CenteringPregnancy Oral Health Promotion (CPOP) Clinical Trial
Phase: NA
Conditions: Oral Health
Sponsor: University of California, San Francisco

CenteringPregnancy Oral Health Promotion (CPOP)
Version 2.03
Protocol  18-029E
October 15, 2020
CenteringPregnancy Oral Health Promotion 
(CPOP) Clinical Trial
NIDCR Protocol Number: 18-029-E 
NIDCR Grant Number: 1 U01 DE027340-01
Principal Investigators: Lisa Berens, DDS, MPH                                   
                                      Sally Adams, RN, PhD
NIDCR Program Scientist:  Darien Weatherspoon, DDS, MPH
NIDCR Program Official: Dena Fischer, DDS, MDS, MS
NIDCR Medical Monitor: Kevin McBryde, MD
Draft or Version Number:  2.03
October 15, 2020

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Version 2.03
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Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103
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STATEMENT OF COMPLIANCE
The study will be conducted in accordance with the International Council for 
Harmonisation guidelines for Good Clinical Practice (ICH E6), the Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), and the NIDCR 
Clinical Terms of Award. All personnel involved in the conduct of this study have 
completed human subjects protection training.

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SIGNATURE PAGE
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines.
Principal Investigator or Clinical Site Investigator:
Signed:
Date:
October 14, 
2020
Name: Lisa Berens
Title:  Associate Clinical Professor
Signed:
Date:
October 14, 
2020
Name: Sally Adams
Title:  Full Specialist 6

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TABLE OF CONTENTS
PAGE
STATEMENT OF COMPLIANCE ...................................................................................................I
SIGNATURE PAGE.......................................................................................................................II
TABLE OF CONTENTS ...............................................................................................................III
LIST OF ABBREVIATIONS..........................................................................................................VI
PROTOCOL SUMMARY............................................................................................................VIII
1.
KEY ROLES AND CONTACT INFORMATION ..................................................................12
2.
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE .......14
2.1 
Background Information..........................................................................................14
2.2 
Rationale.................................................................................................................15
2.3 
Description of the CPOP intervention .....................................................................16
2.4 
Potential Risks and Benefits ...................................................................................17
2.4.1 Potential Risks ............................................................................................17
2.4.2 Potential Benefits ........................................................................................17
3.
OBJECTIVES .....................................................................................................................18
3.1
Study Objectives.....................................................................................................18
3.1.1
Primary Objective 1.....................................................................................18
3.1.2
Primary Objective 2.....................................................................................18
3.1.3
Secondary Objective 1................................................................................18
3.1.4
Secondary Objective 2................................................................................18
3.1.5
Secondary Objective 3................................................................................19
3.2 
Study Outcome Measures ......................................................................................19
3.2.1 Primary Outcomes ......................................................................................19
3.2.2 Secondary Outcomes..................................................................................19
4.
STUDY DESIGN.................................................................................................................19
5.
STUDY ENROLLMENT AND WITHDRAWAL....................................................................22
5.1 
Subject Inclusion Criteria ........................................................................................22
5.2 
Subject Exclusion Criteria.......................................................................................23
5.3 
Strategies for Recruitment and Retention...............................................................23
5.4 
Treatment Assignment Procedures ........................................................................24
5.4.1 Randomization Procedures.........................................................................24
5.4.2 Masking Procedures ...................................................................................24
5.5 
Subject Withdrawal .................................................................................................25
5.5.1 Reasons for Withdrawal..............................................................................25
5.5.2 Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention .................................................................................................25
5.6 
Premature Termination or Suspension of Study.....................................................25
6.
STUDY INTERVENTION....................................................................................................26
6.1 
Study Behavioral or Social Intervention(s) Description...........................................26
6.2 
Administration of Intervention .................................................................................27
6.3 
Procedures for Training Interventionists and Monitoring Intervention Fidelity ........27

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6.4 
Assessment of Subject Compliance with Study Intervention..................................28
7.
STUDY SCHEDULE...........................................................................................................28
7.1 
Screening and Recruitment ....................................................................................28
7.2 
Baseline Data Collection (Visit 1, Day 0) ................................................................28
7.3 
Intermediate Visits ..................................................................................................29
7.3.1 Visit 2 (Day 14 ± 14) Maternal Intervention Administration............................29
7.3.2 Visit 3 (Day 84+/- 15): Post-Maternal & Pre-Infant Intervention Data 
Collection ....................................................................................................29
7.3.3 Visit 4 (Day 90 +/- 21) Administer Infant Module in Intervention Arms ..........29
7.3.4 Visit 5 (Day 109 +/- 21):  Post-Infant Intervention Data Collection ................29
7.4  
Final Visit 6 (Day 474 +/- 90) ..................................................................................30
7.5 
Withdrawal Visit ......................................................................................................30
7.6 
Unscheduled Visit ...................................................................................................30
8.
STUDY PROCEDURES /EVALUATIONS..........................................................................30
8.1 
Study Procedures/Evaluations................................................................................30
8.2 
Laboratory Procedures/Evaluations........................................................................35
8.2.1 Clinical Laboratory Evaluations...................................................................35
8.2.2 Special Assays or Procedures - Salivary bacterial analysis........................35
8.2.3 Specimen Preparation, Handling, and Storage...........................................35
8.2.4 Specimen Shipment....................................................................................35
9.
ASSESSMENT OF SAFETY ..............................................................................................35
9.1 
Specification of Safety Parameters.........................................................................35
9.1.1 Unanticipated Problems (UP)......................................................................36
9.1.2 Adverse Events...........................................................................................36
9.1.3 Serious Adverse Events..............................................................................36
9.2 
Time Period and Frequency for Event Assessment and Follow-Up .......................37
9.3 
Characteristics of an Adverse Event.......................................................................37
9.3.1 Relationship to Study Intervention ..............................................................37
9.3.2 Expectedness..............................................................................................37
9.3.3 Severity of Event.........................................................................................37
9.4 
Reporting Procedures.............................................................................................38
9.4.1 UP Reporting to IRB and NIDCR ................................................................38
9.5 
Halting Rules...........................................................................................................39
10.
STUDY OVERSIGHT .........................................................................................................39
11.
CLINICAL SITE MONITORING ..........................................................................................39
12.
STATISTICAL CONSIDERATIONS....................................................................................40
12.1 
Study Hypotheses...................................................................................................40
12.2 
Sample Size Considerations...................................................................................41
12.3 
Planned Interim Analyses (if applicable).................................................................42
12.4 
Final Analysis Plan..................................................................................................42
13.
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS...................43
14.
QUALITY CONTROL AND QUALITY ASSURANCE .........................................................44
15.
ETHICS/PROTECTION OF HUMAN SUBJECTS..............................................................45

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15.1 
Ethical Standard......................................................................................................45
15.2 
Institutional Review Board ......................................................................................45
15.3 
Informed Consent Process .....................................................................................45
15.4 
Exclusion of Women, Minorities, and Children (Special Populations) ....................46
15.5 
Subject Confidentiality ............................................................................................46
15.6 
Future Use of Stored Specimens and Other Identifiable Data................................47
16.
DATA HANDLING AND RECORD KEEPING ....................................................................47
16.1 
Data Management Responsibilities ........................................................................47
16.2 
Data Capture Methods............................................................................................47
16.3 
Types of Data..........................................................................................................48
16.4 
Schedule and Content of Reports...........................................................................48
16.5 
Study Records Retention........................................................................................48
16.6 
Protocol Deviations.................................................................................................48
17.
PUBLICATION/DATA SHARING POLICY..........................................................................48
SUPPLEMENTAL MATERIALS ..................................................................................................49
APPENDIX A: SCHEDULE OF EVENTS....................................................................................50
BIBLIOGRAPHY AND REFERENCES CITED............................................................................51

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LIST OF ABBREVIATIONS
AE
Adverse Event/Adverse Experience
ASTDD
Association of State and Territorial Dental Directors
BOP
Bleeding on Probing
BSS
Basic Screening Survey
CAN DO
Center to Address Disparities in Children’s Oral Health
CC
Coordinating Center
CFR
Code of Federal Regulations
CFU
Colony Forming Units
CP
CenteringPregnancy®
CPOP
CenteringPregnancy® Oral Health Promotion
CRA
Clinical Research Associate
CRF
Case Report Form
DHHS
Department of Health and Human Services
DSMB
Data and Safety Monitoring Board
eCRF
Electronic Case Report Form
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GLMM
Generalized Linear Mixed Model
HIPAA
Health Insurance Portability and Accountability Act
ICH
International Council for Harmonisation
ICMJE
International Committee of Medical Journal Editors
IRB
Institutional Review Board
KAB
Knowledge, Attitudes and Behaviors
LB
Lactobacillus
MS
Mutans Streptococci
N
Number (typically refers to subjects)
NIDCR
National Institute of Dental and Craniofacial Research, NIH, DHHS
NIH
National Institutes of Health
OCTOM
Office of Clinical Trials Operations and Management, NIDCR, NIH
OH
Oral Health
OHRP
Office for Human Research Protections
PD4
Probing Depth >4mm
PI
Principal Investigator

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PLI
Plaque Index
SAE
Serious Adverse Event/Serious Adverse Experience
SOP
Standard Operating Procedure
TVC
Total Viable Count
UP
Unanticipated Problem
US
United States

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PROTOCOL SUMMARY
Title:
CenteringPregnancy Oral Health Promotion (CPOP) Clinical Trial
Précis:
A five-year, Phase III, multi-site, cluster randomized controlled clinical 
trial will evaluate the efficacy of the CenteringPregnancy (CP) Oral 
Health Promotion (CPOP) intervention. Intervention and control groups 
will be drawn from 5 CP sites. Prenatal care facilitators will conduct the 
intervention in group prenatal care sessions. With 2-5 CP facilitators 
per site (14 facilitators), conducting 3-4 CP groups each (49 CP groups 
with 8 mother/child dyads per group), the total study population will be 
approximately 392 mother-child dyads. CP facilitators will be randomly 
assigned to either the: 1) intervention arm and deliver the CPOP 
intervention; or 2) control arm and deliver the usual CP curriculum. The 
CPOP intervention consists of two 15-minute modules: 1) maternal oral 
health (OH) and 2) infant OH. The data collection will continue through 
12 months postpartum. For the maternal OH module, pre- and post-
intervention dental exams of gingival OH and Plaque Levels, and 
knowledge, attitudes and behavior (KAB) questionnaires during the 
prenatal period will be used to assess maternal OH outcomes.  For the 
infant OH module, pre and post-module KAB questionnaires will be 
completed during the prenatal period. Infant OH risk status – the 
presence of caries-causing bacteria (mutans streptococci and 
Lactobacilli) in saliva of both mother and infant will be assessed when 
the infant is 12 months of age to determine differences in study arms. 
Analyses will include generalized linear mixed model regressions 
testing a treatment by time interaction to determine the significance of 
differences between intervention arms from pre-to post- intervention on 
the outcome variables. Additional analyses (Secondary Aim 2) will test 
mediation effects of knowledge, attitudes, and behaviors on 
relationships between treatment arm and primary study outcomes. 
Objectives:
Primary Aim 1: Determine if women in CP groups that include the 
CPOP intervention as part of their CP prenatal care will have 
significantly greater improvement in clinical OH and hygiene outcomes 
during pregnancy (reduced % sites with bleeding on probing (BOP), 
reduced % sites with probing depths ≥4mm (PD4), and reduced Plaque 
Index scores) compared to women receiving CP usual care.
Primary Aim 2: Determine if infants of mothers in CP groups that 
include the CPOP intervention as part of their CP prenatal care will be 
significantly less likely to have the presence of caries-causing salivary 

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bacteria (mutans streptococci) at 12 months of age, compared to 
infants of mothers receiving CP usual care.
Secondary Aim 1: Determine if women in CP groups that include the 
CPOP intervention as part of their CP prenatal care, compared to 
women receiving CP usual care will have significantly greater increases 
in: 
• Maternal OH knowledge, attitudes, and hygiene behaviors during 
pregnancy;
• Maternal infant-related OH knowledge and attitudes during 
pregnancy and at 12 months postpartum; and
• Maternal OH practices with their infant at 12 months postpartum.
Secondary Aim 2:  Determine if infants of mothers in the CPOP 
intervention groups are significantly less likely to have the presence of 
caries-causing salivary bacteria (Lactobacilli) at 12 months of age, 
compared to infants of mothers receiving CP usual care.
Secondary Aim 3: Determine if maternal OH knowledge, attitudes, 
and/ or behaviors mediate the relationships between intervention arm 
and maternal OH and infant OH risk (salivary bacteria incidence) 
outcomes. 
Population:
392 healthy mother-infant dyads coming from a broad range of socio-
demographic backgrounds. Women receiving their prenatal care in 
CenteringPregnancy® group prenatal care programs will be enrolled 
into the CPOP study from the 2nd through prior to the 3rd of their 10 
scheduled CP sessions. CP group care is available at clinics and 
hospitals in the San Francisco Bay Area. CPOP participants will be 
involved in the study from their study enrollment during pregnancy 
through 12 months postpartum. Women will participate during their 
pregnancies within their prenatal care sessions and data collection 
visits to complete assessments and dental examinations. Both mothers 
and infants will participate at 12 months postpartum.
Phase:
III
Number of 
Sites:
5 sites 
Description of 
Intervention:
The intervention consists of two 15-minute interactive modules 
(maternal and infant OH), integrated into 2 group prenatal care 
sessions. Led by trained prenatal care providers (facilitators), the 
maternal module includes discussion of common OH problems during 
pregnancy, importance of OH, importance and safety of OH care during 

