groups,mean PIPP scores during eye exam were significantly lower in the intervention group compared to the control group (median (IQR): 10.00 (5.00,13.00) v 12.00 (7.00,14.00), p = 0.038). Conclusions： MAA may offer an alternate to current non-pharmacologic and pharmacologic interventions to alleviate neonatal pain. Future studies should assess the long term outcomes. Magnetic Auricular Acupuncture Neonatal pain Ophthalmic Examination PIPP scores Figures Figure 1 Figure 2 Introduction Newborn ophthalmologic examination is routinely conducted to detect retinopathy of prematurity (ROP), which is a leading cause of blindness in preterm infants [ 1 ]. However, it is a painful procedure that involves inserting a speculum to keep the eye open, and using a bright light to examine the interior of the eye. Current forms of pain management include non-pharmacologic and pharmacologic methods. Non-pharmacological strategies such as sucrose, breast-feeding and non-nutritive sucking may mitigate the discomfort from procedures that are less painful but are usually ineffective for complex and protracted procedures like ophthalmologic examinations [ 2 – 5 ]. Pharmacological methods, including paracetamol, lidocaine, opioids and other sedative agents, are more effective and most frequently used for managing neonatal pain [ 2 , 6 ]. However, many pharmacologic agents have adverse effects, including bradycardia, hypotension, respiratory depression, constipation and poor feeding. Consequently, they have to be used with care and often require intensive monitoring. Magnetic auriculoacupuncture (MAA) is a new method of pain relief that is reported to be effective in infants [ 7 ]. The procedure is both noninvasive and simple, involving the placement of small magnets on the ear before initiating a painful procedure. In 2017, Chen et al [ 8 ] conducted a small pilot study in a single-blinded, randomized controlled pilot trial of 40 infants and showed that noninvasive MAA using the Battlefield Protocol [ 9 ] was safe and feasible and produced a significant, 30% reduction in pain scores compared to placebo during a heel prick procedure. In a multi-center randomized controlled trial of 100 infants at three hospitals, Gan et al [ 10 ] reported that compared to MAA infants, those in the placebo group had significantly higher Premature Infant Pain Profile (PIPP) scores [ 11 ] during and 1 h after the ROP examination. The objective of this study was to conduct a large definitive triple blinded randomized controlled trial of MAA for reducing pain in neonates undergoing ophthalmologic examination. Methods Study Design and Population We conducted a multi-center, triple-blinded, randomized, placebo-controlled trial at 16 tertiary hospitals in the People’s Republic of China from April 17, 2020 to August 30, 2021. Participating hospitals included Children´s Hospital of Xinjiang Uygur Autonomous Region, Qinghai Red Cross Hospital, Shenzhen Maternity and Child Healthcare Hospital Affiliated to Southern Medical University, Inner Mongolia Maternal and Child Health Care Hospital, Children´s Hospital of Fudan University, First Affiliated Hospital of Anhui Medical University, The First Hospital of Jilin University, The First People’s Hospital of Yinchuan, Qingdao Maternal and Child Health Care Hospital, Affiliated Hospital of Qingdao University, Gansu Provincial Maternity and Child- Care Hospital, Dalian Municipal Women and Children´s Medical Center, Shanghai General Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine, Children´s Hospital of Chongqing Medical University, Children's Hospital Affiliated to Shandong University Jinan Children's Hospital, Children´s Hospital Affiliated to Zhengzhou University. Infants were eligible for participation if they were born at 26 to 42 weeks gestational age (GA) and admitted to participating NICUs during the study enrollment period, and scheduled to receive an eye examination for the first time at < 44 weeks’ corrected GA, and whose parents provided informed consent. Exclusion criteria included infants who were critically ill or dying or who were receiving sedatives, opioids, or muscle relaxants. Outcomes and data collection The primary outcome was the Premature Infant Pain Profile (PIPP), which is a validated tool commonly used for measuring pain intensity in infants, and was recorded 15 minutes before, during and 15 minutes after the ophthalmologic examination procedure [ 9 ]. We also recorded general behavioural state of the infant 15 minutes before the exam (e.g., sleeping, awake, agitated, or crying). Secondary outcomes included oxygen saturation, heart rate, episodes of desaturation, skin irritation, and other unanticipated adverse effects. Data were also collected on the baseline characteristics of the infant, the mother, and the delivery. These included infant sex, birth weight, GA, Apgar score at five minutes, and day of life at the time of eye exam; maternal age, primiparity, and mean parity; delivery mode; and whether the delivery was a multiple birth. Sample Size Calculation We used the report from Chen et al [ 8 ] to calculate sample size. Assuming a mean (SD) PIPP score for the control group of 8 (4.5), we estimated a sample of 252 infants (126 per treatment arm) will achieve 80% power to detect a relative 20% decrease in PIPP score for the intervention group. The two-sided two sample equal-variance t-test was used for the sample size estimation at a significance level of 0.05. To account for a possible 20% missing data due to, e.g., equipment failure, 380 infants were selected through non-randomized convenience sampling method and then were divided into intervention and control groups (190 infants in each group) through simple randomization. Randomization Written informed consent was obtained from all parents. We randomized infants to intervention and control groups using a block randomization method with block size of 4 stratified by center. Dr.Su used the website of Randomization ( http://randomization.com/ ) to generate the random allocation sequence and distributed to the unblinded clinical fellows in each sub-center before the procedure. At each site, one unblinded clinical fellow was responsible for the randomization by opening a consecutive numbered, sealed, envelope containing the study group allocation, and placing the magnetic or placebo stickers on the infant. Researchers, clinicians, outcome assessors, data analysts and parents were blinded to the treatment allocation. In the event of an infant becoming ineligible after randomization, the study was postponed and recommenced when the infant became eligible, without re-randomization. Procedure Retinal screening examinations were performed after pupillary dilation by using binocular indirect ophthalmoscopy with a lid speculum and scleral depression (as needed) to detect ROP and Congenital anomalies. Eye examinations were performed by an experienced ophthalmologist. Infants randomized to the intervention (MAA) group received noninvasive MA for at least two hours before and 30 minutes after eye exam. Magnets were placed by a clinical research fellow trained in traditional Chinese medicine (including acupuncture), on five auriculoacupuncture points on each ear according to the Battlefield Protocol [ 9 ] and infants were monitored for clinical stability (heart rate, oxygen saturation, and blood pressure) for the duration of magnet placement. The magnets are commercially available (Huatuo magnetic therapy stickers) and distributed to each hospital by the center. The magnetic stickers were applied by an un-blinded clinical research fellow trained in MAA. Infants randomized to the control group were treated exactly the same as the intervention (MAA) group except that the magnets were removed from the magnet stickers to create placebo stickers. The magnetic stickers were placed on the auriculoacupuncture points in the following order: 1) Cingulate Gyrus, 2) Thalamus, 3) Omega 2, 4) Point Zero, and 5) Shenmen (HT7) (supplementary Figure S1 ). The magnetic stickers were checked every hour by the blinded bedside nurse until after the MAA intervention was completed and, if displaced, was replaced by the un-blinded clinical research fellow. The magnetic stickers were removed before the end of the intervention period at a parent’s request or if there are any adverse events that put the infant’s health at risk. In this study, infants were allowed to receive parent-initiated interventions for pain relief; examples include skin-to-skin contact, kangaroo care, and breastfeeding. Such interventions were carried out per unit protocols and documented. Measurements Infants in both study groups were fitted with a pulse oximeter (Philips Medicin System, Germany) across the right wrist to monitor heart rate and peripheral oxygen saturation during the eye exam procedure and PIPP scoring. The PIPP score is a composite that comprises the following indicators: 1) GA (to account for physiological differences related to prematurity); 2) baseline behavioural state in the 15 seconds before the potentially painful procedure; change in 3) heart rate, and 4) oxygen saturation during the procedure (from mean value in the 15 seconds before the procedure to maximum value in the 30 seconds after the procedure); presence of a 5) brow bulge, 6) nasolabial furrow, and 7) eye squeeze during the procedure (in the 30 seconds after start of examination of the first eye) The PIPP score was measured at three time points: 15 minutes before the eye exam; during the procedure; and 15 minutes after the eye exam. To obtain the PIPP score, between 0 and 3 points are allocated for each indicator and then added together. The maximum PIPP score is 21 for preterm infants 6–12, moderate pain; >12, severe pain. Quality control We recruited 16 tertiary hospitals in China.Conducted Acunpture Workshop in 2020 at Children’s Hospital of Fudan University.Introduction of Magnetic auriculoacupuncture.Teaching how to do the Pain Score test. In addition to theoretical teaching, each fellow stuck magnetic beads on the ears of project team staff to ensure the accuracy of acupuncture points and. We played the video of venipuncture to explained