Effect of Acupoint Hot Compress on Postpartum Urinary Retention After Vaginal Delivery

This randomized clinical trial evaluates urinary retention, uterine contraction pain, depressive symptoms, and lactation after acupoint hot compress treatment in women during their early postpartum period.

The objective of this study was to assess the effects of acupoint hot compress during early 365 puerperium on parturients after a vaginal delivery. 366

Background 367
Early puerperium is the period of adjustment after delivery, which extends until the first week 368 postpartum. 1-3 It is recommended that mothers and newborns should receive care within 24 hours after 369 birth as recommended by the World Health Organization guidelines for postnatal care, and this includes 370 the assessment of micturition, urinary incontinence and bowel function, healing of any perineal wounds, 371 fatigue, pain, uterine tenderness and lochia, and improving the breastfeeding progress and emotional 372 well-being. 4 These issues can interfere with a woman's ability to care for herself and her infant. 5,6 373 Moreover, maternal self-care needs, already in the first few days after delivery, go beyond the mother's 374 physical health as it extends to the mother's emotional well-being as well. 7 375 Hot compresses have proved to be an effective complementary treatment for myofascial pain 376 syndrome in the upper trapezius muscle, 8 and they have exhibited an extraordinary capability for the 377 pressure pain threshold and in improving the quality of life. 9 Warm compress bistage intervention was 378 found to significantly reduce the intensity of pain the day after delivery. 10 Acupoint hot compress, with a 379 combination of acupoints and natural physical agent heat, is more acceptable, both physically and 380 mentally, for puerperal patients and their families, due to its noninvasive feature. However, the effects of 381 acupoint hot compress for patients during the early puerperium remain uncertain due to a lack of 382 evidence-based support from clinical trials. 383

Objectives 385
The trial is designed to evaluate whether acupoint hot compress involving the abdominal, 386 lumbosacral and plantar regions could reduce the incidence of postpartum urinary retention, relieve 387 postpartum uterine contraction pain, prevent emotional disorders, and promote lactation. 388 389

Trial registration 390
The final protocol version is 2.

Trial design 398
The study is a prospective, multi-center, and randomized controlled clinical trial, which will be 399 conducted in China. All enrolled subjects will be comprehensively briefed on the study, including the 400 purpose, procedure, and possible risks of the study. Informed consent will be obtained from all 401 participants before the start of this study. The demographic data, information about pregnancy, delivery, 402 and newborns will be recorded as baseline data. When the protocol need to be modified, the 403 implementation will be started only after the corresponding revised parts approved by the ethics

Recruitment 420
The study will be conducted in 12 hospitals This study will use a superiority design. According to the pilot study, the incidence rate of urinary 463 retention was 7.7% in the intervention group and 25.7% in the control group. Assuming a 1 : 1 ratio of 464 intervention to control group and using a one-sided test, a significance level (α) of 0.025 and a power (1-β) 465 of 80% and a possible drop-out rate of 20%, the estimated sample size is 600 cases in each group with 50 466 cases at each center in each group. Intervention and control groups would require a total sample size of 467 1200 cases. 468 469

Randomization and blinding 470
Eligible subjects will be randomly assigned to the intervention group or control group in a ratio of 471 1:1. The randomization number sequence will be generated with R software by an independent 472 statistician. Randomization number sequence will be stored by a non-involved investigator. The design is 473 open label, but the outcome assessors and statisticians who are blinded to group allocation will be 474 responsible for collecting and analyzing the data, respectively. 475  The time point of the first urination after delivery and whether an indwelling catheter was used 545 within 72 hours after delivery will be recorded. In the present trial, postpartum urinary retention is 546 defined as the first urination occurring more than 6.5 hours after delivery and/or if an indwelling catheter 547 is used within 72 hours after delivery. 4,14-16 548 549

Secondary outcomes 550
Postpartum uterine contraction pain: The visual analogue scale (VAS) will be used to evaluate the 551 postpartum uterine contraction pain intensity: Using a horizontal ruler of 100 mm, "0" representing no 552 pain and "100" representing unbearable pain. The pain VAS intensity will be respectively measured at 6 553 ± 0.5 hours, 28 ± 0.5 hours, 52 ± 0.5 hours, and 76 ± 0.5 hours after delivery. 17 554 Emotion symptoms: The Edinburgh Postnatal Depression Scale (EPDS) will be used for screening 555 the depressive symptoms at 76 ± 0.5 hours after delivery. It contains 10-item: pessimism, lack of interest, 556 self-blame, worry, fear, impaired ability, sleep disorder, sadness, tearfulness, self-injury/suicidal ideation, 557 each of which is scored from 0 to 3. 6 558 Lactation: The lactation initiation time will be recorded, and the breastfeeding milk volume, feeding 559 mood and times, and the newborn weight will be measured at 28±0.5, 52±0.5, and 76±0.5 hours after 560 delivery, respectively. The breastfeeding milk volume is measured as "-" to "++++": no milk outflow 561 during finger extrusion(-); milk occasionally flows out during finger extrusion, which cannot meet the 562 needs of the infants (+); milk flows out slowly when squeezed by fingers but does meet the needs of 563 infants (+ +); milk continuously flows out during finger extrusion, which can meet the needs of infants (+ 564 + +); there is milk flowing out in a jet shape when the nipple is squeezed by the fingers, which can meet 565 the needs of infants (+ + + + ). 18,19 566 567