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pregnancy, hands-on skills-building activities of learning and practicing 
proper tooth brushing and self-assessment of gum health, and 
presentation of illustrated flossing and OH promotion guides. The infant 
module includes discussion of infant oral hygiene, avoiding saliva 
sharing, proper nutrition, and importance of a dental visit by the first 
birthday. Activities in both modules utilize separate tool kits including 
tooth brushes, fluoride toothpaste, and other supplies.
Study 
Duration:
5 years
Subject 
Participation 
Duration:
Approximately 18 months  
Estimated 
Time to 
Complete 
Enrollment:
3 years 

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Schematic of Study Design:
Prior to  
  Randomize facilitators (n=14)
Enrollment
Visit 1
Day 0 
Visit 2
Day 14 ± 14
 
Visit 3
Day 84± 15
Visit 4
Day 90 ± 21
Visit 5
Day 109 ± 21
Visit 6
Day 474 ± 90
Total N=392:  Obtain informed consent. Screen potential subjects by inclusion and 
exclusion criteria; obtain history, document.
Perform baseline assessments –
dental exam; questionnaire; salivary assay
Follow-up assessments of outcome measures –
post-infant questionnaire
Follow-up assessments of outcome measures –
dental exam; post-maternal & pre-infant questionnaire
Final Assessments
Saliva collection from mother and 
infant for salivary bacterial assays; 
questionnaire
Arm 2
196 subjects
Arm 1
196 subjects
Administer CPOP intervention – 
Maternal Module
Administer CPOP intervention – 
Infant Module

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1. KEY ROLES AND CONTACT INFORMATION
Principal 
Investigators:  
Lisa H. Berens, DDS, MPH
3333 California St. Suite 495
San Francisco, CA 94118
(415) 476 2532
Lisa.Berens@ucsf.edu
Sally H. Adams, PhD, RN
3333 California St. Suite 245
San Francisco, CA 94118
(415) 502 7480
Sally.Adams@ucsf.edu
Medical Monitor:
Kevin McBryde, MD
6701 Democracy Blvd
MSC 4878
Bethesda, MD 20892-4878
(301) 594-0170
kevin.mcbryde@nih.gov
NIDCR Project 
Scientist:  
Darien Weatherspoon, DDS, MPH
6701 Democracy Blvd
MSC 4878
Bethesda, MD 20892-4878
(301) 594-5394
darien.weatherspoon@nih.gov
NIDCR Program 
Official:
Dena Fischer, DDS, MSD, MS
6701 Democracy Blvd
MSC 4878
Bethesda, MD 20892-4878

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Clinical Site 
Investigators:
(301) 594-4876
dena.fischer@nih.gov
N/A
Other Key 
Personnel:
Steven Gregorich, PhD
Ling Zhan, DDS, PhD
Yvonne Kapila, DDS, PhD
Guo-Hao Lin, DDS, MS
Margaret Hutchison, CNM, MSN
Matthew Brandner, BA
Lance Pollack, PhD  

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2. INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 
Background Information
Poor oral health during pregnancy for many women, low rates of oral health care 
utilization during pregnancy, and high rates of early childhood caries are public 
health problems: Rationale for developing oral health programs within prenatal 
care 
High rates of OH problems during pregnancy. Recognized as a sizable and largely 
preventable public health problem, maternal OH problems are very common during 
pregnancy, when susceptibility to periodontal disease is heightened1. Up to 70% of 
women2,3 develop pregnancy gingivitis, from hormonal, immunological and vascular 
reactions to irritants such as plaque. Though this usually subsides after childbirth, 
women with untreated gingivitis during pregnancy are more likely to have gingivitis after 
pregnancy4.  Caries prevalence, although not widely monitored during pregnancy, is an 
important factor in both maternal and infant OH. Recent studies indicate high caries 
prevalence in underserved pregnant populations5,6. These findings provide strong 
support for the guidelines that promote dental care, both for maintenance, and 
restorative treatments, during pregnancy. 
Low dental care rates during pregnancy. Despite high rates of perinatal OH problems, 
only 44% of women access dental care during pregnancy, evidence of great unmet 
need regarding treatment and/or education for OH problems during pregnancy that 
would benefit OH for mothers and infants7. This need is greatest within low-income 
populations. In California, among pregnant Medicaid enrollees, only 14% accessed 
dental care during pregnancy8.
High rates of early childhood caries in young children. While there is a trend of improved 
OH status for most age groups including young children in the U.S., still approximately 
one in four 2-5 year olds has either treated or untreated caries and the caries 
experience rate is double that for 6 – 8 year old children. Sizable disparities remain: 
higher rates are present in Hispanic and non-Hispanic Black children compared to non-
Hispanic White children, and in children from lower- income households compared to 
their peers in higher-income households9. Early research shows that mutans 
streptococci (MS) and Lactobacillus (LB) are the primary cariogenic bacteria in ECC10,11 
and are orally transmitted from caregiver to child12,13. Infants mainly acquire cariogenic 
bacteria from mothers through salivary transmission10,14, and mothers with high levels 
(>105 CFU/ml) are more likely to transfer bacteria to infants15. Reducing vertical 
bacterial transmission may reduce infant risk for ECC16-19. Thus, reducing vertical 
bacterial transmission should be included in OH promotion efforts during pregnancy. 
Federal agencies and national professional organizations have mounted a large effort to 
address these public health problems. The National Maternal and Child Health Bureau20 

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has released consensus statements and clinical guidelines on perinatal OH care during 
pregnancy. These evidence-based guidelines promote comprehensive strategies for 
both dental and non-dental clinicians with the noteworthy inclusion of prenatal care 
providers. Integrating OH care into perinatal care is consistent with the recommendation 
of the National Academy of Medicine (formerly known as the Institute of Medicine) to 
provide OH care in various settings utilizing a diverse and expanded array of 
providers21.  Including OH in prenatal care has the potential to improve women’s OH 
through improved preventive and restorative care and to promote children’s OH through 
caregiver education and timely anticipatory guidance.  
2.2 
Rationale
Rationale for integrating maternal and infant oral health interventions into 
CenteringPregnancy® group prenatal care
CenteringPregnancy® (CP) is an innovative prenatal group care model that provides 
evidence-based state-of-the-art prenatal care to women in a group setting. It was 
included in the AHRQ Health Care Innovations Exchange of programs that improve 
quality and reduce disparities. The CP model emphasizes 3 key elements to empower 
women to advance their health and that of their families: 1) healthcare; 2) health 
education; and 3) social support. Health education topics include nutrition, physical 
activity, tobacco/other substances cessation, partner relationships, prenatal problems, 
breast feeding, infant development and care, childbirth preparation, and postpartum 
issues. Oral health issues receive some mention but are not consistently addressed.
CP’s effectiveness for prenatal care delivery has been demonstrated in a randomized 
controlled trial22, and matched cohort study23 and is associated with lower preterm birth 
especially among low-income African American women, higher weights of preterm 
babies, and greater breast feeding compared to traditional care. CP is currently involved 
in a Center for Medicare & Medicaid Innovation award of $4 million to test 
implementation of the CP model into 15 organizations. The scope of these projects 
highlights the potential of CP group care to significantly improve maternal and child 
health. The addition of an evidence-based OH promotion intervention within CP has 
tremendous potential to contribute to those improvements. 
CP prenatal care typically includes 10 group sessions (about 2 hours in length) that 
typically begin early in the second trimester of pregnancy.  Sessions run for 
approximately 25 weeks in total. The first 4 sessions are 4 weeks apart and starting at 
Session 4, the remainder of the sessions are typically 2 weeks apart. CP emphasizes 
healthcare, health education, and community building or social support.  Approximately 
10 women of similar gestational phase make up each group. The women begin each 
session with recording their blood pressure, weight, and gestational phase and the 
facilitator conducts a standard prenatal assessment. Then, the women and the 
facilitator/s gather in a circle for a general check-in, facilitated discussion, and 
interactive activities addressing health topics relevant to the group’s gestation phase. 

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While CP usual care includes mention of maternal OH as one of the discomforts of 
pregnancy and infant OH as part of new baby care, OH is not consistently covered in a 
significant manner. 
This study will evaluate the ability of the CPOP intervention to improve the oral health 
and hygiene of women during pregnancy and to reduce the presence of caries-causing 
salivary bacteria in their infants at 12 months of age. Data on OH knowledge, attitudes, 
and practices will be collected to assess the hypothesized mechanisms of action of the 
intervention. While the CPOP pilot study showed significant effects of the intervention, a 
larger randomized trial is needed to confirm its efficacy prior to disseminating it to the 
larger audience of CenteringPregnancy nationwide.
2.3 
Description of the CPOP intervention
In this study, the CPOP study participants are recruited starting at Session 2 of the 
standard CP program and the CPOP maternal OH module will be delivered in the 3rd 
CP session when topic areas include a focus on maternal health issues.  Prior to 
administration of the intervention, participants will have a baseline dental examination, 
which will be compared to a post-intervention dental exam to assess the study’s primary 
outcome. CPOP intervention objectives cover the following: 1) a facilitated discussion to 
understand the common OH problems during pregnancy, the importance of maternal 
OH for mothers and infants and the importance of receiving OH care during pregnancy 
and routinely; 2) hands-on learning and practice of proper tooth brushing and 
performing the Eastman Interdental Bleeding Index toothpick test of gum self-
evaluation26; and 3) Illustrated handouts reinforcing discussion items, health practices, 
and instructions on proper tooth brushing and dental flossing. The Eastman toothpick 
test is performed by each participant at the beginning of their CP session. A toothpick is 
gently inserted interproximally 1-2mm at the gum line at 4 sites in their mouth, going in 
and out 4 times in the same spot. After a period of 15 seconds, the presence of 
bleeding is noted. A toolkit with OH supplies is provided for each woman. At subsequent 
CP sessions following the delivery of the maternal OH intervention, during the initial 
check in period when women check their blood pressure and weights, women also 
perform the Eastman toothpick test and record their results as a reinforcing activity to 
maintain attention on OH. CPOP pilot study results (n = 101) of the maternal OH 
intervention showed significant improvements in clinically assessed oral hygiene and 
gingival health: reduced % of gum sites that bled on probing, and reduced % of sites 
that were probed at ≥ 4mm depth. A slight, significant, increase was found in the 
intervention group for participants’ ratings of the importance of OH. OH knowledge and 
self-efficacy did not increase significantly. Similarly, tooth brushing and dental flossing 
did not improve in the intervention group compared to the control group24. 
The CPOP infant OH module is delivered in the 7th or 8th CP session when CP topic 
areas focus more on infant factors- development and care.  The CPOP infant OH 
module includes discussion of 5 objectives: the importance of baby teeth; avoiding 
saliva sharing; healthy feeding practices; cleaning and checking infant’s teeth and 