each step of the PIPP score.Introduction of Acunpture Clinical Trial computer program and data Analysis.Data upload to CHNN database.Data quality contorled by coordinate centre and feedback to 16 NICUs. During the implementation of the project, we resolved any questions through the web or video conferencing. Statistical Analyses The intention-to-treat principle was applied for the data analysis. Infant characteristics were compared descriptively between the two treatment arms based on the CONSORT statement. We compared the primary outcome of PIPP score during the procedure between the two treatment arms using Wilcoxon rank sum test. The uni-variable mixed-effect linear model for repeated measures of PIPP was also conducted to examine the difference in the change of PIPP between the two treatment arms. Time, intervention group, and interaction between time and group were included in the models. The other secondary outcomes, such as heart rate, analgesia and adverse events were compared between the two treatment arms using Chi-square test or student t-test, as appropriate. The generalized linear mixed models for repeated measure of secondary outcomes were also conducted to assess the influence of acupuncture on the secondary outcome. In these models, the compound symmetry and the autoregressive covariance structures were used for the random effect (between-subject) and within-subject correlated errors, respectively. All statistical analyses were carried out in SAS version 9.4 (SAS Institute, Cary, North Carolina). A 2-sided P < 0.05 was considered significant. The study was approved by the institutional research ethics committee of each hospital. The trial was registered at ClinicalTrials.gov (ChiCTR1900027474),date of first registration 14/11/2019. Results A total of 408 patients were randomized from April 17, 2020 to August 30, 2021. Fourteen patients in each of the control and intervention groups did not have ophthalmologic examination because they were discharged (n = 25) or became critically ill (n = 3), leaving 190 patients in the control group and 190 in intervention group (Fig. 1 ). Infant characteristics were similar in the two groups (Table 1 ) except there was a higher incidence of chorioamnionitis in the intervention group. Table 1 Comparison of baseline characteristics between Acupuncture and Placebo group Characteristics Placebo Acupuncture Total Statistics Pvalue Number 204 204 408 Infant Characteristics . . Gestational Age, wk, median (IQR) 32.86 ( 30.21, 37.00) 33.00 ( 30.71, 37.93) 33.00 ( 30.50, 37.57) 0.82 0.412 Birth weight, g, mean (std) 2,085.49 ( 893.13) 2,175.75 ( 920.59) 2,130.62 ( 906.97) -1.005 0.315 Male,n/N (%) 118/ 204 ( 57.8 ) 115/ 204 ( 56.4) 233/ 408 ( 57.1 ) 0.09 0.764 SGA,n/N (%) 23/ 204 ( 11.3) 16/ 204 ( 7.8) 39/ 408 ( 9.6 ) 1.389 0.239 Inborn,n/N (%) 136/ 204 ( 66.7 ) 138/ 204 ( 67.6 ) 274/ 408 ( 67.2 ) 0.044 0.833 Day of Life at enrollment,days, median (IQR) 25.00 ( 7.00, 31.50) 22.00 ( 5.50, 32.50) 23.00 ( 7.00, 32.00) -0.141 0.888 Twin, n/N (%) 48/ 204 ( 23.5 ) 45/ 204 ( 22.1) 93/ 408 ( 22.8 ) 0.125 0.723 1 min Apgar less than 7,n/N (%) 33/ 195 ( 16.9 ) 29/ 193 ( 15.0 ) 62/ 388 ( 16.0) 0.26 0.61 5 min Apgar less than 7,n/N (%) 13/ 195 ( 6.7 ) 8/ 189 ( 4.2 ) 21/ 384 ( 5.5 ) 1.1 0.294 Maternal Characteristics . . Marriage Status,n/N (%) 203/ 204 ( 99.5 ) 201/ 204 ( 98.5 ) 404/ 408 ( 99.0 ) 1.01 0.315 University,n/N (%) 81/ 204 ( 39.7) 85/ 204 ( 41.7 ) 166/ 408 ( 40.7) 0.163 0.687 Assitant pregnancy,n/N (%) 37/ 203 ( 18.2 ) 38/ 204 ( 18.6 ) 75/ 407 ( 18.4 ) 0.011 0.917 C-section,n/N (%) 126/ 204 ( 61.8 ) 138/ 204 ( 67.6 ) 264/ 408 ( 64.7) 1.545 0.214 Uterine contraction,n/N (%) 84/ 133 ( 63.2 ) 72/ 135 ( 53.3 ) 156/ 268 ( 58.2 ) 2.658 0.103 Primigravida,n/N (%) 104/ 204 ( 51.0 ) 112/ 204 ( 54.9 ) 216/ 408 ( 52.9 ) 0.63 0.427 ROM over 24h,n/N (%) 28/ 164 ( 17.1 ) 36/ 169 ( 21.3 ) 64/ 333 ( 19.2 ) 0.959 0.328 Maternal Fever,n/N (%) 6/ 204 ( 2.9 ) 3/ 204 ( 1.5 ) 9/ 408 ( 2.2 ) 1.023 0.312 Chorioamnionitis,n/N (%) 20/ 186 ( 10.8 ) 34/ 188 ( 18.1) 54/ 374 ( 14.4 ) 4.069 0.044 Maternal Smoking,n/N (%) 0/ 198 ( 0 ) 1/ 201 ( 0.5 ) 1/ 399 ( 0.3 ) 0.988 0.32 MgSO4 usage,n/N (%) 58/ 187 ( 31.0 ) 61/ 188 ( 32.4 ) 119/ 375 ( 31.7 ) 0.089 0.766 Depression during pregnancy,n/N (%) 2/ 184 ( 1.1 ) 1/ 186 ( 0.5) 3/ 370 ( 0.8 ) 0.347 0.556 Neonatal Outcome . . RDS,n/N (%) 92/ 201 ( 45.8) 86/ 204 ( 42.2) 178/ 405 ( 44.0 ) 0.537 0.464 IVH Grade ≥ 3,n/N (%) 2/ 204 ( 1.0 ) 2/ 204 ( 1.0 ) 4/ 408 ( 1.0) 0 1 ROP Stage ≥ 3,n/N (%) 5/ 204 ( 2.5 ) 6/ 204 ( 2.9) 11/ 408 ( 2.7) 0.093 0.76 Moderate & severe BPD,n/N (%) 12/ 204 ( 5.9 ) 15/ 204 ( 7.4 ) 27/ 408 ( 6.6) 0.357 0.55 Moderate & severe HIE,n/N (%) 2/ 204 ( 1.0 ) 1/ 204 ( 0.5) 3/ 408 ( 0.7 ) 0.336 0.562 Figure 1 : The flow chart of the study Table 1 . Comparison of baseline characteristics between Acupuncture and Placebo group There was no difference in mean PIPP scores between the intervention and control groups, before and after eye exam (Fig. 2 ). However, mean PIPP scores during eye exam were significantly lower in the intervention group compared to the control group (median (IQR): 10.00 (5.00,13.00) v 12.00 (7.00,14.00), p = 0.038) (Table 2 ). Table 2 PIPP scores before, during and after ophthalmologic examination procedure Outcome Placebo Acupuncture P-value PIPP, median (IQR) . Before procedure 3.00 ( 2.00, 4.00) 3.00 ( 1.00, 4.00) 0.755 During procedure 12.00 ( 7.00, 14.00) 10.00 ( 5.00, 13.00) 0.038 After procedure 3.00 ( 2.00, 4.00) 3.00 ( 2.00, 4.00) 0.152 Table 2 . PIPP scores before, during and after ophthalmologic examination procedure Figure 2 : Mean PIPP scores before, during and after procedure There was no significant difference in heart rate, oxygen saturation, or episodes of desaturation between the intervention and control groups before, during and after eye exam (Table 3 ). Eleven infants in the control group and 9 infants in intervention group (p = 0.15) experienced skin irritation on the ear, and there were no other anticipated adverse effects. There were no differences in other pain management use between the groups. Table 3 Secondary outcomes of magnetic auricular acupuncture on pain during ophthalmic examination SaO2 < 90%,n/N (%) . Before procedure 6/ 190 ( 3.2) 12/ 190 ( 6.3) 18/ 380 ( 4.7 ) 0.147 During procedure 67/ 190 ( 35.3) 54/ 190 ( 28.4 ) 121/ 380 ( 31.8 ) 0.152 After procedure 5/ 190 ( 2.6) 4/ 190 ( 2.1 ) 9/ 380 ( 2.4 ) 0.736 Heart Rate, beats per min, mean (std) . Before procedure 144.47 ( 14.76) 142.98 ( 13.94) 143.72 ( 14.36) 0.312 During procedure 171.14 ( 22.64) 169.11 ( 21.40) 170.13 ( 22.03) 0.369 After procedure 144.39 ( 12.44) 142.47 ( 13.56) 143.43 ( 13.03) 0.151 Adverse Effect,n/N (%) . Before procedure 1/ 190 ( 0.5) 2/ 190 ( 1.1 ) 3/ 380 ( 0.8) 0.562 During procedure 26/ 190 ( 13.7 ) 17/ 190 ( 8.9) 43/ 380 ( 11.3 ) 0.145 After procedure 1/ 190 ( 0.5 ) 1/ 190 ( 0.5 ) 2/ 380 ( 0.5 ) 1 Skin irritation,n/N (%) . Before procedure 2/ 190 ( 1.1 ) 0/ 190 (0 ) 2/ 380 ( 0.5 ) 0.156 During procedure 8/ 190 ( 4.2 ) 8/ 190 ( 4.2 ) 16/ 380 ( 4.2) 1 After procedure 1/ 190 ( 0.5) 1/ 190 ( 0.5) 2/ 380 ( 0.5) 1 Desaturation,n/N (%) . Before procedure 0/ 190 (0 ) 0/ 190 (0 ) 0/ 380 (0 ) N/A During procedure 18/ 190 ( 9.5) 9/ 190 ( 4.7 ) 27/ 380 ( 7.1) 0.072 After procedure 0/ 190 (0) 0/ 190 (0 ) 0/ 380 (0) N/A Analgesia,n/N (%) . Before procedure 12/ 190 ( 6.3 ) 11/ 190 ( 5.8 ) 23/ 380 ( 6.1 ) 0.83 During procedure 9/ 190 ( 4.7 ) 12/ 190 ( 6.3 ) 21/ 380 ( 5.5 ) 0.501 After procedure 22/ 190 ( 11.6 ) 20/ 190 ( 10.5 ) 42/ 380 ( 11.1 ) 0.744 Breastfeeding,n/N (%) . Before procedure 4/ 190 ( 2.1 ) 6/ 190 ( 3.2 ) 10/ 380 ( 2.6 ) 0.522 During procedure 2/ 190 ( 1.1 ) 4/ 190 ( 2.1 ) 6/ 380 ( 1.6 ) 0.41 After procedure 16/ 190 ( 8.4) 16/ 190 ( 8.4 ) 32/ 380 ( 8.4 ) 1 Pacificer,n/N (%) . Before procedure 5/ 190 ( 2.6) 1/ 190 ( 0.5 ) 6/ 380 ( 1.6) 0.1 During procedure 6/ 190 ( 3.2 ) 6/ 190 ( 3.2 ) 12/ 380 ( 3.2) 1 After procedure 4/ 190 ( 2.1 ) 2/ 190 ( 1.1 ) 6/ 380 ( 1.6 ) 0.41 Kangaroo care,n/N (%) . Before procedure 3/ 190 ( 1.6) 4/ 190 ( 2.1 ) 7/ 380 ( 1.8) 0.703 During procedure 1/ 190 ( 0.5 ) 2/ 190 ( 1.1 ) 3/ 380 ( 0.8 ) 0.562 After procedure 2/ 190 ( 1.1 ) 2/ 190 ( 1.1 ) 4/ 380 ( 1.1 ) 1 Table 3 . Secondary outcomes of magnetic auricular acupuncture on pain during ophthalmic examination Magnets were placed on five auriculoacupuncture points on each ear according to the Battlefield Protocol.The five auricular points are stimulated sequentially in the following order on each ear: 1- Cingulate Gyrus, 2- Thalamus, 3- Omega 2, 4- Point Zero, 5- Shenmen (HT7). Using cotton plug preventing magnetic fall into external auditory canal Supplementary Figure S1 . Battlefield acupuncture protocol. Discussion To our best knowledge, this is the largest definitive trial of magnetic auricular acupuncture (MAA) pain management during ophthalmologic examination in infants, and confirms the results of previous smaller trials by Chen et al [ 8 ] and Gan et al [ 10 ]. Our results show that MAA results in a 20% reduction in PIPP scores, which is consistent with the 30% reduction reported by Chen et al [ 8 ]. There were no ill effects except for mild transient skin irritation in 4.2% (n = 16/380) of infants, who were equally distributed in the intervention and control groups. The MAA magnet stickers were cheap, easily placed by trained personnel and did not interfere with routine newborn care. It is possible that MAA may offer an alternate to current non-pharmacologic and pharmacologic interventions to alleviate neonatal pain since they remain inadequate and are inconsistently applied in many countries, including China. Pain has immediate physiologic impacts on the infant, including cardiovascular changes, behavioral changes, feeding disruption, disturbed sleep, and increased energy expenditure, and may result in prolonged need for intensive care [ 12 , 13 ]. Untreated pain experiences during hospitalization early in life may have long-term consequences, including increased pain sensitivity, decreased immune system functioning, increased avoidance behavior, and social hypervigilance [ 13 ]. Early life painful experiences in the neonatal intensive care unit (NICU) may also