Interconception Health Intervention for Mothers in Pediatric Visits

Trial of a Pediatric Preconception Health Intervention

Journal Pre-proof

Cluster Randomized Trial of a Pre/Interconception Health Intervention for Mothers In Pediatric Visits Krishna K. Upadhya MD, MPH , Kevin J. Psoter MPA, PhD , Katherine A. Connor MD, MPH , Kamila B. Mistry PhD, MPH , Daniel J. Levy MD , Tina L. Cheng MD, MPH PII: DOI: Reference:

S1876-2859(19)30429-2 https://doi.org/10.1016/j.acap.2019.10.003 ACAP 1419

To appear in:

Academic Pediatrics

Received date: Accepted date:

28 February 2019 10 October 2019

Please cite this article as: Krishna K. Upadhya MD, MPH , Kevin J. Psoter MPA, PhD , Katherine A. Connor MD, MPH , Kamila B. Mistry PhD, MPH , Daniel J. Levy MD , Tina L. Cheng MD, MPH , Cluster Randomized Trial of a Pre/Interconception Health Intervention for Mothers In Pediatric Visits, Academic Pediatrics (2019), doi: https://doi.org/10.1016/j.acap.2019.10.003

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2019 by Academic Pediatric Association

Cluster Randomized Trial of a Pre/Interconception Health Intervention for Mothers In Pediatric Visits Short Title: Trial of a Pediatric Preconception Health Intervention Authors: Krishna K. Upadhya, MD, MPH1, 2 Kevin J. Psoter, MPA, PhD1 Katherine A. Connor, MD, MPH1 Kamila B. Mistry, PhD, MPH1, 4 Daniel J. Levy, MD1,5 Tina L. Cheng, MD, MPH1, 3 1 Department of Pediatrics, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Baltimore, MD 21287, USA; 2 Division of Adolescent and Young Adult Medicine, Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010 3 Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21287, USA 4 Office of Extramural Research, Education and Priority Populations, Agency for Healthcare Research and Quality, 5600 Fishers Lane, Rockville, MD 20857, USA 5 Child and Teen Wellness Center, 10085 Red Run Blvd Suite #201, Owings Mills, MD, 21117 Corresponding Author: Tina L. Cheng, MD, MPH Johns Hopkins University 1800 Orleans #8491 Baltimore, MD 21287 Phone: 410 955 5976; Email: [email protected] Email Addresses for Authors: Krishna K. Upadhya, MD, MPH: [email protected] Kevin J. Psoter, MPA, PhD: [email protected] Katherine A. Connor, MD, MPH: [email protected] Kamila B. Mistry, PhD, MPH: [email protected] Daniel J. Levy, MD: [email protected] Tina L. Cheng, MD, MPH: [email protected] Word Count: Abstract 312; Manuscript: 4133 Financial Disclosure: The authors have no financial relationships relevant to this article to disclose. Sources of Funding: We would like to acknowledge funding support for this project from Johns Hopkins HealthCare; Aetna, Abell and Straus Foundations; and The Zanvyl and Isabelle Krieger Fund. The funders/ sponsors had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The content is solely the

1

responsibility of the authors and do not necessarily represent the US Department of Health and Human Services or its component, the Agency for Healthcare Research and Quality or the funding agencies. Potential Conflicts of Interest: The authors have no conflicts of interest relevant to this article to disclose. Clinicaltrials.gov identifier: NCT02049554, tables, figures, CONSORT form Abbreviations: American Academy of Pediatrics (AAP), American College of Obstetrics and Gynecology (ACOG), Centers for Disease Control (CDC), Confidence Interval (CI), Odds Ratio (OR), Pregnancy Risk Assessment Monitoring Survey (PRAMS) Key Words: preconception health, interconception care, maternal health, What’s New Brief assessment and counseling regarding pre/interconception health needs of mothers in pediatric primary care visits are feasible and improve pre/interconception health behaviors. Delivery of pre/interconception care in pediatric visits has the potential to promote positive birth outcomes in subsequent pregnancies. Contributors’ Statements: Krishna Upadhya conceptualized and designed the study, designed the data collection instruments, coordinated and supervised data collection at the research site drafted the initial manuscript, reviewed and revised each draft of the manuscript and approved the final manuscript as submitted. Kevin Psoter analyzed the data, reviewed and revised each draft of the manuscript and approved the final manuscript as submitted. Katherine Connor coordinated and supervised data collection at the research site, reviewed and revised each draft of the manuscript and approved the final manuscript as submitted. Kamila Mistry designed the data collection instruments and reviewed and revised each draft of the manuscript and approved the final manuscript as submitted. Daniel Levy contributed to acquisition of data, critically reviewed the manuscript, and approved the final manuscript as submitted. Tina Cheng conceptualized and designed the study, designed the data collection instruments, reviewed and revised each draft of the manuscript and approved the final manuscript as submitted.