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gums; and importance of a dental visit by age 12 months. Infant OH tool kits are 
provided and used as reinforcing items for the objectives.  The primary outcome 
measure for the CPOP pilot study was salivary Mutans Streptococci (MS) prevalence in 
infants at 12 months of age. At 12 months, MS prevalence was significantly lower (7%) 
for the intervention group than for the control group (25%). At 12 months, the 
intervention group reported higher rates of initiating brushing their infants’ teeth, and 
cleaning infants’ gums than the control group. The groups did not differ significantly on 
feeding practices such as pre-tasting the infants’ food on his or her spoon or ensuring 
the infant has his or her own spoon. The intervention group demonstrated greater 
increases in mothers’ ratings of infant OH importance than the control group (p=0.003). 
Both groups reported significant increases in infant OH knowledge and the group 
difference was not significant. 
2.4 
Potential Risks and Benefits
2.4.1 Potential Risks
CP Women: Two maternal intervention behavioral activities: 1) practicing proper tooth 
brushing, which is a standard recommended health behavior known to prevent dental 
caries; and 2) practicing the Eastman toothpick test, have no known reported risks.  
There is a slight risk of physical discomfort from the two dental exams. There is 
potentially a slight risk of discomfort in answering some of the questions about dental 
behaviors in the questionnaire. There is no risk to mothers providing salivary specimens 
for bacterial level assessments.  There is a risk of a loss of confidentiality regarding 
participation in the study, which includes audio-recording of the intervention sessions 
delivered to the Intervention Arm participants. 
CP 12-month old Infants: There are no risks involved with wiping a cotton swab around 
the gum area, nor to providing salivary specimens for bacterial assessments.  
2.4.2 Potential Benefits
CP Women: Potential benefits include free dental exams for all women that include 
provision of basic feedback from the exam, including information about untreated decay 
and treatment needs. The women receiving the intervention may have increased OH 
knowledge, adopt favorable OH behaviors, and achieve better OH outcomes for 
themselves and their infants. Women receiving only the research evaluation procedures 
(dental examinations, salivary bacteria assessments, and questionnaires) in the control 
group may also adopt favorable OH behaviors which might result in better OH outcomes 
for themselves and their infants. 
CP Facilitators: The trained CP facilitators will gain experience and confidence in 
delivering the OH component which may expand their own knowledge of OH and 
professional development, and improve their own OH behaviors and outcomes. They 
may also increase the quality of assistance and support they provide to pregnant 
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General benefits: It is anticipated that the information obtained in the study will help in 
determining the efficacy of interventions to improve maternal OH during pregnancy and 
prevent the development of risk factors in infants postpartum. The information may help 
to identify patients who may benefit the most from the intervention. And if efficacious, 
the CPOP intervention could become part of the standard CP curriculum and be 
disseminated broadly to multitudes of pregnant women across the US and any future 
CP programs across the world.
3. OBJECTIVES
3.1
Study Objectives
3.1.1 Primary Objective 1 
Assess the efficacy of the CPOP intervention in improving maternal OH and hygiene 
during pregnancy.  We hypothesize that women in CP groups receiving the CPOP 
intervention will have significantly greater improvements in their OH outcomes 
(comparing post-intervention dental exam to baseline) than women in the usual care CP 
groups: reduced % sites bleeding on probing (BOP), reduced % sites with probing 
depths ≥4mm (PD4), reduced Plaque Index scores.
3.1.2 Primary Objective 2
Assess the efficacy of the CPOP intervention in promoting infant OH and caries risk 
reduction in the first year of life. We hypothesize that infants of mothers in CP groups 
that include the CPOP intervention as part of their CP prenatal care will be significantly 
less likely to have the presence of salivary MS at age 12 months, compared to infants of 
mothers receiving CP usual care.
3.1.3 Secondary Objective 1
Assess the efficacy of the CPOP intervention in improving the following: 1) Maternal OH 
knowledge, attitudes, and hygiene behaviors during pregnancy; 2) Maternal infant-
related OH knowledge and attitudes during pregnancy and at 12 months postpartum; 3) 
Maternal OH practices with their infant at 12 months post-partum. We hypothesize that 
women who receive the CPOP OH interventions will have greater increases in these 
three sets of indicators. 
3.1.4 Secondary Objective 2
Assess the efficacy of the CPOP intervention in reducing the likelihood that infants of 
mothers in CP groups that include the CPOP intervention as part of their CP prenatal 
care will develop the presence of salivary LB at age 12 months, compared to infants of 
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3.1.5 Secondary Objective 3
Determine if maternal OH knowledge, attitudes, or behaviors mediate the relationships 
between intervention arm and maternal OH and infant OH risk (presence of salivary 
bacteria) outcomes.  We hypothesize that the primary mechanism of action for improved 
maternal OH in the CPOP intervention would be improvement in oral hygiene practices 
(tooth brushing – change in brushing technique, frequency and/or length of time spent 
brushing, and flossing skills). Improvements in these practices could be due to and 
reinforced by increases in the following: oral hygiene skills, self-efficacy to improve and 
maintain good OH, OH knowledge, and perceived importance of good OH. We 
hypothesize that the mechanisms of action in reduction in infant oral health risk status 
include skills building in infant oral hygiene practices which would be promoted by 
increases in infant OH self-efficacy, knowledge, and importance of good infant OH.
3.2 
Study Outcome Measures
3.2.1 Primary Outcomes
Outcomes for Primary Objective 1:  Maternal outcomes: Clinical measures of bleeding 
on probing, periodontal probing depths ≥4mm; and plaque levels compared between the 
2 intervention arms from pre- to post- intervention during pregnancy. 
Outcomes for Primary Objective 2: Infant outcomes: Clinical infant measures of 
presence of salivary MS compared between the 2 intervention arms assessed at infant 
age 12 months.
3.2.2 Secondary Outcomes
Outcomes for Secondary Objective 1: Questionnaire measures of maternal OH 
knowledge, attitudes, and behaviors compared from pre- to post- for the 2 intervention 
arms; questionnaire measures of maternal knowledge and attitudes regarding infant OH 
promotion assessed during pregnancy and at 12 months postpartum; maternal infant 
care behavior differences.
Outcomes for Secondary Objective 2: Infant outcomes; clinical measures of presence of 
salivary LB between the 2 intervention arms at 12 months postpartum.
Outcomes for Secondary Objective 3:  Mediation outcomes for maternal OH are 
maternal OH knowledge, attitudes (importance and self-efficacy), and behaviors (ADA-
recommended tooth brushing practices and flossing). Mediation outcomes for infant OH 
risk are infant OH-related knowledge and attitudes (importance and self-efficacy).
4. STUDY DESIGN
Overview of Research Design. We will conduct a cluster randomized controlled clinical 
trial to evaluate the efficacy of the CPOP intervention within the CP prenatal care group 
environment. The intervention will take place during the prenatal period and participants 

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will be assessed pre-intervention and post-intervention while still pregnant and followed 
through the first year postpartum to evaluate infant and maternal outcomes.  
Intervention Setting. The study will take place at 5 healthcare facilities that offer CP in 
the San Francisco Bay Area, most of which are community-based.  The initiation of study 
activities in sites will be staggered in three waves approximately nine months apart, with 
two sites starting in each wave. CP groups at these 5 sites are conducted in either 
English or Spanish. We will recruit a minimum of 2-5 CP facilitators at each site to serve 
as either intervention or control facilitators. Facilitators will be randomized to one of two 
groups: 1) Intervention or 2) Control. Intervention facilitators will be trained in the 
intervention, which will include the facilitators practicing the Intervention delivery in a 
group of non-study CP moms. When study groups are initiated, the facilitators will 
conduct the interventions in approximately 3-4 cycles of prenatal groups. In each cycle, 
intervention facilitator will integrate the 2 intervention modules into 2 of their 10 CP group 
sessions. Control facilitators will not be trained and will not present the intervention 
modules within their CP groups. The control groups will receive the usual care CP 
curriculum. CP groups consist of 8-12 pregnant women of a similar gestational phase.
CP Facilitators. We have identified a Site Champion at each CP site, an individual with 
influence and connection to the clinical and administrative leadership at the health care 
facility. Study staff will work with these Site Champions to present an overview of the 
study to the facilitators and to ask them to enroll in the study. They will be assured that 
they are free to participate or not, however, they will be aware that their site had made a 
group decision to participate. The facilitators will be randomized into the Intervention or 
the Control arm of the study. This means that all of the pregnant women enrolled in a 
particular facilitator’s assigned CPOP study groups will either be Intervention or Control 
participants.  
CPOP Study Participants. Pregnant women enrolled in the CP prenatal care groups 
identified as study groups at each site will be invited to participate in the study. We 
expect that most but not all women will agree to participate in the study. However, within 
the Intervention CP groups, all of the women will receive the OH-integrated intervention 
modules (unless unenrolled women choose not to), but only enrolled study participants 
will complete the study questionnaire assessments and dental exams, and the salivary 
bacterial assays and questionnaires at 12 months postpartum. As explained above the 
CPOP moms will not be randomized, but rather their study group arm will be determined 
by their facilitator’s randomly assigned place in the Intervention or the Control arm. Both 
Intervention and Control participants will receive OH tool kits at the time of the scheduled 
CPOP modules in the Intervention groups (CP session 3 for Maternal module and 
sessions 7 or 8 for Infant module).
CP Women participants’ and CP Facilitators’ data collection.
CP Women: At baseline and prior to the first (Maternal) of the two modules, participants 
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activities will be scheduled for completion at the CP clinic site, outside of CP group 
scheduled time. A trained calibrated dental examiner will complete the dental exams in a 
private space, using portable dental equipment: chair, lamp, and stools. Study staff will 
administer the questionnaires and enter results directly into a tablet or laptop. The dental 
exam takes about 15-20 minutes and the questionnaires take about 15 minutes. 
The Maternal Intervention Module.  Intervention groups will receive the CPOP maternal 
intervention as part of their 3rd CP group session. Refer to Section 6.5 for details.
Approximately 10 weeks following the time of the maternal module and prior to the infant 
intervention module, participants complete the post-maternal module assessments 
consisting of a repeat dental exam and questionnaire completion. At this time, women 
also complete the pre-infant intervention module assessments. These consist of 
questionnaire assessment of infant OH knowledge and attitudes. Women receive their 
incentives within a week following completion of the assessments. 
The Infant Intervention Module. The infant module is presented as part of the 7th or 8th 
CP session. Refer to Section 6.5 for details.
Approximately 2 weeks following the presentation of the Infant OH module, participants 
complete the post-infant OH module questionnaire assessment, repeating the earlier 
pre-module assessment. This may be done online with REDCap, email, or over the 
phone with an interview process.  Women receive their incentives within a week following 
completion of the assessments. This is the final activity to occur during the prenatal 
period.  Participants will receive a note from the study thanking them for their participation 
up to this point and reminding them that we will stay in touch with them about the study 
and will follow-up with them when their infants are about 10 months of age to schedule 
the 12-month postpartum visit. 
When an infant is approximately 10 months of age, study staff will contact families to 
remind them of the final assessment to take place at infant age 12 months. We will 
assess eligibility of the infant to participate in the follow-up and confirm mother’s intention 
to complete the final assessment. If the infant is ineligible to participate, the mother will 
still be eligible to complete the final assessment. The 12-month visit time will be 
scheduled. 
The 12-month visit will occur at the participant’s home or another location that is 
convenient for the mother and baby.  Women will complete questionnaires and saliva 
collection procedures for assessment of salivary bacteria. The infants will complete a 
saliva collection procedure. Women receive their incentives within a week following 
completion of the assessments. 
CP Facilitator participants:  The CP facilitators will complete assessments of acceptability 
and feasibility of the CPOP Intervention at the time that study activities have come to a 
close in their clinics. This will include evaluation of their: satisfaction with the training and 
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groups; perceived value of CPOP to CP moms; perceived scalability of the interventions 
into the broader standard CP curriculum; and overall perceptions of the benefits versus 
burdens associated with the changes needed to accommodate CPOP modules in CP 
sessions. These data will help inform future implementation when CPOP is scaled up and 
disseminated broadly. These will be done online through REDCap.  
5. STUDY ENROLLMENT AND WITHDRAWAL
5.1 
Subject Inclusion Criteria
CP Facilitators: 

CP facilitators who conduct CP groups within the 5 designated study sites;

ages 18 and older speak, read, and write in English;

provide informed consent 
CP Women: 

speak, read, or write in English or Spanish

enrolled in CP prenatal group care identified as study groups 

free of any condition that requires them to take antibiotic or antibacterial 
medication prior to dental procedures

provide informed consent 
CP Babies: 

healthy with no acute or chronic medical conditions, especially those conditions 
that may have resulted in hospitalizations and subsequent exposure to 
pathologic microorganisms

mothers provide informed consent for their children at baseline  
Dental Exam Calibration Participants: 

ages 18 and older 

free of any condition that requires them to take antibiotic or antibacterial 
medication prior to dental procedures 