influence the developing gut microbiome [ 14 ], and impact development of the brain structure and function on the cortical and subcortical levels [ 15 – 18 ]. Both frontal and parietal cortex volume and thickness have been found to decrease and lead to neurodevelopmental impairment [ 17 ]. Therefore, pain control is an important part of newborn care. Non-pharmacologic methods like sucrose, breast-feeding and non-nutritive sucking are commonly used but are only marginally effective. In a randomized controlled trial conducted in four groups to evaluate the use of oral sucrose and or pacifier for reducing pain responses during neonatal eye examinations using the premature infant pain profile (PIPP) scoring system, Boyle et al [ 3 ] reported that the mean (SD) PIPP scores were 15.3 (1.9), 14.3 (1.6), 12.3 (2.9), and 12.1 (3.4) for sterile water, sucrose, pacifier, and sucrose combined pacifier groups respectively, indicating that these methods reduced pain only marginally. It is also unclear whether sucrose really produces analgesia or only modifies pain-associated expressions and behaviours [ 17 , 18 ] and its long-term effects are poorly understood. Similarly, Nayak et al’s study [ 19 ] of expressed breast milk, 10% dextrose or sterile water administered orally before ROP screening in preterm neonates similarly did not significantly alleviate pain during the procedure. The frequent use of pharmacologic agents like sedatives (e.g. diazepam) and opioids (e.g. morphine, fentanyl) may have negative consequences for neurodevelopment [ 20 ]. A clear need exists for alternative pain management techniques that are safe and effective for infants. Acupuncture is a form of non-pharmacological pain management that has been practiced for over 2000 years by Traditional Chinese Medicine (TCM) practitioners and has recently been applied to neonates [ 7 ]. It involves the insertion of very thin needles through the skin at strategic points on the body, and is based on the idea of energy (“Chi”) circulating through the body through meridian pathways. Although the mechanism of action is unknown, some speculate that it works by stimulation of the endorphin system [ 7 ]. In addition to needle acupuncture, there are also noninvasive methods such as magnetic auricular acupuncture (MAA) that involve applying small magnets to strategic points on the meridians. MAA is an attractive method for pain management in neonates who have thin sensitive skin, as it is non-invasive, affordable, portable, can easily be administered in a busy NICU setting [ 8 , 10 ]. Assessing pain is difficult and becomes even more challenging when the subjects are very young or preverbal. Because of this difficulty, and because the pharmacological forms of analgesia often used in the NICU have potentially detrimental side effects, infant pain is often neglected or poorly managed. Strategies for achieving pain management are variable, ranging from the absolute absence of pain assessment or management to protocols wherein doses, regimens, and routes of administration are not standardized. A survey of Jiangsu Province Medical Quality Control Centre NICUs found that medical and nursing staff answered basic knowledge questions about neonatal pain correctly only 38% and 39% respectively [ 21 ]. Wang et al [ 22 ] reported that infants born at 34–39 weeks GA experienced an average of 66.5 painful procedures during their hospital stay, and the pain score was highest (7.0 points) for procedures involving ophthalmic examination and percutaneous central catheter insertion. It is therefore essential for NICU staff to understand and implement both nonpharmacological and pharmacological strategies for neonatal pain relief. Limitations The study was disrupted by the Covid pandemic, which led to intermittent suspension of patient recruitment, prevention of hospital visits by parents, hospital and bed closures, staff displacement and other inconveniences. This led to repeated study starts and stops at different hospitals, the study period was prolonged and we had to abandon sequential patient recruitment in favor of convenient subject sampling. The mean GA in our study was 32.8 weeks in the control group and 33 weeks in the MAA group, with no involvement of extremely preterm infants. We did not measure the impact of acupuncture on long term outcomes, including neurodevelopment and future studies should take these knowledge gaps into account. Declarations Ethics approval and consent to participate The study received ethical approval from the ethics committee of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China(KY2019082101)，the 16 recruiting hospitals obtained approval from their hospitals. Informed consent was obtained from all parents, with the same informed consent form being used at all centres. The study was registered in Chinese Clinical Trial Registry (registration number, ChiCTR1900027474 ), date of registration 14/11/2019. The trial of MAA was performed in accordance with the Declaration of Helsinki. Consent for publication Written informed consent was obtained from all parents. Availability of data and material All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author. Competing interests The authors declare that they have no competing interests Funding Dr Lee is supported by a grant from the Canadian Institutes of Health Research. Authors' contributions Drs Li, Tuerxun, and Shoo K. Lee conceptualized and designed the trial, and contributed to interpreting the results; Drs Tuerxun and Yajie Su contributed to acquisition of data, coordinated and supervised data collection, Drs Li, Shoo K. Lee and Yancheng Wang contributed to the data analysis and interpreted the results; Drs Li, Shoo K. Lee, Laishuan Wang and Tuerxun contributed to drafting of the manuscript. All authors contributed to acquisition of data and critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Acknowledgments We thank the infants, parents, nurses, neonatologists, and other clinical staff who participated in this trial. We also thank all the recruiting hospitals involved in the study. Their help and support were invaluable since they contributed significantly to the trial’s success. We also thank Chinese Neonatal Network for technical and material support. References Zeraati H, Shahinfar J, Vashani HB, Reyhani T. Effect of Multisensory Stimulation on Pain of Eye Examination in Preterm Infants. Anesth Pain Med. 2017 Feb; 7(1): e42561. DOI: 10.5812/aapm.42561. Carbajal R, Rousset A, Danan C, et al. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA. 2008;300:60-70. EM Boyle et al. Sucrose and non-nutritive sucking for the relief of pain in screening for retinopathy of prematurity: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed (2006). Stevens B, Yamada J, Ohlsson A, Haliburton S, Shorkey A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2016;16(7):CD001069. Bueno M, Yamada J, Harrison D, et al. 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Magnetic Non-invasive Auricular Acupuncture During Eye-Exam for Retinopathy of Prematurity in Preterm Infants: A Multicentre Randomized Controlled Trial. Front. Pediatr.23 December 2020://DOI.org/10.3389. Stevens B, Johnston C, Petryshen P, Taddio A. Premature Infant Pain Profile: development and initial validation. Clin J Pain. 1996;12(1):13-22. Abdulkader HM, Freer Y, Garry EM, Fleetwood-Walker SM, McIntosh N. Prematurity and neonatal noxious events exert lasting effects on infant pain behaviour. Early Hum Dev 2008;84:351–5. Giboney Page, G. Are there long-term consequences of pain in newborn or very young Infants? J Perinatal Edu. 2004;13(3):10-18. D’Agata AL, Wu J, Welandawe MKV, Dutra SVO, Kane B, Groer MW. Effects of Early Life NICU Stress on the Developing Gut Microbiome. Dev Psychobiol. 2019 July ; 61(5): 650–660. Bajic D, Commons KG, Soriano SG. Morphine-enhanced apoptosis in selective brain regions of neonatal rats. Int J Dev Neorosci. 2013;31:258-266. Duerden EG, Grunau RE, Guo T, Foong J, Pearson A, Au-Young S, et al. Early procedural pain is associated with regionally-specific alterations in thalamic development in preterm neonates. J Neurosci 2018;38:878–86. Ranger M, Chau CMY, Garg A, Woodward TS, Beg MF, Bjornson B, et al. Neonatal pain related stress predicts cortical thickness at age 7 Years in children born very preterm. PLoS One 2013;8:. Smith GC, Gutovich J, Smyser C, Pineda R, Newnham C, Tjoeng TH, et al. Neonatal intensive care unit stress is associated with brain development in preterm infants. Ann Neurol 2011;70:541–9. Nayak R, Nagaraj KN, Gururaj G. Prevention of Pain During Screening for Retinopathy of Prematurity: A Randomized Control Trial Comparing Breast Milk, 10% Dextrose and Sterile Water. Indian J Pediatr. 2020; 87(5): 353–358. DOI: 10.1007/s12098-020-03182-6. Lee KA, Ganta N, Horton JR, Chai E. Evidence for neurotoxicity due to morphine or hydromorphone use in renal impairment: a systematic review. J Palliat Med. (2016) 19:1179–87. DOI: 10.1089/jpm.2016.0101. Jiangsu Province Medical Quality Control Centre of Neonatal Department. An investigation on the cognition of neonatal pain assessment and analgesia management among medical staff in the neonatal intensive care unit. Chinese Journal of Contemporary Pediatrics 2021,23(12):1271-1275. DOI: 10.7499/j.issn.1008-8830.2107116. Wang Yajing. The status and influencing factors of operant pain in neonatal intensive care unit. Pediatr Nursing 2019 https://DOI.org/10.1111/jspn.12281. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigureS1.Battlefieldacupunctureprotocol.png Supplementary Figure S1. Battlefield acupuncture protocol. The five auricular points are stimulated sequentially in the following order on each ear: 1- Cingulate Gyrus, 2- Thalamus, 3- Omega 2, 4- Point Zero, 5- Shenmen (HT7). Using cotton plug preventing magnetic fall into external auditory canal Cite Share Download PDF Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 17 Jun, 2024 Editor assigned by journal 16 Jun, 2024 Submission checks completed at journal 16 Jun, 2024 First submitted to journal 28 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4488158","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315184682,"identity":"9beb24db-8cf9-4db9-b2b6-c99f327ae0d3","order_by":0,"name":"Long 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University","correspondingAuthor":false,"prefix":"","firstName":"Huiqing","middleName":"","lastName":"Sun","suffix":""},{"id":315184699,"identity":"c971c745-0e1f-4b71-91bb-1e4e30805166","order_by":17,"name":"Yanchen Wang","email":"","orcid":"","institution":"Children’s Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yanchen","middleName":"","lastName":"Wang","suffix":""},{"id":315184700,"identity":"bea3f35e-7ecc-4f9b-9ff6-adb81fb00070","order_by":18,"name":"Laishuan Wang","email":"","orcid":"","institution":"Children’s Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Laishuan","middleName":"","lastName":"Wang","suffix":""},{"id":315184701,"identity":"fd383fb4-5dc9-401c-8941-8cd12abf4e85","order_by":19,"name":"Shoo K. Lee","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"Shoo","middleName":"K.","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2024-05-28 05:14:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4488158/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4488158/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-06126-1","type":"published","date":"2025-10-03T15:58:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60343391,"identity":"cf82d2ad-624f-4c92-b01a-819d361f64f3","added_by":"auto","created_at":"2024-07-15 19:15:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":141798,"visible":true,"origin":"","legend":"\u003cp\u003eThe flow chart of the study\u003c/p\u003e","description":"","filename":"Figure1Theflowchartofthestudy.png","url":"https://assets-eu.researchsquare.com/files/rs-4488158/v1/3dd3086d9c18208fa9cb3571.png"},{"id":60343393,"identity":"68c6dce9-09c1-4095-9669-d09cf8f9afdd","added_by":"auto","created_at":"2024-07-15 19:15:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33782,"visible":true,"origin":"","legend":"\u003cp\u003eMean PIPP scores before, during and after procedure\u003c/p\u003e\n\u003cp\u003eThe Y-axis represents the PIPP core, The X-axis represents different time of procedure, The blue block indicated placebo group and red block indicated acupuncture group.\u003c/p\u003e","description":"","filename":"Figure2MeanPIPPscoresbeforeduringandafterprocedure.png","url":"https://assets-eu.researchsquare.com/files/rs-4488158/v1/29c7e276fc8ee242a127b869.png"},{"id":92884031,"identity":"c314818a-b8e4-481d-9751-9c33ff80ed76","added_by":"auto","created_at":"2025-10-06 16:12:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1306948,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4488158/v1/0c7da99e-41f1-439a-bf65-82f1dbe6ab72.pdf"},{"id":60343353,"identity":"686f770a-a94c-4a5f-964d-284c53d5d633","added_by":"auto","created_at":"2024-07-15 19:15:42","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":875284,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Figure S1. Battlefield acupuncture protocol.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe five auricular points are stimulated sequentially in the following order on each ear: 1- Cingulate Gyrus, 2- Thalamus, 3- Omega 2, 4- Point Zero, 5- Shenmen (HT7). Using cotton plug preventing magnetic fall into external auditory canal\u003c/p\u003e","description":"","filename":"SupplementaryFigureS1.Battlefieldacupunctureprotocol.png","url":"https://assets-eu.researchsquare.com/files/rs-4488158/v1/50d59211b4d0a583145dfb0c.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of Magnetic Auricular Acupuncture on Pain during Ophthalmic Examination of the Newborn: A Multicenter, Triple-Blinded, Randomized Controlled Study","fulltext":[{"header":" Introduction","content":"\u003cp\u003eNewborn ophthalmologic examination is routinely conducted to detect retinopathy of prematurity (ROP), which is a leading cause of blindness in preterm infants [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, it is a painful procedure that involves inserting a speculum to keep the eye open, and using a bright light to examine the interior of the eye. Current forms of pain management include non-pharmacologic and pharmacologic methods. Non-pharmacological strategies such as sucrose, breast-feeding and non-nutritive sucking may mitigate the discomfort from procedures that are less painful but are usually ineffective for complex and protracted procedures like ophthalmologic examinations [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Pharmacological methods, including paracetamol, lidocaine, opioids and other sedative agents, are more effective and most frequently used for managing neonatal pain [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, many pharmacologic agents have adverse effects, including bradycardia, hypotension, respiratory depression, constipation and poor feeding. Consequently, they have to be used with care and often require intensive monitoring.\u003c/p\u003e \u003cp\u003eMagnetic auriculoacupuncture (MAA) is a new method of pain relief that is reported to be effective in infants [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The procedure is both noninvasive and simple, involving the placement of small magnets on the ear before initiating a painful procedure. In 2017, Chen et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] conducted a small pilot study in a single-blinded, randomized controlled pilot trial of 40 infants and showed that noninvasive MAA using the Battlefield Protocol [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] was safe and feasible and produced a significant, 30% reduction in pain scores compared to placebo during a heel prick procedure. In a multi-center randomized controlled trial of 100 infants at three hospitals, Gan et al [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] reported that compared to MAA infants, those in the placebo group had significantly higher Premature Infant Pain Profile (PIPP) scores [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] during and 1 h after the ROP examination. The objective of this study was to conduct a large definitive triple blinded randomized controlled trial of MAA for reducing pain in neonates undergoing ophthalmologic examination.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e \u003cb\u003eStudy Design and Population\u003c/b\u003e \u003c/p\u003e\u003cp\u003eWe conducted a multi-center, triple-blinded, randomized, placebo-controlled trial at 16 tertiary hospitals in the People’s Republic of China from April 17, 2020 to August 30, 2021.\u003c/p\u003e\u003cp\u003eParticipating hospitals included Children´s Hospital of Xinjiang Uygur Autonomous Region, Qinghai Red Cross Hospital, Shenzhen Maternity and Child Healthcare Hospital Affiliated to Southern Medical University, Inner Mongolia Maternal and Child Health Care Hospital, Children´s Hospital of Fudan University, First Affiliated Hospital of Anhui Medical University, The First Hospital of Jilin University, The First People’s Hospital of Yinchuan, Qingdao Maternal and Child Health Care Hospital, Affiliated Hospital of Qingdao University, Gansu Provincial Maternity and Child- Care Hospital, Dalian Municipal Women and Children´s Medical Center, Shanghai General Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine, Children´s Hospital of Chongqing Medical University, Children's Hospital Affiliated to Shandong University Jinan Children's Hospital, Children´s Hospital Affiliated to Zhengzhou University.\u003c/p\u003e\u003cp\u003eInfants were eligible for participation if they were born at 26 to 42 weeks gestational age (GA) and admitted to participating NICUs during the study enrollment period, and scheduled to receive an eye examination for the first time at \u0026lt; 44 weeks’ corrected GA, and whose parents provided informed consent. Exclusion criteria included infants who were critically ill or dying or who were receiving sedatives, opioids, or muscle relaxants.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOutcomes and data collection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe primary outcome was the Premature Infant Pain Profile (PIPP), which is a validated tool commonly used for measuring pain intensity in infants, and was recorded 15 minutes before, during and 15 minutes after the ophthalmologic examination procedure [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. We also recorded general behavioural state of the infant 15 minutes before the exam (e.g., sleeping, awake, agitated, or crying). Secondary outcomes included oxygen saturation, heart rate, episodes of desaturation, skin irritation, and other unanticipated adverse effects. Data were also collected on the baseline characteristics of the infant, the mother, and the delivery. These included infant sex, birth weight, GA, Apgar score at five minutes, and day of life at the time of eye exam; maternal age, primiparity, and mean parity; delivery mode; and whether the delivery was a multiple birth.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSample Size Calculation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe used the report from Chen et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] to calculate sample size. Assuming a mean (SD) PIPP score for the control group of 8 (4.5), we estimated a sample of 252 infants (126 per treatment arm) will achieve 80% power to detect a relative 20% decrease in PIPP score for the intervention group. The two-sided two sample equal-variance t-test was used for the sample size estimation at a significance level of 0.05. To account for a possible 20% missing data due to, e.g., equipment failure, 380 infants were selected through non-randomized convenience sampling method and then were divided into intervention and control groups (190 infants in each group) through simple randomization.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRandomization\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWritten informed consent was obtained from all parents. We randomized infants to intervention and control groups using a block randomization method with block size of 4 stratified by center. Dr.Su used the website of Randomization (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://randomization.com/\u003c/span\u003e\u003cspan address=\"http://randomization.