2

Abstract Objective: Recognizing that pediatric primary care focuses on family health and is an important location of contact for women of childbearing age, this project assessed the effectiveness of a pre/interconception women’s health intervention delivered during pediatric primary care using a cluster randomized trial. Methods: Pediatric clinicians were randomized to a screening and brief educational intervention group or usual care comparison group. Intervention group clinicians received training on pre/interconception care, including recommended counseling and referral resources for needs identified. Women presenting to primary care with their child <12 months were enrolled and assigned to the group corresponding to the assignment of their child’s clinician. Mothers seen by clinicians in the intervention group completed a pre/interconception health screening tool and discussed results with their child’s clinician during the visit. These mothers were compared to mothers seen by comparison group clinicians who did not receive the screening tool or clinician discussion. All enrolled mothers (Intervention and Comparison) received written preconception health information and a 90 day supply of multivitamins. Primary outcomes at 6 and 12 months post enrollment included contraception use, pregnancy, and access to and use of preventive health care. Secondary outcomes included daily folic acid supplementation, smoking and substance use. Results: 415 women were enrolled and those who had at least one follow-up assessment were included in the analysis (n= 383). There was no significant effect of the intervention on contraceptive use, pregnancy incidence, or use of preventive care. Assignment to the intervention increased the odds of daily folic acid use [OR 1.82, 95% CI 1.25, 2.63] during follow-up. Intervention mothers were less likely to smoke at 6, but not 12 months. Conclusions: Pediatric visits are an opportune location for addressing maternal health and this intervention demonstrated feasibility and improved outcomes for some but not all outcomes Attention to maternal health needs across pediatric visits during infancy may be important for maintaining positive pre/interconception health behaviors.

3

INTRODUCTION Even with recent declines, the US rate of infant mortality (5.9/1,000 live births) remains unacceptably high. Racal/ethnic disparities in infant mortality are also persistent; in 2015 nonHispanic black infant mortality was over twice the rate of that for non-Hispanic white infants (1). Despite improvements in access to prenatal care, the “Back to Sleep” campaign and scientific and clinical advancements, the United States ranks 30th among the 41 nations of the Organization for Economic Cooperation and Development in infant mortality (2). New approaches are needed to reach the Healthy People 2020 goal of reducing infant mortality by 10%. There is growing recognition that interventions to reduce infant mortality and improve child health must go beyond the pre- and peri-natal periods to also focus on the preconception health of women (3). Critical fetal development occurs in the earliest weeks after conception and often before a woman is aware of her pregnancy. With nearly half of all pregnancies in the US considered unintended, the prenatal period may be too late to address many maternal and fetal risks (4). Maternal health (e.g. diabetes, cardiovascular diseases, depression) and behaviors (e.g. smoking, drug use, nutrition) impact birth, childhood and adult health outcomes. The story of folic acid supplementation is a powerful example of how a preconception intervention can influence child health. A folate educational campaign and fortification of grains led to a 26% drop in the rate of neural tube defects (5,6). Reducing unintended pregnancy and improving preconception health serve as critical steps in reducing disparities, improving women’s health and their birth outcomes. The American Academy of Pediatrics (AAP) and American College of Obstetrics and Gynecology (ACOG) have advocated for women to receive counseling on optimizing health before pregnancy at all health care encounters during the reproductive years and have provided