provide informed consent
5.2 
Subject Exclusion Criteria
None

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5.3 
Strategies for Recruitment and Retention
CP Facilitators: Facilitators will be recruited from the 5 partner CP sites and will be 
randomly assigned to be either intervention or control facilitators. Facilitators will receive 
incentives, resources for their groups including CP notebooks, and food and beverages 
for the group refreshments. 
CP Women receiving care in CP groups led by enrolled CPOP study facilitators: Study 
staff will attend the 2nd CP session and give a brief presentation describing study 
purpose, activities, time needed and duration of participation, incentives, options to 
participate, and protection of confidentiality. Women who are interested in participating 
can either stay after the group to get more information and/or sign informed consent, or 
they can give contact information and receive a follow up phone call to get more 
information and/or to agree to participate. The CP participant will receive reminders by 
text or email about their participation in the study and congratulations on their baby’s 
birth and birthday cards. Our CP clinical sites vary in size. Estimates of women 
receiving CP care annually at the sites range from 53 – 176 per site (total estimated 
number annually who will join in CP groups led by one of the 14 study-participating CP 
facilitators = 340). All of our sites state that their programs are strong or robust and half 
of them also indicate that they are growing in size. 
Calibration participants: Flyers will be posted at UCSF and other close locations to 
advertise the recruitment for participants. Interested adults will contact the CRA staff to 
get more information about the study, to determine eligibility, and receive instruction for 
attending the calibration session. Participants will sign consent when they arrive for the 
session. The CRA will send a follow up message to the participants with a reminder of 
the session time and date 3 days prior to the session.   
5.4 
Treatment Assignment Procedures
CP facilitators who are randomized to be an intervention arm facilitator will deliver the 
intervention to their CP participants. CP facilitators who are randomized to be a control 
arm facilitator will not deliver the intervention to their CP participants. Facilitators will 
know their assignment prior to the pregnant women in their groups being enrolled, but 
will be trained not to disclose this to the women.
5.4.1 Randomization Procedures 
CP Facilitators will be randomly assigned to either Intervention or Control arm according 
to a matched, restricted randomization plan. Intervention facilitators will receive CPOP 
training after assignment. Our primary concern is strengthening the basis for causal 
inference by establishing equivalent experimental groups at baseline. Randomizing 5 
sites is not optimal and randomizing CP participants is not possible because the 
intervention is delivered to CP groups. Therefore, we have chosen to randomize 14 CP 
facilitators, using “restricted randomization”25 to ensure an acceptable level of balance 
across experimental groups at baseline (e.g., create two sets of CP facilitators balanced 
on preexisting variables describing relevant characteristics of CP sites, facilitators, and 
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the other to deliver usual care). Prior to randomization we will identify facilitators from 
our five clinical sites who agree to accept assignment as an Intervention or a Control 
facilitator.  Once identified, we will collect descriptive data characterizing each 
participating CP site and facilitator, as well as the populations they serve; these data will 
be included in the restricted randomization process. Intervention facilitators will receive 
CPOP training approximately 2 months before site initiation. 
Originally, we planned to randomize CP facilitators into two sets of equal size (i.e., 7 CP 
facilitators assigned to each set).  However, with summary data in hand, preliminary 
restricted randomization solutions with equal set size failed to establish reasonable 
cross-set balance on variable describing characteristics of CP sites, facilitators, and 
their served populations.  Next, we allowed for set sizes of with 8 and 6 CP facilitators, 
respectively. Allowing for an '8/6' split resulted in several restricted randomization 
solutions that balanced CP site, facilitator, and patient population characteristics within 
close tolerances.  Therefore, we opted to randomize CP facilitators into two groups with 
one group including 8 CP facilitators and the other including 6 CP facilitators.  Once a 
final '8/6' split was chosen, the study statistician flipped a coin to assign the two sets to 
CPOP Intervention versus usual care control. 
5.4.2 Masking Procedures 
CP Facilitators: At each CP site, CRAs will recruit the CP facilitators with the help of the 
CP Site Champion, specific to the CP site.  Each CP Site Champion is a CP facilitator 
who agreed to participate in the study and to be randomized to either study arm.  
Training of CP Intervention facilitators at each CP site will initiate 2 months before their 
site is scheduled to begin recruiting patients into the study; at each CP site all CP 
facilitators within a CP site will be blind to random assignments until training of CP 
facilitators begins at their site. 
CP Study Participants: Participants will complete informed consent that indicates that 
they may be in a CP group in which they receive additional information and activities 
related to their oral health and the health of their infants. They will not know whether 
they are in a CP group that will include the CPOP intervention until they have completed 
their enrollment and baseline activities. After enrollment, masking women or facilitators 
will not be possible.  All dental examinations and salivary bacteria assays will be 
conducted with the evaluator masked to intervention or control arm.
5.5 
Subject Withdrawal
CP Facilitators are free to withdraw from the study at any time, without penalty or loss of 
status at their CP clinics.
CP Participants are free to withdraw from and stop participation in the study at any time, 
for any reason, without penalty or loss of services at their clinics. Participants may be 
withdrawn for safety reasons in the case of an adverse event. 

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5.5.1 Reasons for Withdrawal
CP Facilitators may withdraw if they are transferred to a different CP clinic or move, if 
they feel that their work schedules are too demanding to remain involved in the study, or 
for other personal reasons.
CP women might withdraw from the study because they are moving to another location, 
have a miscarriage, leave the CP group care setting due to health risk reasons, decide 
to convert to traditional 1:1 prenatal care, or do not wish to continue in it. Women who 
miss the CPOP intervention module/s will be retained in the study, their attendance (yes 
versus no) will be recorded. 
5.5.2 
Handling of Subject Withdrawals or Subject Discontinuation of 
Study Intervention
If a CP facilitator withdraws from the study, she/he will be removed from the study and 
another facilitator at the site will be recruited to replace her/him. 
If a CP participant withdraws from the study, the study staff will document the reason 
and will remove them from the study. Withdrawn participants will not be replaced. 
5.6 
Premature Termination or Suspension of Study
We do not anticipate any circumstance that would necessitate premature termination or 
suspension of the study. The study will not yield any early outcomes that would indicate 
that it should be stopped prior to completion. The previous pilot studies were 
categorized as minimal risk, we had high adherence to protocol requirements using the 
same methods, and there were no adverse events. 
This study may be suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to NIDCR and 
regulatory authorities.  If the study is prematurely terminated or suspended, the principal 
investigator will promptly inform the IRB and will provide the reason(s) for the 
termination or suspension. 
Circumstances that may warrant termination include, but are not limited to:

Determination of unexpected, significant, or unacceptable risk to subjects.

Insufficient adherence to protocol requirements.

Data that are not sufficiently complete and/or evaluable. 

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6. STUDY INTERVENTION
6.0 Adaptations to comply with UCSF requirements and guidelines for 
conducting research with human subjects during the COVID-19 pandemic 
At this time, October 2020, we are not conducting any research activities with human 
subjects. We were ready to commence study activities 3 days prior to the COVID-19 
pandemic coming into full focus and thus all activities were halted. Since then, we have 
been in regular communication with our 5 clinical study locations regarding their status 
of resumption of conducting prenatal care in the group setting, the timing of which has 
not been determined. Prior to resuming activities, we will work with the UCSF IRB, the 
UCSF School of Dentistry, and each clinical location’s oversight leadership to determine 
and adhere to all safety guidelines and requirements associated with implementation 
and completion of our study activities. This includes conducting our facilitator training 
activities and the following intervention modules in our intervention groups:  group 
discussions about oral health topics, and hands on instruction and practice of proper 
toothbrushing technique and learning to conduct the Eastman toothpick test, a self-
assessment of gum health. 
We are unable to specify details of the adaptations that we will implement at the 
time of study resumption because the timing of clinical resumption of group activities 
and the full extent of adaptations to be required is not fully known at this time. We will 
submit a Protocol modification addressing these to the IRB when the necessary details 
have been determined.   
6.1 
Study Behavioral or Social Intervention(s) Description
The CPOP intervention consists of two 15-minute interactive, discussion- and skills-
based modules (one maternal, one infant) that fit within the CP facilitative framework. 
Each module utilizes a tool kit for participants containing oral hygiene supplies. 
The Maternal Intervention Module:
This is presented in the 3rd CP session when the session topics focus on maternal needs 
and care. (See Section 2.2 for description of timing of CP Sessions.). The facilitator: 
1) Introduces the topic of OH during pregnancy and distributes OH tool kits 
containing a toothbrush, toothpaste, and dental floss. 
2) Leads an interactive discussion of: 1) common OH problems and asks women to 
share their experiences with these; 2) the importance of OH for the mother and 
the infant; and 3) the importance of receiving dental care during pregnancy and 
routinely afterwards. During this, the women are encouraged to discuss their 
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the women’s basic knowledge and will direct and expand explanations as needed 
to clarify facts versus folk beliefs.  
3) Discusses the importance of OH self-care and will lead the group in step by step 
tooth brushing instructions and dry brushing practice, using supplies from the tool 
kits. The facilitator will give feedback as needed for each woman. She will explain 
the rationale for learning the Eastman Interdental Assessment26 and will instruct 
and guide the women to do the assessment using toothpicks and mirrors. In 
subsequent CP sessions, the women will conduct the toothpick test at the 
beginning of their sessions which is a check in time during which they monitor 
and record their weights and blood pressures and receive an assessment from 
the prenatal care provider facilitators. Women will have attended their baseline 
dental exams and the presence of severe periodontal issues will have been 
brought to their attention with the recommendation that they seek treatment as 
soon as possible.
4) Distributes 2 illustrated pages: 1) instructions for proper tooth brushing and 
flossing technique; and 2) summary review of the important elements for good 
OH. 
The Infant Intervention Module:
The infant OH module is generally done around the 7th or 8th session when session 
topics focus increasingly on infant care and development. The facilitator:
1) Introduces the topic of infant OH and distributes OH tool kits containing a 
toothbrush, toothpaste, a small plastic- BPA-free spoon, and a small soft cloth for 
cleaning the inside of the infant’s mouth. 
2) Leads an interactive discussion of: 1) the importance of baby teeth; 2) proper 
feeding practices emphasizing the avoidance of saliva-sharing practices; 3) the 
timing of beginning oral hygiene and proper practices for this; and 4) the 
importance of the first dental visit by age 1 year.   
3) Distributes an illustrated review of the important elements for good infant OH.
6.2 
Administration of Intervention
The interventions will be delivered by the trained CP facilitators in the CP sessions. 
There are 2 intervention modules, a maternal module and an infant module. These will 
be delivered within CP groups in the intervention arm only. Each module lasts about 15 
minutes. All women in the CP group in the intervention arm will be invited to receive the 
intervention regardless of their participation status (yes vs. no) in the study. CP group 
sessions are usually conducted with 2 clinicians, a facilitator and co-facilitator. CP group 
sessions take place in a closed room with the women and clinicians sitting on chairs in a 
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6.3 
Procedures for Training Interventionists and Monitoring Intervention 
Fidelity
Facilitators attend a 2-3- hour training session, typically conducted in a group setting.  
The training has 3 components:
1) A didactic session led by Dr. Berens (PI) that covers the rationale for the CPOP 
intervention and the evidence base for the components of the CPOP intervention 
modules including learning objectives and activities. 
2) A step-by-step walk through of implementing the CPOP intervention (discussion 
and hands-on activities) by CP Consultant Laurie Jurkiewicz.
3) A role play session of the intervention modules using the intervention materials 
presented by Ms. Jurkiewicz.
4) Question and answer period to discuss integration of the modules into the routine 
CP sessions, issues that facilitators see arising in their groups, etc.
We had originally planned that facilitators would do an intervention practice session in a 
non-study CP group.  However, we learned that the facilitators’ group schedules are 
varied and not reliably scheduled closely enough together to be able to have a 
“practice” group and a study group in close proximity timewise. We therefore revised the 
plan in the following manner. The facilitators will conduct a practice session with study 
staff role playing as CP mom participants.  Facilitators receive feedback and 
suggestions from research staff as needed.
Facilitator presentation of each CPOP intervention module is audio recorded and 
assessed by the study research staff for completeness of presentation of the 
intervention objectives. The research assessment of the audio recordings includes the 
following: Dr. Adams will train 1 CRA to complete the intervention fidelity scoring 
assessment; will establish inter-rater reliability; then do a final check by evaluating 4 
audio recorded sessions and again comparing both sets of ratings for reliability. If the 
inter-rater reliability on the 4 evaluations is >85%, we will designate the CRA to score 
the subsequent audio recordings. Reliability refreshers will be conducted and re-
assessed annually. 
6.4 
Assessment of Subject Compliance with Study Intervention
The skills-building activities for the women (tooth brushing and the Eastman toothpick 
test) will include practicing them during the intervention period. During the maternal 
module session, the facilitator will observe the women while they practice brushing their 
teeth and will assist any women who do not appear to be doing it properly. 
Subsequently, at each of the remaining CP sessions, the women will complete the 
toothpick test at their check-in time and will review the results with their facilitator. Also, 
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to indicate whether each woman participated actively in the module activities.  Women 
who do not attend an Intervention session or do not participate will be considered 
missing and will be retained in the ITT analysis. Missed attendance at OH module 
sessions will be considered a protocol deviation.   
7. STUDY SCHEDULE
7.1 
Screening and Recruitment
A study staff member will attend the second CP session to provide a brief overview of 
the study and invite women to seek further information by staying after the session or 
providing contact information for a follow up phone call. Eligibility will be described: 
women enrolled in CP care will be eligible to participate in CPOP if they are free of any 
condition that requires them to take antibiotic or antibacterial medicine prior to dental 
examinations or treatment. Women may enroll on that same day by staying after the CP 
session to have questions answered and to sign consents, or they could be enrolled at 
the time of follow-up phone contact. Women enrolled by phone can complete informed 
consent using the REDCap and DocuSign systems or can receive consent forms via 
email which they can review and bring with them to Visit 1 and sign prior to completing 
baseline data collection activities.
7.2 
Baseline Data Collection (Visit 1, Day 0)
Women will be recruited between the 2nd CP session and the 3rd CP session (See 
Section 7.1). Visit 1 Data Collection procedures will be scheduled in that same time 
period to occur prior to the presentation of the CPOP maternal intervention module that 
will be conducted at Session 3. Consent will be verified and documented. Inclusion 
criteria will be confirmed. Both intervention and control groups will complete the 
following: 

Questionnaire assessments (demographics, oral health status, oral 
health knowledge, attitudes, behaviors

Saliva specimen collection

Dental examinations
7.3 
Intermediate Visits 
7.3.1 Visit 2 (Day 14 ± 14) Maternal Intervention Administration
The range of +/- days is broad because the baseline data could be collected in a range 
of approximately 28 days between CP sessions 2 and 3, but prior to the administration 
of the CPOP Maternal Module in CP Session 3.  