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) to generate the random allocation sequence and distributed to the unblinded clinical fellows in each sub-center before the procedure. At each site, one unblinded clinical fellow was responsible for the randomization by opening a consecutive numbered, sealed, envelope containing the study group allocation, and placing the magnetic or placebo stickers on the infant. Researchers, clinicians, outcome assessors, data analysts and parents were blinded to the treatment allocation. In the event of an infant becoming ineligible after randomization, the study was postponed and recommenced when the infant became eligible, without re-randomization.\u003c/p\u003e\u003cp\u003e\u003cb\u003eProcedure\u003c/b\u003e\u003c/p\u003e\u003cp\u003eRetinal screening examinations were performed after pupillary dilation by using binocular indirect ophthalmoscopy with a lid speculum and scleral depression (as needed) to detect ROP and Congenital anomalies. Eye examinations were performed by an experienced ophthalmologist. Infants randomized to the intervention (MAA) group received noninvasive MA for at least two hours before and 30 minutes after eye exam. Magnets were placed by a clinical research fellow trained in traditional Chinese medicine (including acupuncture), on five auriculoacupuncture points on each ear according to the Battlefield Protocol [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and infants were monitored for clinical stability (heart rate, oxygen saturation, and blood pressure) for the duration of magnet placement. The magnets are commercially available (Huatuo magnetic therapy stickers) and distributed to each hospital by the center. The magnetic stickers were applied by an un-blinded clinical research fellow trained in MAA. Infants randomized to the control group were treated exactly the same as the intervention (MAA) group except that the magnets were removed from the magnet stickers to create placebo stickers. The magnetic stickers were placed on the auriculoacupuncture points in the following order: 1) Cingulate Gyrus, 2) Thalamus, 3) Omega 2, 4) Point Zero, and 5) Shenmen (HT7) (supplementary Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The magnetic stickers were checked every hour by the blinded bedside nurse until after the MAA intervention was completed and, if displaced, was replaced by the un-blinded clinical research fellow. The magnetic stickers were removed before the end of the intervention period at a parent’s request or if there are any adverse events that put the infant’s health at risk. In this study, infants were allowed to receive parent-initiated interventions for pain relief; examples include skin-to-skin contact, kangaroo care, and breastfeeding. Such interventions were carried out per unit protocols and documented.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMeasurements\u003c/b\u003e\u003c/p\u003e\u003cp\u003eInfants in both study groups were fitted with a pulse oximeter (Philips Medicin System, Germany) across the right wrist to monitor heart rate and peripheral oxygen saturation during the eye exam procedure and PIPP scoring. The PIPP score is a composite that comprises the following indicators: 1) GA (to account for physiological differences related to prematurity); 2) baseline behavioural state in the 15 seconds before the potentially painful procedure; change in 3) heart rate, and 4) oxygen saturation during the procedure (from mean value in the 15 seconds before the procedure to maximum value in the 30 seconds after the procedure); presence of a 5) brow bulge, 6) nasolabial furrow, and 7) eye squeeze during the procedure (in the 30 seconds after start of examination of the first eye)\u003c/p\u003e\u003cp\u003eThe PIPP score was measured at three time points: 15 minutes before the eye exam; during the procedure; and 15 minutes after the eye exam. To obtain the PIPP score, between 0 and 3 points are allocated for each indicator and then added together. The maximum PIPP score is 21 for preterm infants \u0026lt; 28 weeks’ GA and 18 for term infants ≥ 36 weeks’ GA, with higher scores indicating relatively more pain during the procedure, as follows: 0–6, no pain or mild pain; \u0026gt;6–12, moderate pain; \u0026gt;12, severe pain.\u003c/p\u003e\u003cp\u003e\u003cb\u003eQuality control\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe recruited 16 tertiary hospitals in China.Conducted Acunpture Workshop in 2020 at Children’s Hospital of Fudan University.Introduction of Magnetic auriculoacupuncture.Teaching how to do the Pain Score test. In addition to theoretical teaching, each fellow stuck magnetic beads on the ears of project team staff to ensure the accuracy of acupuncture points and. We played the video of venipuncture to explained each step of the PIPP score.Introduction of Acunpture Clinical Trial computer program and data Analysis.Data upload to CHNN database.Data quality contorled by coordinate centre and feedback to 16 NICUs. During the implementation of the project, we resolved any questions through the web or video conferencing.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical Analyses\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe intention-to-treat principle was applied for the data analysis. Infant characteristics were compared descriptively between the two treatment arms based on the CONSORT statement. We compared the primary outcome of PIPP score during the procedure between the two treatment arms using Wilcoxon rank sum test. The uni-variable mixed-effect linear model for repeated measures of PIPP was also conducted to examine the difference in the change of PIPP between the two treatment arms. Time, intervention group, and interaction between time and group were included in the models.\u003c/p\u003e\u003cp\u003eThe other secondary outcomes, such as heart rate, analgesia and adverse events were compared between the two treatment arms using Chi-square test or student t-test, as appropriate. The generalized linear mixed models for repeated measure of secondary outcomes were also conducted to assess the influence of acupuncture on the secondary outcome. In these models, the compound symmetry and the autoregressive covariance structures were used for the random effect (between-subject) and within-subject correlated errors, respectively. All statistical analyses were carried out in SAS version 9.4 (SAS Institute, Cary, North Carolina). A 2-sided P \u0026lt; 0.05 was considered significant. The study was approved by the institutional research ethics committee of each hospital. The trial was registered at ClinicalTrials.gov (ChiCTR1900027474),date of first registration 14/11/2019.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 408 patients were randomized from April 17, 2020 to August 30, 2021. Fourteen patients in each of the control and intervention groups did not have ophthalmologic examination because they were discharged (n = 25) or became critically ill (n = 3), leaving 190 patients in the control group and 190 in intervention group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Infant characteristics were similar in the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) except there was a higher incidence of chorioamnionitis in the intervention group.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of baseline characteristics between Acupuncture and Placebo group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAcupuncture\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStatistics\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePvalue\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e204\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e204\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e408\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfant Characteristics\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational Age, wk, median (IQR)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.86 ( 30.21, 37.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.00 ( 30.71, 37.93)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33.00 ( 30.50, 37.57)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight, g, mean (std)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,085.49 ( 893.13)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2,175.75 ( 920.59)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2,130.62 ( 906.97)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1.005\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118/ 204 ( 57.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e115/ 204 ( 56.4)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e233/ 408 ( 57.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.764\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSGA,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23/ 204 ( 11.3)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16/ 204 ( 7.8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39/ 408 ( 9.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.389\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.239\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInborn,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136/ 204 ( 66.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e138/ 204 ( 67.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e274/ 408 ( 67.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay of Life at enrollment,days, median (IQR)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.00 ( 7.00, 31.50)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.00 ( 5.50, 32.50)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23.00 ( 7.00, 32.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.141\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.888\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwin, n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48/ 204 ( 23.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45/ 204 ( 22.1)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e93/ 408 ( 22.