Safety Evaluation 568
The medical device for hot compress used in the present study is licensed by Medical Products 569 Administration (Jiangxi Province, China) with a Licensed Number 20192090292. No adverse events 570 (AEs) have been reported. In the present study, the safety evaluation will be comprehensively conducted 571 and followed. In the study, the participants with sensory disorders have been excluded. Prior to obtaining 572 consent from the participants, the potential AEs have been explained to the participants in detail. AEs 573 will be monitored and recorded in detail throughout the whole study period. 574 575

Notification Page 577
Dear: 578 You will be invited to participate in a prospective, multi-center, and randomized controlled clinical 579 trial on the effects of acupoint hot compress on early puerperal rehabilitation of parturients with vaginal 580 delivery. Before you decide whether to participate in this study, please read the following contents as 581 carefully as possible. It can help you understand why it is conducted, the procedures and duration of the 582 study, benefits, risks and discomforts. You can feel free to ask the investigator for explanations to help 583 you make your decision. 584

I. Study Background 585
Puerperal diseases negatively affect the physical and mental health of parturients and the growth and 586 development of infants, and even the development of society. In face of a large reproductive-age 587 population, it is particularly important to evaluate and prevent early puerperium urinary retention, 588 uterine contraction pain, emotional and lactation disorders. To access the effects of early puerperal acupoint hot compress in reducing the incidence of postpartum 606 urinary retention, relieving postpartum uterine pain, promoting lactation, and preventing mood disorders, 607 which could provide a scientific basis for the application of non-drug therapy in puerperal rehabilitation. 608

III. Study methods and contents 609
We will give a random number to each participant and establish a file. Based on the randomization 610 number, you will be randomized to one of the two groups. After routine postpartum care, the intervention 611 group will be given acupoint hot compress at a constant temperature of 45±2℃ within 30 minutes after 612 vaginal delivery, 24 hours after delivery, and 48 hours after delivery, with 4 hours each time, and the 613 control group will be given routine postpartum care only. 614 Acupoint hot compress will be applied with a licensed medical device Hu-Chao-Nuan-Gong-Bao with 615 produced by Jiangxi Shenghe Industrial Development Co., Ltd., Nanchang, China. 616 We will assess the postpartum urinary retention at 6±0.5 hours after delivery, postpartum uterine 617 contraction pain at 6±0.5 hours, 28±0.5 hours, 52±0.5 hours, and 76±0.5 hours after delivery, lactation at 618 28±0.5 hours, 52±0.5 hours, and 76±0.5 hours after delivery, and postpartum depressive symptoms at 76 619 ± 0.5 hours after delivery. will fully explain and give effective guidance to you. During the study, we will strictly control the 653 inclusion and exclusion criteria. 654 Benefits: Those randomized to the intervention group during the study may intervene to reduce the 655 incidence of postpartum urinary retention, relieve postpartum uterine pain, promote lactation, prevent 656 mood disorders, which has positive effects on puerperal health. Although there is evidence to indicate a 657 satisfactory response, this does not guarantee that it will work for you. During the study, we will inform 658 you in a timely manner if we learn of any information that may affect your continued participation in the 659 study. 660

VIII. Costs and Compensation 661
Cost: The cost of acupoint hot compress in this study will be covered by the investigator, and the cost of 662 routine diagnosis and other treatment items will be self-paid. We will make effort to prevent and treat 663 possible adverse events due to this study. If an adverse events occurs, whether or not related to this study, 664 you will receive timely treatment. If confirmed that it is related to this study, we will provide the cost of 665 diagnosis, treatment and the corresponding compensation for the study-related damage in accordance 666 with the provisions of relevant laws or guidelines in China. 667 Compensation: After all the follow-up assessments are completed, we will pay RMB 100 Yuan per 668 subject. 669