Takes place among participants in the Intervention arm only

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
Administer the maternal OH module in Intervention Arm

Record participation and attendance at the intervention
7.3.2 Visit 3 (Day 84+/- 15): Post-Maternal & Pre-Infant Intervention Data 
Collection

Takes place prior to administration of the CPOP Infant Module occurring 
in Session 7 or 8

Post-Maternal Intervention and Pre-infant Intervention questionnaire 
assessments

Dental Examinations
7.3.3 Visit 4 (Day 90 +/- 21) Administer Infant Module in Intervention Arms

Administer Infant Intervention

Record attendance
7.3.4 Visit 5 (Day 109 +/- 21):  Post-Infant Intervention Data Collection 

Collect post-infant intervention and participant acceptability assessment 
questionnaires
7.4 
Final Visit 6 (Day 474 +/- 90)
Data collection at infant approximate 12 months of age

Questionnaire assessments

Maternal salivary bacterial assay specimen collection

Infant salivary bacterial assay specimen collection
7.5 
Withdrawal Visit
Women who withdraw from the study will be queried to determine their reasons for 
withdrawal.   
7.6 
Unscheduled Visit
N/A

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8. STUDY PROCEDURES /EVALUATIONS
8.0 Procedures/Evaluations adaptations to comply with UCSF requirements and 
guidelines for conducting research with human subjects during the COVID-19 
pandemic 
As mentioned above in Section 6, we are not currently conducting any research 
activities with human subjects. Prior to resuming activities, we will work with the UCSF 
IRB, the UCSF School of Dentistry, and each clinical location’s oversight leadership to 
determine and adhere to all safety guidelines and requirements associated with 
implementation and completion of our study activities. These include the collection of 
the following research data: in person on-line questionnaires, dental examinations 
including periodontal probing, saliva specimen collection from mothers and from their 
infants when they are approximately one-year of age at the 1-year follow up.
8.1 
Study Procedures/Evaluations
Table 1: Assessment variables
Primary (1°) Outcome Variables
Measures
Base-
line
Mid-
Study1
Mid-
Study2
Final 12 
mo.
Maternal Oral Health
Gingival Status
Periodontal pocket depth
Bleeding on probing
X
X
X
X
Maternal Oral Hygiene
Oral Hygiene
Plaque Index
X
X
Infant Oral Health
Bacteria levels 
Salivary MS
X
Secondary (2°) Outcome Variables
Measures
Maternal OH-related
Knowledge, Attitudes Behaviors
Questionnaire
X
X
X
Infant OH-related
Knowledge, Attitudes, Behaviors of 
the mothers
Questionnaire
X
X
X
Infant Oral Health
Bacteria levels 
Salivary LB, TVC
X
Descriptive (D) variables
Measures
Demographics
Questionnaire
X
Maternal periodontal status
Clinical attachment levels
X
Maternal caries
ASTDD BSS untreated caries
X
X
Maternal bacteria levels
Salivary MS, LB, TVC
X
X
Table 1 describes the components of the assessments, outcome variables, and 
measures. TVC= total viable count
QUESTIONNAIRE AND CLINICAL EVALUATIONS

Questionnaire assessments:  

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We will collect questionnaire data via electronic survey completion at 4 time points in 
the study, using REDCap, a clinical trials management software program.  For 
participants who request, the CRA will administer the questionnaires verbally.
1. Baseline:  Demographic; Pre-Maternal questionnaire
This includes basic demographic information, self-reported OH status, dental care 
utilization, OH knowledge, attitudes, and practices. It takes approximately 15 
minutes to complete. Items on the questionnaire have been used in previous studies 
in similar populations27, including the pilot study, and determined to be acceptable.  
2. Mid-Study 1: Post-Maternal (1) and Pre-Infant questionnaire 
The first post-maternal assessment is a repeated measure of the baseline maternal 
assessment. The pre-infant assessment includes questions regarding knowledge 
about infant oral health, attitudes, proper infant oral hygiene and feeding practices, 
and self-efficacy items to prevent infant OH problems. 
3. Mid-Study 2: Post-infant questionnaire (1); Participant Acceptability 
4. Final 12-month post-partum: Post-Maternal (2) questionnaire; Post-Infant 
questionnaire (2); Participant Acceptability 
The second post-maternal and post-infant assessments are repeated measures.  

Dental examinations: Dental examinations will be conducted at baseline prior to the 
maternal module, and at Mid-Study 1 (following the maternal module and prior to the 
infant module). There are three components: 1) Plaque Index; 2) gingival 
assessment including bleeding on probing, pocket depths, and clinical attachment 
levels (attachment levels at baseline only); 3) need for treatment and referrals for 
dental care based on the ASTDD Basic Screening Survey.
A portable dental unit will be utilized for the dental exams. It will be set up at the CP 
clinic in a space where the privacy of the procedure and confidentiality of any results 
will be maintained. The dental unit includes a patient chair, examiner chair, and 
assistant chair. No radiographs will be taken. The total examination will take 
approximately 15 minutes. A trained and calibrated dentist or dental hygienist will 
conduct all dental exams. The trained dental assistant/research assistant will be 
responsible for setting up supplies, entering data into the laptop computer, and 
providing proper storage and security of all data.  

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Prior to starting the exam, the examiner will screen the participant for the presence 
of any contraindications for receiving a periodontal exam. These include requiring 
antibiotic prophylaxis prior to a dental procedure due to the following heart 
conditions: 1) artificial heart valves; 2) a history of infective endocarditis; 3) a cardiac 
transplant with abnormal heart valve function; or 4) certain specific, serious 
congenital heart conditions (unrepaired or incompletely repaired cyanotic congenital 
heart disease including those with palliative shunts and conduits; a completely 
repaired congenital heart defect with prosthetic material or device for the first six 
months after the repair procedure; or any repaired congenital heart disease with 
residual defect such as persisting leaks or abnormal flow, at the site or adjacent to 
the site of a prosthetic patch or a prosthetic device). We are retaining the screening 
activity to assure that women have not acquired any contraindication subsequent to 
enrolling in the CPOP study.  In the event that a woman has acquired a 
contraindication by the time of the second dental exam, she will remain a study 
participant and will receive only the plaque evaluation and Need for Treatment 
assessments.  
A Microsoft Access electronic data entry program for dental exams (updated from 
the original CPOP pilot study) will be utilized for data capture. Other equipment and 
supplies will include mouth mirrors, periodontal probes, gauze, disposable gloves, 
eye protection, and other barrier protection for proper infection control. Reusable 
instruments will be sterilized at the UCSF School of Dentistry. Universal infection 
control guidelines and procedures will be followed. 
The dental examination includes three procedures:
1. Oral Hygiene - Plaque Index (PI)
Plaque recording is important as a diagnostic, preventive, and treatment aid. For this 
study, we will use a modified plaque index (PI) developed by Silness and Löe, 
196428.
Criteria for Plaque Index are the following:
0
No plaque
1
A film of plaque adhering to the free gingival margin and adjacent area of the tooth. 
Plaque may be seen in situ only with disclosing solution or probing. (Light plaque) 
2
Moderate/heavy accumulation of soft deposits within the gingival pocket, or on the 
tooth and the gingival margin. Can be seen with the eye without using an instrument.

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2. Gingival assessment: Gingival status will be assessed with full-mouth exams by 
measuring gingival recession and probing pocket depth to derive periodontal 
clinical attachment levels; and gingival bleeding on probing at baseline and post 
maternal module intervention. Changes in gingival status related to changes in 
oral hygiene (probing pocket depth and bleeding on probing) can be detected 
within the time frame we have designated for our pre-post dental examination. 
While attachment levels will be measured at baseline to characterize the sample, 
only probing pocket depth and bleeding on probing (not attachment levels) will be 
measured at mid-study post-maternal intervention.
3. Need for treatment and referrals for dental care: Though not a study outcome 
measure, as an obligation and service to the participants we will determine the 
need for treatment based on the protocol detailed in the Basic Screening Survey 
(BSS) developed by the Association of State and Territorial Dental Directors 
(ASTDD)29. For adults, the indicators include cavities, adults with one or more of 
their own teeth (as opposed to false teeth), and urgency of need for dental care. 
Criteria for determining dental treatment need are the following:
Category
Recommendation for
next dental visit
Criteria
Code 2: Urgent or 
emergency need for 
dental care
As soon as possible
Signs or symptoms that include pain, infection, 
swelling, or soft tissue ulceration of more than two 
weeks duration (determined by questioning)
Code 1: Early dental 
care is needed 
Within several weeks 
Caries without accompanying signs or symptoms, 
individuals with spontaneous bleeding of the gums, 
suspicious white or red soft tissue areas, or an ill-
fitting denture are coded “1”
Code 0: No obvious 
problems
Routine dental care 
(next regular checkup)
Any patient without above problems
Oral health status information and recommendations for dental care will be 
provided to the participant along with a list of local dentists/dental clinics 
accepting Medicaid insurance and pregnant patients. 

Saliva collection:  Saliva will be collected from the mother at baseline and both 
mother and baby at 12 months postpartum. It will be carried out by the CRA at a 
location and time convenient to the participant. The CRA will be trained in the 
following salivary collection techniques by Co-Investigator Dr. Ling Zhan.

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Stimulated saliva collection from the mother: Two ml of stimulated saliva will be 
collected from mothers at least 2 hours after tooth-brushing or any food or beverage 
consumption. The mothers will be asked to chew on a wax tablet (Ivoclar Vivadent 
Inc., NY, USA) and expectorate into a test tube until 2 ml of stimulated saliva are 
collected.
Swab sample collection from the infant: An oral swab sample will be obtained from 
the child: 1) at least 1 hour after the last feeding and; 2) at least 2 hours after 
cleaning of the oral cavity. Sterile cotton-tipped applicators (CITMED Citronelle, AL) 
will be swabbed over the gingiva, tongue, oral mucosa, and tooth surfaces until the 
swab is saturated with saliva. The tip will be broken off and dropped into a pre-
labeled 5 ml sample tube with 2 ml of reduced transport fluid (RTF)30,31.
The test tubes containing saliva from the mother and child will be specially coded 
and no subject identification information will be used. The samples will be 
transported on ice by the RA to the microbiology laboratory at UCSF for total viable 
count (TVC), mutans streptococci (MS), and lactobacillus (LB) plating and culture 
within 24 hrs.
PROCESS EVALUATION OF IMPLEMENTATION
We will track participation and completion rates for purposes of evaluating 
implementation. These rates will be utilized to establish overall CPOP implementation 
fidelity and overall rate of assessment procedure completion. (See Section 11 
Statistical Considerations)
Components of 
implementation
Definition of components32
(Based on Linnan and Steckler, 2002)
Reach
(Recruitment/Participation 
rate)
The proportion of women who are recruited, enrolled, and 
participate out of all invited women 
Dose delivered 
(Delivery rate)
CPOP modules - proportion of planned sessions that were 
conducted 
Dose received
(Attendance rate)
Proportion of the CPOP modules that participants received  
Fidelity
(Estimated fidelity rate)
Proportion of the learning objectives addressed in the CPOP 
modules  

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8.2 
Laboratory Procedures/Evaluations
8.2.1 Clinical Laboratory Evaluations
None
8.2.2 Special Assays or Procedures - Salivary bacterial analysis
Microbiological assays: Salivary assays will be performed under the guidance of Dr. 
Ling Zhan in her laboratory at UCSF. Maternal and infant saliva will be assayed for 
Mutans Streptococci (MS), Lactobacillus (LB), and Total Viable Count (TVC). 
8.2.3 Specimen Preparation, Handling, and Storage
Saliva specimen storage, handling and banking for future studies: Each saliva sample 
will be labeled with study ID and collection date. Once transported to the microbiology 
lab, the samples will be plated immediately or stored in a 4º refrigerator for plating within 
24 hours, all under the care and supervision of Dr. Zhan. The saliva samples will be 
destroyed according to biological hazardous waste guidelines immediately following the 
microbiological assays. The access to the samples will be logged in a laboratory log 
sheet. No saliva will be banked for future studies. 
8.2.4 Specimen Shipment
Specimens will not be shipped
9. ASSESSMENT OF SAFETY
9.1 
Specification of Safety Parameters
Because participants represent vulnerable populations, special attention will be given to 
any adverse events that occur during the study. The CPOP takes place in the health 
care setting in which participants receive their prenatal care. The CP facilitator who 
conducts the CPOP intervention in each CP group (participant’s prenatal care provider) 
will be present and aware of each woman’s physical condition during the CPOP study. 
Safety reporting for the study will focus on serious adverse events (SAEs) or 
unanticipated problems related to study interventions that occur during the course of the 
study. 
9.1.1 Unanticipated Problems (UP)
The Office for Human Research Protections (OHRP) considers unanticipated problems 
(UPs) involving risks to subjects or others to include, in general, any incident, 
experience, or outcome that meets all of the following criteria:

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
unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied;

related or possibly related to participation in the research (“possibly related” 
means there is a reasonable possibility that the incident, experience, or outcome 
may have been caused by the procedures involved in the research); and

suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized.
9.1.2 Adverse Events
An AE is any untoward or unfavorable medical occurrence in a human subject, including 
any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in the 
research, whether or not considered related to the subject’s participation in the 
research.
AEs will be recorded and monitored to ascertain their frequency, severity, and nature, to 
determine whether they are related to study activities, and thus would reflect an 
Unanticipated Problem, which would be reported.  
9.1.3 Serious Adverse Events
A serious adverse event (SAE) is one that meets one or more of the following criteria:

Results in death

Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred)

Results in inpatient hospitalization or prolongation of existing hospitalization

Results in a persistent or significant disability or incapacity

Results in a congenital anomaly or birth defect  

An important medical or dental event that may not result in death, be life 
threatening, or require hospitalization may be considered an SAE when, based 
upon appropriate medical judgment, the event may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition.
9.2 
Time Period and Frequency for Event Assessment and Follow-Up
UPs will be recorded in the data collection system throughout the study. 