4

guidelines for the content of that counseling (7,8). The Institute of Medicine report on “Clinical Preventive Services for Women” recommended annual well-women visits including preconception care (9) and Healthy People 2020 includes a section of objectives on preconception health behaviors (10) with domains of preconception healthcare and evidence for interventions outlined by a Centers for Disease Control and Prevention Select Panel (11). Despite these recommendations, population-based data found that less than one-third of women with a recent live birth reported receiving preconception counseling (12). Pediatric clinicians interface with women of child-bearing age, preconceptional adolescents and mothers between pregnancies (interconception, a subset of preconception), possibly more than other clinicians in the healthcare system (11,13). A survey of women age 1844 found that only 55% had seen an obstetrician-gynecologist in the previous year; low-income women and women in poor health were less likely to have had a visit (14) and often lack insurance (15). By contrast, virtually all young children have had a well visit in the past year (96.8% of children 0-4 years) usually accompanied by their mother (16). Pediatric visits are an access point for pre/interconception screening and providing or referring to needed services. Offering selected women’s health care services at the same site, same time and with the same trusted clinician as their child can decrease barriers to care, increase communication and has the potential to improve the health of the woman, their child, family and future children. To evaluate this approach empirically, we conducted a cluster randomized trial to determine whether a brief intervention within Pediatric primary care with mothers of young children increases positive interconception health behaviors compared to education materials alone.

5

PATIENTS AND METHODS The design of this cluster randomized trial has been previously described (17). Briefly, four pediatric primary care practices in the Baltimore, Maryland area participated in this trial between October 2013 and March 2015. Within each practice site clinicians were assigned to either the intervention or usual care group using a random number generator. Mothers who agreed to participate were then enrolled in their child’s clinician study arm. Randomization by clinician rather than patient was performed to avoid clinician contamination across the two groups. Mothers presenting with their child <12 months of age for a well care visit to one of the four participating practices were approached for participation. Eligibility criteria included: biologic mothers, English or Spanish-speaking, and mental and physical capacity to participate in the study assessments. Women known to be pregnant at the time of the visit were excluded. The study was approved by the Institutional Review Board at Johns Hopkins School of Medicine and registered as a clinical trial (Clinicaltrials.gov identifier: NCT02049554). Study materials were reviewed by one clinic’s Community Advisory Board. Study Procedures A total of 45 pediatric clinicians (physician or nurse practitioner) were randomized. After randomization, study investigators (K.U. or K.C.) visited each practice to train clinicians assigned to the intervention. Meetings with each clinician group lasted 45-60 minutes and included an overview of pre/interconception health, introduction to the intervention screening tool, and specific recommendations for counseling based on evidence and CDC recommendations (11) and local referral resources to address risks identified on the questionnaire. Clinicians were trained to emphasize the importance of the health of mothers for

6

themselves and their children, planning future pregnancy with optimal interconceptional interval of >18 months, and multivitamin intake. Clinicians were urged to discuss contraceptive options and encouraged to provide contraception or refer. Clinicians had the opportunity to ask questions and were provided with reference materials. Research assistants approached mothers in the clinic to explain the study and assess their eligibility and interest in participation. Informed consent was obtained and a baseline survey completed during the visit. Outcome data were collected by phone 6 months and 12 months later by a trained research assistant who was blind to study group assignment. Participants were compensated for completion of each assessment with at $25 gift card. Intervention and Comparison Conditions Participants in the Comparison group received the Centers of Disease Control and Prevention (CDC) preconception women’s health booklet entitled “Show Your Love, Steps to a Healthier Me,” a list of relevant local resources, and a 90 day supply of vitamins containing 400 mcg folic. In addition to those items, participants in the intervention group completed a 15-item Women’s Health Screening Tool that was then given to the pediatric clinician for review and feedback during the child’s clinic visit. The screening tool was developed by inclusion of components recommended for PCC (11) with items from national health care and epidemiologic surveys [e.g. Pregnancy Risk Assessment Monitoring System (PRAMS), National Survey of Family Growth (NSFG), and National Health Interview Survey (NHIS)]. Exit interviews were conducted with a sample of mothers in the intervention group. For concerns identified in the screener (no health insurance, no routine healthcare clinician, no contraception and does not want to be pregnant, smoking, use of illicit drugs, depressive symptoms, partner abuse) mothers