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 min Apgar less than 7,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33/ 195 ( 16.9 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29/ 193 ( 15.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e62/ 388 ( 16.0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 min Apgar less than 7,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/ 195 ( 6.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8/ 189 ( 4.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21/ 384 ( 5.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.294\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal Characteristics\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarriage Status,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e203/ 204 ( 99.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e201/ 204 ( 98.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e404/ 408 ( 99.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81/ 204 ( 39.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85/ 204 ( 41.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e166/ 408 ( 40.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.163\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssitant pregnancy,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37/ 203 ( 18.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38/ 204 ( 18.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e75/ 407 ( 18.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-section,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126/ 204 ( 61.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e138/ 204 ( 67.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e264/ 408 ( 64.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.545\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.214\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterine contraction,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84/ 133 ( 63.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72/ 135 ( 53.3 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e156/ 268 ( 58.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.658\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimigravida,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104/ 204 ( 51.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e112/ 204 ( 54.9 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e216/ 408 ( 52.9 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eROM over 24h,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/ 164 ( 17.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36/ 169 ( 21.3 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64/ 333 ( 19.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.959\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal Fever,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/ 204 ( 2.9 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3/ 204 ( 1.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9/ 408 ( 2.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.023\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.312\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChorioamnionitis,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/ 186 ( 10.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34/ 188 ( 18.1)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54/ 374 ( 14.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.069\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal Smoking,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/ 198 ( 0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/ 201 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1/ 399 ( 0.3 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.988\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMgSO4 usage,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58/ 187 ( 31.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61/ 188 ( 32.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e119/ 375 ( 31.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.766\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression during pregnancy,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/ 184 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/ 186 ( 0.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3/ 370 ( 0.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.347\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.556\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal Outcome\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRDS,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92/ 201 ( 45.8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86/ 204 ( 42.2)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e178/ 405 ( 44.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVH Grade ≥ 3,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/ 204 ( 1.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2/ 204 ( 1.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4/ 408 ( 1.0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eROP Stage ≥ 3,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/ 204 ( 2.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6/ 204 ( 2.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11/ 408 ( 2.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate \u0026amp; severe BPD,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/ 204 ( 5.9 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15/ 204 ( 7.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27/ 408 ( 6.6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.357\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate \u0026amp; severe HIE,n/N (%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/ 204 ( 1.0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1/ 204 ( 0.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3/ 408 ( 0.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e: \u003cb\u003eThe flow chart of the study\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cb\u003eComparison of baseline characteristics between Acupuncture and Placebo group\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere was no difference in mean PIPP scores between the intervention and control groups, before and after eye exam (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, mean PIPP scores during eye exam were significantly lower in the intervention group compared to the control group (median (IQR): 10.00 (5.00,13.00) v 12.00 (7.00,14.00), p = 0.038) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePIPP scores before, during and after ophthalmologic examination procedure\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePlacebo\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAcupuncture\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePIPP, median (IQR)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.00 ( 2.00, 4.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.00 ( 1.00, 4.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.00 ( 7.00, 14.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.00 ( 5.00, 13.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.00 ( 2.00, 4.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.00 ( 2.00, 4.00)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. \u003cb\u003ePIPP scores before, during and after ophthalmologic examination procedure\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e: \u003cb\u003eMean PIPP scores before, during and after procedure\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere was no significant difference in heart rate, oxygen saturation, or episodes of desaturation between the intervention and control groups before, during and after eye exam (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Eleven infants in the control group and 9 infants in intervention group (p = 0.15) experienced skin irritation on the ear, and there were no other anticipated adverse effects. There were no differences in other pain management use between the groups.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSecondary outcomes of magnetic auricular acupuncture on pain during ophthalmic examination\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSaO2 \u0026lt; 90%,n/N (%)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/ 190 ( 3.2)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12/ 190 ( 6.3)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18/ 380 ( 4.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67/ 190 ( 35.3)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54/ 190 ( 28.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121/ 380 ( 31.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/ 190 ( 2.6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/ 190 ( 2.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9/ 380 ( 2.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.736\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeart Rate, beats per min, mean (std)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144.47 ( 14.76)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142.98 ( 13.94)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e143.72 ( 14.36)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.312\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e171.14 ( 22.64)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169.11 ( 21.40)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e170.13 ( 22.03)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144.39 ( 12.44)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142.47 ( 13.56)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e143.43 ( 13.03)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdverse Effect,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/ 190 ( 0.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3/ 380 ( 0.8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26/ 190 ( 13.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17/ 190 ( 8.