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The PI will record all events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation.  At each study visit, the investigator will inquire about the occurrence of 
AE/SAEs since the last visit.  Events will be followed for outcome information until 
resolution or stabilization.
9.3 
Characteristics of an Adverse Event
9.3.1 Relationship to Study Intervention
To assess relationship of an event to study intervention, the following guidelines are 
used:
1. Related (Possible, Probable, Definite)
a. The event is known to occur with the study intervention.
b. There is a temporal relationship between the intervention and event onset.
c. The event abates when the intervention is discontinued.
d. The event reappears upon a re-challenge with the intervention.
2. Not Related (Unlikely, Not Related)
a. There is no temporal relationship between the intervention and event 
onset.
b. An alternate etiology has been established.
9.3.2 Expectedness 
The PIs will be responsible for determining whether an AE is expected or unexpected.  
An adverse event will be considered unexpected if the nature, severity, or frequency of 
the event is not consistent with the risk information previously described for the 
intervention.  
9.3.3 Severity of Event
The following scale will be used to grade adverse events:
1. Mild: no intervention required; no impact on activities of daily living (ADL)
2. Moderate: minimal, local, or non-invasive intervention indicated; moderate impact 
on ADL
3. Severe: significant symptoms requiring invasive intervention; subject seeks 
medical attention, needs major assistance with ADL

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9.4 
Reporting Procedures
Federal regulations and the UCSF IRB/HRPP require investigator reporting of any post-
approval research-related event or information that may meet the HRPP’s institutional 
definitions of “unanticipated problem involving risk to participants or others” or “serious 
or continuing noncompliance.” The IRB/HRPP reviews the reports and determines 
whether they meet the institutional definition of a UP, among other things.
9.4.1 UP Reporting to IRB and NIDCR
Incidents or events that meet the OHRP criteria for unanticipated problems require the 
creation and completion of an unanticipated problem report form. OHRP recommends 
that investigators include the following information when reporting an AE, or any other 
incident, experience, or outcome as an UP to the IRB:

appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number;

a detailed description of the adverse event, incident, experience, or outcome; 

an explanation of the basis for determining that the adverse event, incident, 
experience, or outcome represents an unanticipated problem; 

a description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the unanticipated problem.
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline:  

UPs that are SAEs will be reported to the IRB and to NIDCR within 5 working 
days of the investigator becoming aware of the event. 

Any other UP will be reported to the IRB and to NIDCR within 10 working days of 
the investigator becoming aware of the problem. 

All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or 
designee), and OHRP within one month of the IRB’s receipt of the report of the 
problem from the investigator.
All UPs will be reported to NIDCR’s centralized reporting system via Rho Product 
Safety:

Product Safety Fax Line (US):  1-888-746-3293

Product Safety Fax Line (International):  919-287-3998

Product Safety Email:  rho_productsafety@rhoworld.com 

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General questions about SAE reporting can be directed to the Rho Product Safety Help 
Line (available 8:00AM – 5:00PM Eastern Time):  

US:  1-888-746-7231

International: 919-595-6486
9.5 
Halting Rules
If an UP develops that is a significant threat to the safety of participants, or if the 
number of SAEs overall or the number of occurrences of a particular type of SAE raises 
concerns, the NIDCR may temporarily suspend enrollment until a safety review is 
convened. The objective of such a review would be to decide whether the study should 
continue per protocol, proceed with caution, be further investigated, be modified and 
then continued, or be discontinued.
10.STUDY OVERSIGHT
In addition to the PIs’ responsibility for oversight, study oversight will be under the 
direction of a Data and Safety Monitoring Board (DSMB) appointed by the NIDCR. The 
DSMB will operate under the rules of an NIDCR-approved charter that will be approved 
at the organizational meeting of the DSMB. The conduct of the DSMB and rules 
regarding how often the Board will meet will be defined by the DSMB charter for the 
study. At this time, most data elements that the DSMB needs to assess will be clearly 
defined. It is anticipated that the DSMB will meet at least once per year via 
teleconference to assess safety and efficacy data, study progress, and data integrity for 
the study. If safety concerns arise, more frequent meetings may be held. The DSMB will 
provide recommendations to the NIDCR.
11.CLINICAL SITE MONITORING  
Clinical site monitoring is conducted to ensure that the rights of human subjects are 
protected, that the study is implemented in accordance with the protocol and/or other 
operating procedures, and that the quality and integrity of study data and data collection 
methods are maintained. Monitoring for this study will be performed by NIDCR’s Clinical 
Research Operations and Management Support (CROMS) contractor. The monitor will 
evaluate study processes and documentation based on NIDCR standards and the 
International Council for Harmonisation (ICH), E6: Good Clinical Practice (GCP) 
guidelines.
Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) 
developed by the CROMS contractor, in collaboration with the NIDCR Office of Clinical 
Trials and Operations Management (OCTOM) and the NIDCR Program Official. The 
CMP will specify the frequency of monitoring, monitoring procedures, the level of clinical 
site monitoring activities (e.g., the percentage of subject data to be reviewed), and the 
distribution of monitoring reports. Some monitoring activities may be performed 

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remotely, while others will take place at the study site(s). Staff from the CROMS 
contractor will conduct monitoring activities and provide reports of the findings and 
associated action items in accordance with the details described in the CMP.  
Documentation of monitoring activities and findings will be provided to the site study 
team, the study PIs, OCTOM, and the NIDCR. The NIDCR reserves the right to conduct 
independent audits as necessary.
Monitoring visits will include, but are not limited to: review of site assessment and staff 
training; human subjects protection; protocol compliance; regulatory compliance; 
laboratory SOPs and compliance; laboratory sample disposition, storage, and handling; 
quality assurance; adverse event reporting; and integrity of research data and samples. 
12.STATISTICAL CONSIDERATIONS
12.1 Study Hypotheses
Primary Hypothesis 1: Women in CP groups that include the CPOP intervention as part 
of their CP prenatal care will have significantly greater improvement in clinical OH and 
hygiene outcomes during pregnancy (reduced % sites bleeding on probing (BOP), 
reduced % sites with probing depths ≥4mm (PD4), reduced Plaque Index (PI) scores 
compared to women receiving CP usual care.
Primary Hypothesis 2: Infants of mothers in CP groups that include the CPOP 
intervention as part of their CP prenatal care will be significantly less likely to have the 
presence of salivary MS at age 12 months, compared to infants of mothers receiving CP 
usual care.
Secondary Hypothesis 1:  Women in CP groups that include the CPOP intervention as 
part of their CP prenatal care, compared to women receiving CP usual care will have 
significantly greater increases in: 
A. Maternal OH knowledge, attitudes, and hygiene behaviors during pregnancy;
B. Maternal infant-related OH knowledge and attitudes during pregnancy at 12 
months postpartum; and
C. Maternal OH practices with their infant at 12 months postpartum.
Secondary Hypothesis 2: Infants of mothers in CP groups that include the CPOP 
intervention as part of their CP prenatal care will be significantly less likely to have the 
presence of salivary LB at age 12 months, compared to infants of mothers receiving CP 
usual care.
Secondary Hypothesis 3: Maternal OH knowledge, attitudes, and/or behaviors will result 
in significant mediation of the relationships between intervention arm and maternal OH 
(plaque levels, BOP and PD4) and infant OH risk (salivary bacteria incidence) 
outcomes.

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12.2 Sample Size Considerations
Sample size estimate and power analyses. We assume 80% power; two-tailed =0.05; 
75% retention at 12 months; binary outcomes describing maternal gingival 1) pocket 
depth ≥4mm (PD4) and 2) bleeding on probing (BOP) at each probed site (max=168; in 
pilot data =159 sites per participant); 3) a continuously coded maternal plaque index 
𝑥
score (PI: range 0-4); and 4) a child-level binary MS colonization indicator. The PD4 and 
BOP data for mothers will have a 5-level nested structure with a) 5 CP sites, b) 2-5 CP 
facilitators per CP site for a total of 14 CP facilitators participating in the study, c) 3-4 CP 
groups per facilitator for a total of 49 CP groups with participants enrolled in the study, 
and, on average, e) 8 study-enrolled mother-child dyads per CP group, and f) 159 
gingival probe sites per mother; the maternal PI data and the child-level MS data will 
share the first four levels. The total sample size estimate is 392 mother-child dyads (49 
CP groups  8 mother-child dyads/CP group results in a total of 392 month-child dyads). 
Power analyses assumed two randomized groups including 8 and 6 CP facilitators, 
respectively. From our pilot data, we estimated intra-cluster correlations (ICC) for 
maternal PD4 equal to 0.001 for CP sites, facilitators, and groups, as well as 0.13 for 
CP women; ICCs for BOP equaled 0.04 for CP sites, facilitators, and groups, as well as 
0.27 for CP women; ICCs for maternal PI equaled 0.13 for sites and 0.14 for facilitators 
and groups; ICCs for the child MS outcome equaled 0.01 for CP sites and CP 
facilitators as well as 0.04 for CP groups.
We present power to detect the 
effect sizes observed in our 
pilot study as well as the 
minimum detectable effects 
with 80% power. We note that 
although the observed effect on 
MS (OR=4.77) is considered 
'large,' two reasons to choose 
the proposed design are that it, 
conservatively, is capable of detecting a 'medium' sized effect on MS (OR=2.71) and, 
more importantly, it is capable of detecting the smaller effect sizes anticipated on 
maternal outcomes. For the mediation test to help explicate mechanisms of action we 
further assumed a correlation of 0.30 between experimental groups and a unit-
standardized continuous mediator describing maternal OH behavior: the minimum 
detectable indirect effect of experimental groups on the binary child MS indicator 
corresponded to an OR=1.3033. Power was calculated by simulation via multilevel 
logistic models with Laplace estimation; the simulations also suggested that for the 
proposed experimental design, the modeling framework produces unbiased parameter 
and standard error estimates.
observed effect in pilot
min. detectable effect
BOP: Ctrl v Intv
  (mothers)
16.7% v 10.7%
OR=1.67, power>0.97
16.7% v 11.8%
OR=1.50, power=0.80
PD≥4mm: Ctrl v 
Intv (mothers)
20.4% v 17.0%*
OR=1.25, power=0.80
20.4% v 17.0%*
OR=1.25, power=0.80
PI (means) Ctrl v 
Intv (mothers)
0.95 v 0.76
d=0.41, power=0.89
0.95 vs 0.78
d=0.37, power=0.80
MS: Ctrl v Intv
  (children)
24.9% v 6.5%
OR=4.77, power=0.97
24.9% v 10.9%
OR=2.71, power=0.80
* observed and minimum detectable effects equivalent w/in rounding;
d represents a group difference of standardized means

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12.3 
Planned Interim Analyses (if applicable)
No planned interim analyses.
12.4 
Final Analysis Plan
Proposed statistical analyses: Descriptive analyses will estimate means and 
proportions, measures of variability, and confidence intervals (CIs). We will determine 
whether participant baseline characteristics are independent of intervention group 
assignment (randomization check) and attrition (attrition analysis).
Missing data. Case-wise deletion of missing data will not be used for analysis because it 
relies on the relatively strong missing completely at random assumption and entails a 
loss of statistical power. Instead, multiple imputation will allow models to be fit to all 
available data and will invoke the relatively mild assumption that the data are missing at 
random, conditional on modeled variables34-37.
Primary Analyses will include intention-to-treat comparisons. The multilevel data 
structure will be accommodated by generalized linear mixed models (GLMMs) with 
random intercepts for CP centers, facilitators, groups, mothers/children, and repeated 
assessments (for maternal outcomes; PROC GLIMMIX). Main outcomes include 
binomial indicators of mothers' BOP (# sites bled/# sites probed) and PD4 (# sites with 
≥4mm pocket depth/# sites probed,) continuous indicator of maternal plaque levels, and 
a binary outcome of child oral MS colonization (multilevel logistic regression via Laplace 
estimation); and a count of child MS colonization (multilevel zero-inflated Poisson or a 
zero-inflated negative-binomial model, as appropriate, via Laplace). Each maternal 
outcome will be regressed onto indicators of experimental groups and assessment time, 
as well as the group-by-time interaction. Child MS outcomes at 12-months will be 
regressed onto the experimental group indicator. Significant intervention group main 
effects at follow-up and group-by-time interaction effects will be interpreted and 
described. If any key demographic or risk factors are imbalanced at baseline, we will 
include a quintile-stratified propensity adjustment, which can significantly reduce bias38-
40. Propensity scores will be estimated by regressing the intervention group indicator 
onto baseline characteristics of participants (averaged up to the unit of randomization); 
covariate balance across groups will be assessed41. Next, propensity score quintiles will 
be formed. Regression models will initially include a quintile-by-groups-by-time 
interaction term to test whether the intervention effect is equivalent across quintiles. A 
significant interaction term would suggest quintile-specific treatment effects, which 
would then be estimated and reported. If the interaction term is non-significant, then it 
would be removed and the intervention effect estimated, conditional on the propensity-
quintile main effect. 
Secondary analyses will include multilevel linear models of secondary outcomes: OH 
knowledge, self-efficacy, importance, behavior scores; and multilevel binary and zero-
inflated count outcome models of child LB and TVC levels. Additional multilevel models 
will explore whether any intervention effects are moderated by maternal race/ethnicity, 