7

reported that clinicians discussed these issues in the visit 84-100% of the time depending on the identified concern. Study staff assisted intervention clinicians and participants with connection to specific resources for all needs identified on the screening tool, for example identification of a primary care site, family planning clinics, mental health services, smoking cessation hotlines, and domestic violence shelters. Attempts were also made to contact intervention participants by phone 2-4 weeks after their visit to assist with follow-up and to reinforce messages tailored to the mother’s screener-identified needs. Measures All baseline and outcome measures were assessed by maternal self-report. Survey development was guided by review of the literature on preconception women’s health and, where available, items from national health care and epidemiologic surveys noted above were used verbatim. To ensure the screening tool and outcome questions targeted relevant constructs and were acceptable to the target population, development included review by the Community Advisory Board. The interview instrument underwent rigorous one-on-one pretesting including cognitive interviews probing how respondents understood and interpreted the study questions. This was followed by pilot testing the study process and completion of the interview under study conditions. Outcome Variables The exposure of interest was study group assignment defined as Intervention or Comparison group. The primary outcomes were contraceptive use, pregnancy and access to/use of preventive health care. We assessed contraceptive use with questions from the National

8

Survey of Family Growth. Participants not currently pregnant or desiring pregnancy were asked if they or their partner were using a method to prevent pregnancy at the time of the 6 and 12 month interviews and, if so, to specify the method used from a list which included barrier, hormonal, intrauterine, and other methods. Based on responses, participants were grouped as using sterilization, “highly effective” reversible methods (including hormonal methods and IUDs), or other method (e.g. condoms, withdrawal) (18). Participants were asked whether they were currently pregnant or had been pregnant since the prior survey. To measure access to preventive care, National Health Interview Survey questions on being insured, having a personal doctor, and having a recent check-up were utilized. We also asked about visits to discuss contraception since the prior interview. Secondary outcomes: Daily folic acid, multivitamin or prenatal vitamin use (hereafter referred to as “vitamin use”) was assessed by response to the question taken from the Pregnancy Risk Assessment Monitoring Survey (PRAMS): “Currently, how many times a week do you take a multivitamin, a prenatal vitamin, or a folic acid vitamin?” Response categories included: (a) “I don’t take a multivitamin, prenatal vitamin or folic acid vitamin at all,” (b) “1 to 3 times a week,” (c) “4 to 6 times a week,” (d) “Every day of the week.” For analysis, responses were dichotomized to indicate daily versus not daily intake for consistency with national guidelines and prior studies (19,20). Current tobacco use was assessed by asking participants to report the number of cigarettes they used daily and answers were dichotomized into any use vs. none. Excess alcohol use was defined by report of having 5 or more alcoholic beverages in a couple of hours since prior interview. Marijuana use was defined as any use reported since prior interview. Covariates

9

Factors known to be associated with pre/interconception health factors were also collected including mother’s age at enrollment, race, income, insurance type, parity, time since delivery (child age at enrollment), and intendedness of the index pregnancy Sample Size and Data Analysis We planned our sample size on the primary outcome of interest, use of highly effective contraception (sterilization, IUD, implant, or hormonal method). Based on prior work with the target population we estimated a baseline usage of 60% and a sample size of 160 per arm in order to detect a 20% increase with 80% power and a two tailed p value of 0.05. Using a conservative estimate of design effect (DEFF) to adjust the variance of anticipated parameter estimates and account for the dependency in the data (21, 22) in the clustered design and expecting some attrition and loss to follow-up we increased our goal sample size to 200 per arm. The unit of analysis was the individual. Statistical analyses included all individuals who were enrolled in the study, and had data collected at 6 and/or 12 month follow-up time points. Baseline characteristics and behaviors, and 6 and 12 month outcomes were compared in intent to treat analysis between individuals who were randomized to the intervention and comparison groups using student t tests with unequal variances and Chi squared or Fisher exact tests for continuous and categorical variables, respectively. To evaluate the effect of the intervention over time on selected outcomes, generalized linear and mixed models with a binomial distribution and a logit link function were utilized. Initially, unadjusted analyses were performed that included fixed effects terms for the intervention (yes/no), time (baseline, 6, 12 months) and an intervention by time interaction term, which represented the difference in change in outcomes between the two groups. Next,