IX. Confidentiality 670
Records about your identity are kept confidential and your name will not appear on case report 671 forms(CRFs), any relevant study reports and public publications. Your medical data will be used for 672 scientific research only and will not be used for any commercial purposes. The investigator, sponsor 673 representative, monitors, ethics committee and regulatory authorities will be allowed access to your 674 medical records. We will make effort to protect the privacy of your personal medical data to the extent 675 permitted by law. 676 You have the right to learn about yourself at any time during the study. 677

X. Voluntary principle 678
Whether to participate in the study depends entirely on your wishes. You may refuse to participate in the 679 study or withdraw from the study at any time during the study. This will not affect your medical treatment 680 or other benefits. 681 The doctor or investigator may discontinue your participation in the study at any  After fully understanding all the information for subjects and the risks and benefits of participating in the 718 trial, I have sufficient time to think about it and I will voluntarily participate in the trial, fully cooperate 719 with the investigators, truthfully and objectively provide the investigators with the health status and 720 related conditions before participating in the study. 721 I understand that I can consult investigator for more information at any time, and I can choose not to 722 participate in this study, or quit at any time after informing the researcher without any discrimination or 723 reprisals, and my medical treatment and rights will not be affected. 724 I am also aware that if I withdraw from the study halfway, especially due to the use of the medical device. 725 To inform the investigator of the changes of my conditions and complete the corresponding physical 726 examinations and chemical examinations, will be very beneficial to the whole study. If I need to take any 727 other medication due to changes of my conditions, I will ask the investigator for advice in advance or tell 728 the investigator truthfully afterwards. In previous studies and clinical practice, acupoint hot compress used by Hu-Chao-Nuan-Gong-Bao 751 has not been reported to have any adverse event. 752 If the subject experiences any adverse event, she can call the researcher at any time, and the 753 researcher will fully explain and provide effective guidance. If an adverse event occurs, no matter it is 754 related to this study or not, the subject will be treated in time. After confirmation by relevant experts from 755 medical institutions and centers, the treatment costs will be covered by the clinical study sponsor and 756 appropriate economic compensation will be given according to relevant national regulations. 757 758

Benefits 759
During the study, allocation to acupoint hot compress intervention group may reduce the incidence 760 of postpartum urinary retention, relieve postpartum uterine contraction pain, prevent emotional disorders, 761 and promote lactation, which has a positive effect on puerperal health. Although there are evidences to 762 suggest a satisfactory response, this does not guarantee a positive response for each subject. The 763 intervention used in this study is not the only choice. If it is ineffective for the subject's condition, the 764 subject can ask the physician for alternative treatment. During the study, if we learn of any information 765 that may affect the continued participation of parturients in the study, the subject will be informed in 766 time. 767 768 6. Data Management 769 All the investigators will receive standard training and operate strictly according to the standard 770 procedure. Double data entry will be applied to ensure the accuracy. A data monitoring committee will be 771 set up before the first enrollment of participants. The original data will be collected and recorded in case 772 report forms (CRFs). Each participant and the investigator will sign and record the date on CRFs, which 773 will be maintained in a secure location. All the data and CRFs during the study are available from the 774 corresponding author on reasonable requests. After publication of the study, all the relevant data will be 775 stored for 3 years in Women's Hospital, School of Medicine, Zhejiang University. 776 777

Statistical analysis 778
The following is an overview of the statistical considerations. Details of the pre-specified 779 statistical analyses can be found in Statistical Analysis Plan (SAP). 780 Statistical analysis will be performed by independent analysts by using R (version 4.1.0; R 781 Development Core Team) software. All the analyses will be based on an intention-to-treat principle. 782 Continuous data will be represented by the average, standard deviation, median, minimum and maximum 783 value; categorical data will be represented by the number and percentages. Continuous data will be 784 analyzed using the t test or one-way ANOVA; Wilcoxon-Mann-Whitney test will be used when necessary. 785 Categorical data will be analyzed using the chisquare test or Fisher's exact test. The logistic regression 786 model or linear regression model and linear mixed model will also be used to find the relationship 787 between independent variables. The subgroup relative risk (RR) and the corresponding 95% confidence 788 intervals (CIs) are calculated together with interaction P values. P < 0.05 will be considered statistically 789 significant. 790 791

Privacy 792
If the subject decides to participate in this study, the data of the subject recorded throughout the 793 study are only used for scientific research purpose and not for any news or commercial ones. The 794 personal data of the subjects involved will be kept strictly confidential. When the study are published, 795 none of the personal privacy such as the name and contact information of the subjects will be identified. 796 After the study is published, all the study materials will be preserved in Women's Hospital School of 797 Medicine, Zhejiang University for verification of study implementation required by national regulatory 798 authorities, scientific research management authorities and Ethics Committee. 799 800

Funding 801
This study is supported by Association for Maternal and Child Health, Zhejiang Province, China 802