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language, socioeconomic status, CP site, and baseline maternal OH knowledge and 
behaviors. 
Mediation analyses to help assess mechanisms of action: We will test whether 
experimental group assignment impacts subsequent hypothesized maternal OH 
behavior mediators measured at the mid-study assessment period, as well as whether 
indirect effects of intervention groups on child MS outcomes via the candidate mediators 
are significant. Mediation will be tested with a series of linear, binary, and zero-inflated 
multilevel models, as appropriate, using methodological extensions to accommodate 
binary mediators and outcomes42-44. A draft interim analysis plan will be developed in 
case the U01’s DSMB requires interim analyses; an alpha-spending function with 
O’Brien-Fleming rule will be proposed to control Type I error.
Descriptive analyses of facilitator perceived feasibility and acceptability of the CPOP 
intervention within CP clinics and group sessions: When study activities have been 
completed in the CP sites, Intervention facilitators will complete acceptability and 
feasibility assessments. The purpose of these is to provide evaluation of the perceived 
impact of the CPOP interventions integrated into CP sessions in terms of value to CP 
moms, value to the CP programs, and burdens/challenges (time constraints, adjusting 
topic schedules) versus benefits in CP groups. 
13.SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS
Study staff will maintain appropriate research records for this study, in compliance with 
ICH E6, Section 4.9 and regulatory and institutional requirements for the protection of 
confidentiality of subjects. No patient medical records will be accessed. Study staff will 
permit authorized representatives of NIDCR and regulatory agencies to examine (and 
when required by applicable law, to copy) research records for the purposes of quality 
assurance reviews, audits, and evaluation of the study safety, progress and data 
validity.  
Source documents include informed consent forms. Informed consent will be obtained 
and maintained within the REDCap system which utilizes the IRB-approved DocuSign 
mechanism associated with REDCap for participant signature completion. Paper forms 
will be utilized when the REDCap system is not available and will be kept in locked file 
cabinets, separate from all other participant records. The web-based Clinical Trials 
Management Software (CTMS) system REDCap will be the original source for 
scheduled and actual study visits; dental examination data; questionnaire data; adverse 
event reports, and protocol deviations. Salivary assay data will be recorded in a lab 
notebook and entered electronically into REDCap.
Whenever possible, data will be entered directly into a computer. Based on available 
data, the rate of possible system failure is estimated at <1%. In the eventuality of a 
system outage or internet service failure, back-up paper forms for data capture and 
subsequent system entry are available.

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14.QUALITY CONTROL AND QUALITY ASSURANCE
The Data Manager (DM) will serve as the Quality Management Coordinator, and in 
coordination with the Clinical Research Coordinator (CRC), will utilize clinical trials 
monitoring systems available through REDCap, NIDCR, and/or CROMS documents to 
monitor quality control of all study activities. This will include the documentation and 
maintenance of records, and generation of regular reports for both internal (within study 
team) and quarterly and/or annual reports, as scheduled, to the NIDCR. These will 
provide the status of study preparation (including CRC and CRA trainings, facilitator 
interventionist trainings, dental examiner trainings and calibration sessions and results, 
partner clinic preparations) and study activities (including participant recruitment, clinical 
partner site activities, activities completion including intervention deliveries by sites and 
by CPOP participant, CRF completion, incentives dispersal, and data (withdrawals) and 
safety (AE, SAE) monitoring). All of these major activities will utilize checklists to ensure 
and document completion of procedures. (More details can be found in the Data 
Management Plan and the Quality Management Plan).    
A.
Recruitment and tracking. UCSF CRA staff will be trained on procedures and 
scripts, will use eligibility checklists, and will document study eligibility. Participant 
personal identifying information will be maintained in a secure location (REDCap) to 
allow tracking across study activities. 
B.
Consent procedures. Informed consent will be obtained by UCSF CRA staff. 
Participants will complete consents in REDCap and sign them using DocuSign. 
Documentation of informed consent will be maintained in REDCap.  
C.
Assessment completion. All CRC and CRA study staff will be trained to complete 
data collection processes. All staff trainings will be documented as to activity and date 
completed. Assessment completion will be overseen and recorded by date in REDCap. 
1) CRAs will be trained to administer questionnaires and will enter the completion dates 
into the monitoring system, which will be verified by the REDCap data 2) The examiner 
will conduct the exam and the CRA will enter dental exam data into an Access database 
and document the completion of exams into REDCap. 3) CRAs will collect saliva 
specimens and will document in REDCap their completion and delivery to the clinical 
lab.  
D.
Intervention training, delivery, and fidelity monitoring. CPOP interventions will be 
delivered by CP facilitators who are trained by study investigators/personnel and 
evaluated for fidelity to the training plan. Training binders and toolboxes will be utilized 
to increase standardization and fidelity. Facilitators will conduct a practice session with 
study staff serving as intervention recipients, and receive feedback on the facilitator 
presentation of the intervention. All trainings will be documented and facilitators will 
receive refresher training annually. New facilitator CPOP interventionists will receive the 
same training. All actual intervention sessions will be documented and audiotaped for 
fidelity monitoring purposes. Facilitators will receive feedback to address any issues 

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identified in the fidelity evaluation. (More details can be found in the Intervention 
Training and Fidelity Manual).
E.
Dental examiners training and calibration. Dental examiners will attend trainings 
and calibration sessions conducted by our Periodontal Co-Investigator team of Drs. 
Kapila and Lin. Trainings will be focused on conducting the Plaque Index, gingival 
measures of bleeding on probing, periodontal pocket depths, clinical attachment levels, 
and the ASTDD Basic Screening Survey protocol. Calibrations will be conducted for the 
Plaque Index and Periodontal pocket depth probing levels. Examiners will undergo 
initial training and calibration and recalibrated annually. Calibration participants will be 
recruited from the UCSF Campus Area and will include adults 18 years and older who 
are free of any condition that requires them to take antibiotic or antibacterial medication 
prior to dental procedures. 
15.ETHICS/PROTECTION OF HUMAN SUBJECTS
15.1 
Ethical Standard
The investigator will ensure that this study is conducted in full conformity with the 
principles set forth in The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research, as drafted by the US National Commission 
for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 
1979) and codified in 45 CFR Part 46 and/or the ICH E6. 
15.2 Institutional Review Board
The protocol, informed consent forms, recruitment materials, and all subject materials 
swill be submitted to the IRB at UCSF for review and approval.  Approval of both the 
protocol and the consent forms must be obtained before any subject is enrolled.  Any 
amendment to the protocol will require review and approval by the UCSF IRB before the 
changes are implemented in the study.  
15.3 
Informed Consent Process
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation.  Consent forms will 
be required for the calibration participants, CP facilitator participants, and CP women 
participants, who also consent for their babies in their original baseline consent forms.  
Reconsent for the baby is necessary only in the event of a protocol change. Extensive 
discussion of risks and possible benefits of study participation will be provided to 
subjects and their families, if applicable. A consent form describing in detail the study 
procedures and risks will be given to the subject via email or on paper. Consent forms 
will be IRB-approved, and the subject is required to read and review the document or 
have the document read to him or her. The investigator or designee will explain the 
research study to the subject and answer any questions that may arise. Study 
participants will include both English and Spanish speakers. Spanish language consent 

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forms will be provided and the CRAs recruiting in Spanish-language CP groups will be 
fluent Spanish-speakers. The subject will sign the informed consent document prior to 
any study-related assessments or procedures.  Subjects will be given the opportunity to 
discuss the study with their surrogates or think about it prior to agreeing to participate. 
They may withdraw consent at any time throughout the course of the study. A copy of 
the signed informed consent document will be given to subjects for their records. The 
rights and welfare of the subjects will be protected by emphasizing to them that the 
quality of their clinical care will not be adversely affected if they decline to participate in 
this study.
The consent process will be documented in REDCap.  
15.4 
Exclusion of Women, Minorities, and Children (Special Populations)
The proposed CPOP clinical trial participants will include facilitators of the CP prenatal 
program, pregnant women, and eventually, their newborn infants. There are no 
exclusion criteria involving gender status. Males are not excluded, but it is unlikely that 
there will be male facilitators in the CP organization. However, if there are male 
facilitators, they will be eligible for participation in the study. All the CP women will be 
pregnant females. We will enroll all eligible infants of participating mothers, female and 
male.
15.5 
Subject Confidentiality
Subject confidentiality is strictly held in trust by the investigators, study staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
samples in addition to any study information relating to subjects.
The study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the sponsor.
The study monitor or other authorized representatives of the sponsor may inspect all 
study documents and records required to be maintained by the investigator, including 
but not limited to, medical records (office, clinic, or hospital) for the study subjects.  The 
clinical study site will permit access to such records.
A slight risk of disclosure of confidential information exists including dental exam results, 
salivary bacterial levels, and oral health behaviors. Research records will be handled as 
confidentially as possible. All study data used for research purposes will contain only a 
study ID and have names, addresses, and other information removed for data analysis 
so they cannot be identified by name. They will be kept in locked files available only to 
those persons requiring access for research purposes. No individual identities will be 
used in any reports or publications resulting from the CPOP trial. No identifying 
information will be transmitted from the clinical site or UCSF to NIDCR or the DSMB.

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15.6 
Future Use of Stored Specimens and Other Identifiable Data
N/A
16.DATA HANDLING AND RECORD KEEPING
The Principal Investigators are responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. All source documents should be 
completed in a neat, legible manner to ensure accurate interpretation of data. The 
investigators will maintain adequate case histories of study subjects, including accurate 
case report forms (CRFs), and source documentation.
16.1 
Data Management Responsibilities
Staff will utilize a secure web-based data-entry and clinical trials management software 
(CTMS) system REDCap (Forte Research Systems) to input questionnaire and clinical 
data and to monitor study participant status. Each staff person will have a unique login 
ID with strong passwords and access and permissions restricted to data consistent with 
their given roles within the study. Each participant will be assigned a unique study ID 
number to be used on each electronic case report form for identification and tracking 
purposes.
Systems and procedures will comply with HIPAA. Multiple methods will be used to 
secure the electronically gathered data. In addition to unique IDs for each staff member, 
passwords will be required to have a specific length and combination of alphanumeric 
and special characters to mitigate social hacking of passwords. Operating system and 
software updates will be performed on a routine basis to ensure systems are hardened 
against hacking attempts. 
Daily server backups will be performed. Data are stored using encryption. The servers 
are housed in the UCSF Medical Center data center (ECDC), providing state-of-the-art 
physical and electronic security. REDCap servers are guarded by multiple firewall and 
intrusion detection systems. Backup data files are kept in a secured environment and 
are available for recovery.
16.2 
Data Capture Methods
Questionnaires will be self-administered in English or Spanish directly into 
REDCap with either the text presentation or upon request administered to 
them through an interview process. Dental exam results will be directly 
entered into an Access database that will be saved in Excel spreadsheets 
and then uploaded into the REDCap system. Any system modifications or 
refinements will be validated. Later, lab results of salivary assays, 

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including levels of MS, LB, and TVC, will be recorded in Excel 
spreadsheets as CFU/ml along with sampling date, processing date, 
counting date, and then uploaded into REDCap. 16.3 
Types of Data
Informed consent will be collected electronically except in the cases of no internet 
access when paper consents will be used and stored as the source document. 
Electronic case report forms will include dental examination data (periodontal 
measurements, plaque levels, caries prevalence), questionnaire responses, and 
salivary assay data as well as completion of intervention and assessment activities. 
16.4 
Schedule and Content of Reports
Periodic reports documenting study progress will be generated by REDCap and 
reviewed by PIs and co-investigators at monthly meetings. These reports include: (i) a 
tabular enrollment report that summarizes enrollment progress, number of participants 
who completed the study protocol, number of participants who discontinued early; (ii) a 
listing of each subject deviation and protocol deviation with dates, descriptions, and 
actions taken; (iii) a listing of participant study activities (e.g., questionnaire, dental 
exam) that were missed; (iv) a report with graphical and tabular summaries of 
cumulative (versus planned) accrual and follow-up visit attendance; and (v) a report 
summarizing dental exam data collected. 
Reports will be presented to the DSMB on a schedule that they determine.  
16.5 
Study Records Retention
The study will maintain participant records including data from dental exams and 
salivary assays from pregnant women and their babies. These records will be retained 
based on recommendations from the NIH, or if no guideline is established, based on the 
UC Vice Provost for Research guideline, which is that records be kept for 7 years after a 
child reaches the age of maturity (18 in California) for minors, and for 25 years for 
pregnant women.  
16.6 
Protocol Deviations
Protocol deviations and violations are unplanned deviations/violations from/of expected 
protocols.  Protocol violations are serious unplanned occurrences that could reduce the 
quality of the data, for example a scheduled intervention module that did not take occur. 
Protocol deviations include study activities that occur outside of expected parameters 
that are not considered a threat to the quality of the data.  For example, a scheduled 
intervention module that did not occur in the planned session but was delivered in a 
subsequent CP session would be identified as a protocol deviation.  Other examples 
include assessment activities that a participant does not complete within the expected 
window or misses completely. Facilitator-level protocol violations and deviations will be 
recorded initially in Excel and monitored in REDCap. Participant-level deviations will be 
recorded directly in REDCap. All will be reported to the NIDCR, UCSF IRB, and the 
DSMB, according to their requirements.