10

multivariable regression, adjusting for mother and child’s age, race, income, insurance status, parity, time since delivery (child age at enrollment), and intendedness of the index pregnancy, was used to evaluate the potential effect of individual-level characteristics for each of the intervention-outcome associations. Finally, to account for the variability between clusters (providers) inherent in the clustered trial design, a random effect term for each provider was included in each multivariable model. Results of regression models are presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). A P<0.05 was considered statistically significant. All analyses were conducted using STATA Version 14 software (College Station, TX). RESULTS Figure 1 presents the study recruitment and those completing follow-up at 6 and 12 months. Of the 453 eligible women who were approached, 8% (n=38) refused participation. A total of 415 mothers were enrolled with 197 randomized to the intervention group and 218 to the Comparison group; 352 (85%) completed 6 month assessments and 361 (88%) completed 12 month assessments. Participants who had follow-up data for at least one time point (n=383) were included in the analyses. Demographic characteristics of participants lost to follow-up were similar to those that completed at least one follow-up (data not presented). Characteristics of mothers in both groups were well balanced (Table 1). Pre/interconception health behaviors did not differ between groups at baseline (Table 2) with the exception of daily vitamin use which was more prevalent in the Comparison group (40.7% vs. 26.3%, p=0.003). Nearly all intervention and Comparison participants (96.3% and 98.0%) reported not wanting to be pregnant in the next 6 months, and approximately 60% of

11

those reported sterilization or highly effective contraceptive use at baseline. They were then asked “Are you or your partner currently doing anything to keep you from getting pregnant now?” 89.4% answered “yes.” Among the minority stating “no,” (N= 40) top reasons for not preventing pregnancy included 26% answering “I don't mind if I get pregnant” and 22% answering “I am having infrequent sex.” Table 3 summarizes the outcomes at 6 and 12 months for participants randomized to the intervention and control conditions. There was no statistically significant difference in report of pregnancy, desire for pregnancy or contraceptive use between groups at 6 or 12 months. Report of daily vitamin use increased within the intervention group to 43.6% (from 26.3%) and 39.8% at 6 and 12 months respectively. A lower proportion of Intervention compared with Comparison group participants reported current tobacco use at 6 months (12.9% vs. 21.2%, p =.041), however there was no difference in prevalence of tobacco use between groups at 12 month follow-up. In follow-up, 93.2% and 90.0% reported not being pregnant or trying to have another baby in the next 6 months at the 6 and 12 month interviews respectively. When asked “Are you or your partner currently doing anything to keep you from getting pregnant now?” 88.9% and 87.1% reported "yes" at the 6 and 12 month interviews, respectively. As noted in Table 3 only about half were using highly effective methods of contraception including hormonal methods, IUDs or sterilization. Table 4 shows results of regression analyses for the effect of the intervention on change in outcomes of interest during follow-up. After adjustment for baseline characteristics and the clustered study design, there was no statistically significant effect of the intervention on report of pregnancy, contraceptive use, or use of preventive care during follow-up. Assignment to the Intervention group did increase the odds of daily folic acid supplement use during follow-up [OR