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43/ 380 ( 11.3 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/ 190 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/ 190 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/ 380 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSkin irritation,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/ 190 (0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/ 380 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/ 190 ( 4.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8/ 190 ( 4.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16/ 380 ( 4.2)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/ 190 ( 0.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/ 190 ( 0.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/ 380 ( 0.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDesaturation,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/ 190 (0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/ 190 (0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/ 380 (0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/ 190 ( 9.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/ 190 ( 4.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27/ 380 ( 7.1)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/ 190 (0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/ 190 (0 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/ 380 (0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnalgesia,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/ 190 ( 6.3 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11/ 190 ( 5.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23/ 380 ( 6.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/ 190 ( 4.7 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12/ 190 ( 6.3 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21/ 380 ( 5.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.501\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22/ 190 ( 11.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20/ 190 ( 10.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42/ 380 ( 11.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.744\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBreastfeeding,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/ 190 ( 2.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/ 190 ( 3.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10/ 380 ( 2.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/ 190 ( 2.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/ 380 ( 1.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/ 190 ( 8.4)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16/ 190 ( 8.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32/ 380 ( 8.4 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePacificer,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/ 190 ( 2.6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/ 190 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/ 380 ( 1.6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/ 190 ( 3.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/ 190 ( 3.2 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12/ 380 ( 3.2)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/ 190 ( 2.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/ 380 ( 1.6 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKangaroo care,n/N (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/ 190 ( 1.6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/ 190 ( 2.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7/ 380 ( 1.8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuring procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/ 190 ( 0.5 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3/ 380 ( 0.8 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter procedure\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/ 190 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4/ 380 ( 1.1 )\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. \u003cb\u003eSecondary outcomes of magnetic auricular acupuncture on pain during ophthalmic examination\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMagnets were placed on five auriculoacupuncture points on each ear according to the Battlefield Protocol.The five auricular points are stimulated sequentially in the following order on each ear: 1- Cingulate Gyrus, 2- Thalamus, 3- Omega 2, 4- Point Zero, 5- Shenmen (HT7). Using cotton plug preventing magnetic fall into external auditory canal\u003c/p\u003e\u003cp\u003e \u003cb\u003eSupplementary Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e. Battlefield acupuncture protocol.\u003c/b\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our best knowledge, this is the largest definitive trial of magnetic auricular acupuncture (MAA) pain management during ophthalmologic examination in infants, and confirms the results of previous smaller trials by Chen et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and Gan et al [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Our results show that MAA results in a 20% reduction in PIPP scores, which is consistent with the 30% reduction reported by Chen et al [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. There were no ill effects except for mild transient skin irritation in 4.2% (n = 16/380) of infants, who were equally distributed in the intervention and control groups. The MAA magnet stickers were cheap, easily placed by trained personnel and did not interfere with routine newborn care. It is possible that MAA may offer an alternate to current non-pharmacologic and pharmacologic interventions to alleviate neonatal pain since they remain inadequate and are inconsistently applied in many countries, including China.\u003c/p\u003e\u003cp\u003ePain has immediate physiologic impacts on the infant, including cardiovascular changes, behavioral changes, feeding disruption, disturbed sleep, and increased energy expenditure, and may result in prolonged need for intensive care [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Untreated pain experiences during hospitalization early in life may have long-term consequences, including increased pain sensitivity, decreased immune system functioning, increased avoidance behavior, and social hypervigilance [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Early life painful experiences in the neonatal intensive care unit (NICU) may also influence the developing gut microbiome [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and impact development of the brain structure and function on the cortical and subcortical levels [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e–\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Both frontal and parietal cortex volume and thickness have been found to decrease and lead to neurodevelopmental impairment [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, pain control is an important part of newborn care.\u003c/p\u003e\u003cp\u003eNon-pharmacologic methods like sucrose, breast-feeding and non-nutritive sucking are commonly used but are only marginally effective. In a randomized controlled trial conducted in four groups to evaluate the use of oral sucrose and or pacifier for reducing pain responses during neonatal eye examinations using the premature infant pain profile (PIPP) scoring system, Boyle et al [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] reported that the mean (SD) PIPP scores were 15.3 (1.9), 14.3 (1.6), 12.3 (2.9), and 12.1 (3.4) for sterile water, sucrose, pacifier, and sucrose combined pacifier groups respectively, indicating that these methods reduced pain only marginally. It is also unclear whether sucrose really produces analgesia or only modifies pain-associated expressions and behaviours [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and its long-term effects are poorly understood. Similarly, Nayak et al’s study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] of expressed breast milk, 10% dextrose or sterile water administered orally before ROP screening in preterm neonates similarly did not significantly alleviate pain during the procedure. The frequent use of pharmacologic agents like sedatives (e.g. diazepam) and opioids (e.g. morphine, fentanyl) may have negative consequences for neurodevelopment [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A clear need exists for alternative pain management techniques that are safe and effective for infants.\u003c/p\u003e\u003cp\u003eAcupuncture is a form of non-pharmacological pain management that has been practiced for over 2000 years by Traditional Chinese Medicine (TCM) practitioners and has recently been applied to neonates [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It involves the insertion of very thin needles through the skin at strategic points on the body, and is based on the idea of energy (“Chi”) circulating through the body through meridian pathways. Although the mechanism of action is unknown, some speculate that it works by stimulation of the endorphin system [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition to needle acupuncture, there are also noninvasive methods such as magnetic auricular acupuncture (MAA) that involve applying small magnets to strategic points on the meridians. MAA is an attractive method for pain management in neonates who have thin sensitive skin, as it is non-invasive, affordable, portable, can easily be administered in a busy NICU setting [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAssessing pain is difficult and becomes even more challenging when the subjects are very young or preverbal. Because of this difficulty, and because the pharmacological forms of analgesia often used in the NICU have potentially detrimental side effects, infant pain is often neglected or poorly managed. Strategies for achieving pain management are variable, ranging from the absolute absence of pain assessment or management to protocols wherein doses, regimens, and routes of administration are not standardized. A survey of Jiangsu Province Medical Quality Control Centre NICUs found that medical and nursing staff answered basic knowledge questions about neonatal pain correctly only 38% and 39% respectively [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Wang et al [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported that infants born at 34–39 weeks GA experienced an average of 66.5 painful procedures during their hospital stay, and the pain score was highest (7.0 points) for procedures involving ophthalmic examination and percutaneous central catheter insertion. It is therefore essential for NICU staff to understand and implement both nonpharmacological and pharmacological strategies for neonatal pain relief.