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17.PUBLICATION/DATA SHARING POLICY
This study will comply with the NIH Public Access Policy, which ensures that the public 
has access to the published results of NIH funded research. It requires scientists to 
submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital 
archive PubMed Central upon acceptance for publication.
If determined to be a condition for publication, the CPOP trial will be registered in a 
public trials registry such as ClinicalTrials.gov, per the International Committee of 
Medical Journal Editors (ICMJE) policy.  
As with all NIDCR-supported research, all materials submitted for publication, 
publications and reports resulting from activities supported by this award will 
acknowledge support from the National Institute of Dental and Craniofacial Research, 
NIH, specifically referencing the grant number.
An acknowledgment shall be made to the effect that:
"The project described was supported by Award Number 1U01DE027340-01from the 
National Institute of Dental & Craniofacial Research. The content is solely the 
responsibility of the authors and does not necessarily represent the official views of the 
National Institute of Dental & Craniofacial Research or the National Institutes of Health.”
Following completion of the study, the investigators will prepare manuscripts of the 
results to be submitted to peer-reviewed scientific journals for publication. 
Authorship
Investigators will decide on authorship of scientific documents prior to writing them.  The 
principles set forth in the ICMJE Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals (the “Vancouver Rules”) will be followed.  These standards can be 
reviewed online at http://www.icmje.org/.
SUPPLEMENTAL MATERIALS
With the exception of the Schedule of Events included in Appendix A, the listed 
documents are relevant to the protocol, but they are not considered part of the protocol.  
They are stored and modified separately. 
Appendix A: Schedule of Events (included)
Manual of Procedures
Data Management Plan
Quality Management Plan

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Intervention Training and Fidelity Manual
Questionnaire assessments
Consent forms
Dental Examination Training and Calibration Manual

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APPENDIX A: SCHEDULE OF EVENTS
Assessment variables, measures, and time points
6 months
1 year
CP sessions 2-10/Assessment time points
Primary (1°) Outcome 
Variables
Measures
2
BL
3
4
5
6
MID
1
7
8*
MID
2
9
10
Post-
partum
12 mo.
Maternal Oral Health
Gingival Status
Periodontal pocket depth
Bleeding on probing
1°
1°
MM
1°
1°
IM
Maternal Oral Hygiene
Oral Hygiene
Plaque Index
1°
MM
1°
IM
Infant Oral Health
Bacteria levels 
Salivary MS
MM
IM
1°
Secondary (2°) Outcome 
Variables
Measures
Maternal OH-related
Knowledge, Attitudes 
Behaviors
Questionnaire
2°
MM
2°
IM
2°
Infant OH-related
Knowledge, Attitudes, 
Behaviors of the mothers
Questionnaire
MM
2°
IM
2°
2°
Infant Oral Health
Bacteria levels 
Salivary LB, TVC
MM
IM
2°
Descriptive (D) variables
Measures
Demographics
Questionnaire
D
MM
IM
Maternal periodontal 
status
Clinical attachment levels
D
Maternal caries
ASTDD BSS untreated 
caries
D
D
Maternal bacteria levels
Salivary MS, LB, TVC
D
MM
IM
D
Maternal Module
   Infant Module (may be delivered in Session 7 or 8*)
BL=baseline assessment; MID=mid-study assessments
MM
IM

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Bibliography and References Cited
1.
Laine MA. Effect of pregnancy on periodontal and dental health. Acta 
odontologica Scandinavica. Oct 2002;60(5):257-264.
2.
American Dental Association Council on Access Prevention and Interprofessional 
Relations. Oral Health Care Series: Women's Oral Health Issues 2006; 
http://www.ada.org/sections/professionalResources/pdfs/healthcare_womens.pdf
. Accessed September 19, 2012, 2012.
3.
Armitage GC. Bi-directional relationship between pregnancy and periodontal 
disease. Periodontology 2000. Feb 2013;61(1):160-176.
4.
Zeeman GG, Veth EO, Dennison DK. Focus on primary care: periodontal 
disease: implications for women's health. Obstet Gynecol Surv. Jan 
2001;56(1):43-49.
5.
Weintraub JA, Finlayson TL, Gansky SA, Santo W, Ramos-Gomez F. Clinically 
determined and self-reported dental status during and after pregnancy among 
low-income Hispanic women. Journal of public health dentistry. Jul 25 2013.
6.
Chung LH, Gregorich SE, Armitage GC, Gonzalez-Vargas J, Adams SH. 
Sociodemographic disparities and behavioral factors in clinical oral health status 
during pregnancy. Community dentistry and oral epidemiology. Apr 
2014;42(2):151-159.
7.
Hwang SS, Smith VC, McCormick MC, Barfield WD. Racial/ethnic disparities in 
maternal oral health experiences in 10 states, pregnancy risk assessment 
monitoring system, 2004-2006. Maternal and child health journal. Aug 
2011;15(6):722-729.
8.
California HealthCare Foundation. Denti-Cal Facts and Figures. Oakland, CA: 
California HealthCare Foundation; 2010. 
9.
Dye BA, Mitnik GL, Iafolla TJ, Vargas CM. Trends in dental caries in children and 
adolescents according to poverty status in the United States from 1999 through 
2004 and from 2011 through 2014. J Am Dent Assoc. 2017 Aug;148(8):550-
565.e7. 
10.
Tanzer JM, Livingston J, Thompson AM. The microbiology of primary dental 
caries in humans. J Dent Educ. Oct 2001;65(10):1028-1037.
11.
Tinanoff N, O'Sullivan DM. Early childhood caries: overview and recent findings. 
Pediatr Dent. Jan-Feb 1997;19(1):12-16. 
12.
Kohler B, Andreen I, Jonsson B. The effect of caries-preventive measures in 
mothers on dental caries and the oral presence of the bacteria Streptococcus 
mutans and lactobacilli in their children. Arch Oral Biol. 1984;29(11):879-883.

CenteringPregnancy Oral Health Promotion (CPOP)
Version 2.03
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13.
Li Y, Caufield PW. The fidelity of initial acquisition of mutans streptococci by 
infants from their mothers. J Dent Res. Feb 1995;74(2):681-685.
14.
Berkowitz RJ. Mutans streptococci: acquisition and transmission. Pediatr Dent. 
Mar-Apr 2006;28(2):106-109; discussion 192-108.
15.
Thorild I, Lindau-Jonson B, Twetman S. Prevalence of salivary Streptococcus 
mutans in mothers and in their preschool children. Int J Paediatr Dent. Jan 
2002;12(1):2-7.
16.
Berkowitz RJ. Causes, treatment and prevention of early childhood caries: a 
microbiologic perspective. J Can Dent Assoc. May 2003;69(5):304-307.
17.
Kohler B, Andreen I. Influence of caries-preventive measures in mothers on 
cariogenic bacteria and caries experience in their children. Arch Oral Biol. Oct 
1994;39(10):907-911.
18.
da Silva Bastos Vde A, Freitas-Fernandes LB, Fidalgo TK, et al. Mother-to-child 
transmission of Streptococcus mutans: a systematic review and meta-analysis. 
Journal of dentistry. Feb 2015;43(2):181-191.
19.
Binks C, Duane B. Mother-to-child transmission of Streptococcus mutans. 
Evidence-based dentistry. Jun 2015;16(2):39-40.
20.
Oral Health Care During Pregnancy Expert Workgroup. Oral health care during 
pregnancy: a national consensus statement. Washington, DC: National Maternal 
and Child Oral Health Resource Center; 2012.
21.
IOM (Institue of Medicine) and NRC (National Research Council). Improving 
access to oral health care for vulnerable and underserved populations. 
Washington, DC: The National Academies Press; 2011.
22.
Ickovics JR, Kershaw TS, Westdahl C, et al. Group prenatal care and perinatal 
outcomes: a randomized controlled trial. Obstetrics and gynecology. Aug 
2007;110(2 Pt 1):330-339.
23.
Ickovics JR, Kershaw TS, Westdahl C, et al. Group prenatal care and preterm 
birth weight: results from a matched cohort study at public clinics. Obstetrics and 
gynecology. Nov 2003;102(5 Pt 1):1051-1057.
24.
Adams, SH, Gregorich SE, Rising, SS, Hutchison, M, Chung LH.  Integrating a  
nurse midwife-led oral health intervention into CenteringPregnancy® prenatal 
care: results of a pilot study. J Midwifery Women’s Health. 2017; 62(4):463-469
25.
Hayes RJ, Moulton LH. Cluster randomised trials. Boca Raton: CRC Press; 
2009.
26.
Caton JG, Polson AM. The interdental bleeding index: a simplified procedure for 
monitoring gingival health. The Compendium of continuing education in dentistry. 
Feb 1985;6(2):88, 90-82.

CenteringPregnancy Oral Health Promotion (CPOP)
Version 2.03
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27.
Adams SH, Hyde S, Gansky SA. Caregiver acceptability and preferences for 
early childhood caries preventive treatments for Hispanic children. J Public 
Health Dent. Fall 2009;69(4):217-224.
28.
Silness J, Loe H. Periodontal Disease in Pregnancy. Ii. Correlation between Oral 
Hygiene and Periodontal Condtion. Acta Odontol Scand. Feb 1964;22:121-135.
29.
Association of State and Territorial Dental Directors. Basic Screening Surveys: 
an approach to monitoring community oral health1999.
30.
Hoover CI, Newbrun E. Survival of bacteria from human dental plaque under 
various transport conditions. Journal of clinical microbiology. Sep 1977;6(3):212-
218.
31.
Mundorff SA, Eisenberg AD, Leverett DH, Espeland MA, Proskin HM. 
Correlations between numbers of microflora in plaque and saliva. Caries 
research. 1990;24(5):312-317.
32.
Steckler AB, Linnan L. Process evaluation for public health interventions and 
research. 1st ed. San Francisco, Calif.: Jossey-Bass; 2002.
33.
Vittinghoff E, Sen S, McCulloch CE. Sample size calculations for evaluating 
mediation. Stat Med. Feb 15 2009;28(4):541-557.
34.
Little RJA, Rubin DB. Statistical analysis with missing data. 2nd ed. Hoboken, 
N.J.: Wiley; 2002.
35.
Rubin DB. Multiple imputation for nonresponse in surveys. New York ;: Wiley; 
1987.
36.
Schafer JL. Analysis of incomplete multivariate data. Monographs on statistics 
and applied probability 72. London ; New York: Chapman & Hall,; 1997: 
https://ucsf.idm.oclc.org/login?url=http://uclibs.org/PID/31008.
37.
Rubin DB. Inference and missing data. Biometrika. 1976;63:581-592.
38.
D'Agostino RB, Jr. Propensity score methods for bias reduction in the 
comparison of a treatment to a non-randomized control group. Stat Med. Oct 15 
1998;17(19):2265-2281.
39.
Rosenbaum PR, Rubin DB. The central role of the propensity score in 
observational studies for causal effects. Biometrika. 1983;60:41-55.
40.
Rosenbaum PR, Rubin DB. Reducing bias in observational studies using 
subclassification on the propensity score. Journal of the American Statistical 
Association. 1984;79:516-524.
41.
Rubin DB. Using propensity scores to help design observational studies: 
application to the tobacco litigation. Health Serv Outcomes Res Methodol. 
2001;2:169-188.

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Version 2.03
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42.
Baron RM, Kenny DA. The moderator-mediator variable distinction in social 
psychological research: conceptual, strategic, and statistical considerations. J 
Pers Soc Psychol. Dec 1986;51(6):1173-1182.
43.
Li Y, Schneider JA, Bennett DA. Estimation of the mediation effect with a binary 
mediator. Stat Med. Aug 15 2007;26(18):3398-3414.
44.
Albert JM. Distribution-free mediation analysis for nonlinear models with 
confounding. Epidemiology. Nov 2012;23(6):879-888.