\u003c/p\u003e\u003cp\u003e \u003cb\u003eLimitations\u003c/b\u003e \u003c/p\u003e\u003cp\u003eThe study was disrupted by the Covid pandemic, which led to intermittent suspension of patient recruitment, prevention of hospital visits by parents, hospital and bed closures, staff displacement and other inconveniences. This led to repeated study starts and stops at different hospitals, the study period was prolonged and we had to abandon sequential patient recruitment in favor of convenient subject sampling. The mean GA in our study was 32.8 weeks in the control group and 33 weeks in the MAA group, with no involvement of extremely preterm infants. We did not measure the impact of acupuncture on long term outcomes, including neurodevelopment and future studies should take these knowledge gaps into account.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received ethical approval from the ethics committee of\u0026nbsp;People\u0026rsquo;s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China(KY2019082101)，the\u0026nbsp;16\u0026nbsp;recruiting hospitals\u0026nbsp;obtained\u0026nbsp;approval from their hospitals.\u0026nbsp;Informed consent was obtained from all parents, with the same informed consent form being used at all centres. The study was registered in Chinese Clinical Trial Registry (registration number, ChiCTR1900027474 ), \u0026nbsp;date of \u0026nbsp;registration\u0026nbsp;14/11/2019. The\u0026nbsp;trial\u0026nbsp;of\u0026nbsp;MAA\u0026nbsp;was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all parents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr Lee is supported by a grant from the Canadian Institutes of Health Research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDrs \u0026nbsp;Li, Tuerxun, \u0026nbsp;and Shoo K. Lee conceptualized and designed \u0026nbsp;the trial, and contributed to interpreting the results; Drs Tuerxun and Yajie Su contributed to \u0026nbsp; acquisition of data, coordinated and supervised data collection, \u0026nbsp;Drs Li, Shoo K. Lee and Yancheng Wang contributed to the data analysis and interpreted the results; \u0026nbsp;Drs Li, Shoo K. Lee, Laishuan Wang and Tuerxun contributed to drafting of the manuscript. All authors contributed to acquisition of data and critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the infants, parents, nurses, neonatologists, and other clinical staff who participated in this trial. We also thank all the recruiting hospitals involved in the study. Their help and support were invaluable since they contributed significantly to the trial\u0026rsquo;s success. We also thank\u0026nbsp;Chinese Neonatal Network for\u0026nbsp;technical\u0026nbsp;and\u0026nbsp;\u0026nbsp;material support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZeraati H, Shahinfar J, Vashani HB, Reyhani T. 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Magnetic Non-invasive Auricular Acupuncture During Eye-Exam for Retinopathy of Prematurity in Preterm Infants: A Multicentre Randomized Controlled Trial. Front. Pediatr.23 December 2020://DOI.org/10.3389.\u003c/li\u003e\n\u003cli\u003eStevens B, Johnston C, Petryshen P, Taddio A. Premature Infant Pain Profile: development and initial validation. Clin J Pain. 1996;12(1):13-22.\u003c/li\u003e\n\u003cli\u003eAbdulkader HM, Freer Y, Garry EM, Fleetwood-Walker SM, McIntosh N. Prematurity and neonatal noxious events exert lasting effects on infant pain behaviour. Early Hum Dev 2008;84:351\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eGiboney Page, G. Are there long-term consequences of pain in newborn or very young Infants? J Perinatal Edu. 2004;13(3):10-18.\u003c/li\u003e\n\u003cli\u003eD\u0026rsquo;Agata AL, Wu J, Welandawe MKV, Dutra SVO, Kane B, Groer MW. Effects of Early Life NICU Stress on the Developing Gut Microbiome. Dev Psychobiol. 2019 July ; 61(5): 650\u0026ndash;660.\u003c/li\u003e\n\u003cli\u003eBajic D, Commons KG, Soriano SG. Morphine-enhanced apoptosis in selective brain regions of neonatal rats. Int J Dev Neorosci. 2013;31:258-266.\u003c/li\u003e\n\u003cli\u003eDuerden EG, Grunau RE, Guo T, Foong J, Pearson A, Au-Young S, et al. Early procedural pain is associated with regionally-specific alterations in thalamic development in preterm neonates. J Neurosci 2018;38:878\u0026ndash;86.\u003c/li\u003e\n\u003cli\u003eRanger M, Chau CMY, Garg A, Woodward TS, Beg MF, Bjornson B, et al. Neonatal pain related stress predicts cortical thickness at age 7 Years in children born very preterm. PLoS One 2013;8:.\u003c/li\u003e\n\u003cli\u003eSmith GC, Gutovich J, Smyser C, Pineda R, Newnham C, Tjoeng TH, et al. Neonatal intensive care unit stress is associated with brain development in preterm infants. Ann Neurol 2011;70:541\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eNayak R, Nagaraj KN, Gururaj G. Prevention of Pain During Screening for Retinopathy of Prematurity: A Randomized Control Trial Comparing Breast Milk, 10% Dextrose and Sterile Water. Indian J Pediatr. 2020; 87(5): 353\u0026ndash;358. DOI: 10.1007/s12098-020-03182-6.\u003c/li\u003e\n\u003cli\u003eLee KA, Ganta N, Horton JR, Chai E. Evidence for neurotoxicity due to morphine or hydromorphone use in renal impairment: a systematic review. J Palliat Med. (2016) 19:1179\u0026ndash;87. DOI: 10.1089/jpm.2016.0101.\u003c/li\u003e\n\u003cli\u003eJiangsu Province Medical Quality Control Centre of Neonatal Department. An investigation on the cognition of neonatal pain assessment and analgesia management among medical staff in the neonatal intensive care unit. Chinese Journal of Contemporary Pediatrics 2021,23(12):1271-1275. DOI: 10.7499/j.issn.1008-8830.2107116.\u003c/li\u003e\n\u003cli\u003eWang Yajing. The status and influencing factors of operant pain in neonatal intensive care unit. Pediatr Nursing 2019 https://DOI.org/10.1111/jspn.12281.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Magnetic Auricular Acupuncture, Neonatal pain, Ophthalmic Examination, PIPP scores","lastPublishedDoi":"10.21203/rs.3.rs-4488158/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4488158/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eNewborn ophthalmologicexamination is a painful procedure. Untreated pain experiences in infants have both short-term and long-term consequences, and pain control is essential. Unfortunately, non-pharmacological pain strategies are usually ineffective for complex and protracted procedures, whereas many pharmacologic agents have adverse effects. Magnetic auricular acupuncture (MAA) is a new method of pain relief that is potentially safe and effective. The objective of this study was to conduct a large definitive triple blinded randomized controlled trial of MAA for reducing pain in neonates undergoing ophthalmologic examination. The trial was registered at ClinicalTrials.gov (ChiCTR1900027474). The registration was completed on November 14, 2019.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This was a multi-centerrandomized controlled trial conducted at 16 tertiary hospitals in the People’s Republic of China. Infants were eligible for participation if they were born at 26 to 42 weeks gestational age (GA) and admitted to participating NICUs during the study enrollment period, and scheduled to receive an eye examination for the first time at \u0026lt;44 weeks’ corrected GA. Written informed consent was obtained from parents. Infants who were critically ill, dying or receiving sedatives were excluded. Infants randomized to the intervention (MAA) group receivedmagnetic stickers applied prior to the ophthalmologic procedure. Control group infants received placebo stickers with the magnets removed. We compared the primary outcome of Premature Infant Pain Profile (PIPP) score during the procedure between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u0026nbsp;\u003c/strong\u003eA total of 408 patients were randomized, but 14 patients in each of the placebo and intervention groups did not receive ophthalmologic examination; leaving 190 patients in control group and 190 in intervention group. Infant characteristics were similar in the two groups,mean PIPP scores during eye exam were significantly lower in the intervention group compared to the control group (median (IQR): 10.00 (5.00,13.00) v 12.00 (7.00,14.00), p = 0.038).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions：\u003c/strong\u003eMAA may offer an alternate to current non-pharmacologic and pharmacologic interventions to alleviate neonatal pain. Future studies should assess the long term outcomes.\u003c/p\u003e","manuscriptTitle":"Effect of Magnetic Auricular Acupuncture on Pain during Ophthalmic Examination of the Newborn: A Multicenter, Triple-Blinded, Randomized Controlled Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-15 19:15:30","doi":"10.21203/rs.3.rs-4488158/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-17T04:27:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-16T12:31:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-16T12:30:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-05-28T05:12:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"105f7262-16a9-4d21-8aa2-296aef881a2e","owner":[],"postedDate":"July 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:07:55+00:00","versionOfRecord":{"articleIdentity":"rs-4488158","link":"https://doi.org/10.1186/s12887-025-06126-1","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-10-03 15:58:13","publishedOnDateReadable":"October 3rd, 2025"},"versionCreatedAt":"2024-07-15 19:15:30","video":"","vorDoi":"10.1186/s12887-025-06126-1","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06126-1","workflowStages":[]},"version":"v1","identity":"rs-4488158","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4488158","identity":"rs-4488158","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}