12

1.78, 95% CI 1.22, 2.59]. Intervention group participants were less likely to be insured during follow-up compared with Comparison group participants [OR 0.23, 95% CI 0.07, 0.71]. Finally, Intervention group participants had lower odds of binge drinking during follow-up [OR 0.09, 95% CI 0.01, 0.77]. Change in insurance status was also added to the model as a time varying covariate. When we performed this analysis the results were nearly identical to those that did not include adjustment for change in insurance status. DISCUSSION Optimizing women’s health, including before and between pregnancies, remains a critical public health objective. While components of pre/interconception care, including contraception to facilitate pregnancy planning and birth spacing, cessation of smoking and other substance use, and folic acid supplementation have strong evidence behind them, surveillance data reported by women who have delivered children suggest that additional interventions are needed to ensure delivery of pre/interconception care. Our study demonstrates that pediatric primary care clinics serve women with interconception health needs and can be a feasible and effective delivery site for care. Our intervention did appear to have effects at the first follow-up on reducing tobacco use, however that effect was not statistically significant at 12 month follow-up consistent with other studies showing fading of intervention impact over time and postpartum relapse for behaviors such as smoking (23). The smoking intervention involved screening for past tobacco use, reinforcement of the benefits of cessation for the health of current and future children, assessment of maintenance of cessation or willingness to quit, and direct referral to a stop smoking quitline. It is possible that multiple visits, as opposed to at one visit as was the focus of our intervention, may be important to maintain positive interconception health behaviors. Eight pediatric visits are

13

recommended during the first year of life, including four where screening for maternal depression is recommended (24). Although screening for tobacco use and advising cessation is not specifically included in the infant periodicity schedule, research has suggested that even brief advice to quit from physicians can increase the likelihood of cessation by 1-3% (25). Given the known harms to children from second hand smoke and to pregnancies from tobacco use, adding screening and brief intervention during multiple visits could have a significant impact on child health. The outcomes at 12 months support our previously published findings from the 6 month follow-up (9) and indicate that our intervention effect on daily use of folic acid supplementation persisted beyond 6 months. While we did find a statistically significant reduction in report of binge drinking among intervention compared with comparison group participants, the small numbers reporting this behavior limits our confidence in the clinical significance of this finding. A significant proportion of women who participated in the study reported not using a highly effective contraceptive method in spite of stating they did not desire pregnancy in the near term, representing a potential opportunity for pediatric clinicians to facilitate improved contraceptive use. Most frequent reasons for not using contraception included “I don't mind if I get pregnant” and “I am having infrequent sex.” Unfortunately, our one-time intervention emphasizing the recommendation of an interpregnancy interval > 18 months (26) did not show a significant effect on contraceptive use during our study period. Additional strategies to encourage effective contraceptive use must address the ambivalence of some mothers, preparation for when they have a new partner, and greater emphasis on the importance of a longer interpregnancy interval for their health and the health of their current and future children. The training provided to our intervention clinicians included tools for contraceptive counseling

14

and referral sites for free or sliding scale contraceptive care. Clinicians were also encouraged to provide prescriptions for contraception if possible though few did. National surveys have found that despite Bright Futures’ recommendations for child health clinicians to address caregiver family planning during pediatric visits, documented counseling is rare (27). Though exit interviews confirmed that clinicians did address the issue in our study, the lack of effect on women’s contraceptive use may be an indication that greater efforts and resources beyond recommended counseling messages and referral resources will be needed to have women’s contraceptive needs addressed outside of their own medical homes. A recent study of women attending family medicine clinics with their 12 or 24 month olds for well child care suggested that addressing maternal family planning needs is less likely when the mother and child see separate clinicians, even when the family medicine physician providing care for the child also treats adults (28). Initiatives to encourage primary care clinicians to routinely assess women’s reproductive health needs including the One Key Question practice and technology assistance are first steps (29,30). Further interventions specifically focused on encouraging pediatric clinicians to routinely ask about, provide or facilitate access to family planning services for women in a patient-centered approach should be explored. Access to women’s health services within pediatric primary care, co-located or easily available in other locations is also critical to address reproductive empowerment and pre/interconception women’s health. We recognize the power of the trusted clinician and wished to leverage this relationship in team-based primary care. It is well-documented that clinicians have limited time to cover all recommended health supervision topics. In designing the intervention we were concerned with the feasibility and impact of a clinician-only intervention and thus augmented the interventions

15

with tools including the screener, handouts, referral resources, vitamins and having study staff reinforce messages from the clinician. If mothers reported depression or safety concerns these were directly addressed by clinicians. Study staff did attempt to call mothers in the intervention group 2-4 weeks after their visit to reinforce the clinician discussion reaching 46% of mothers. To replicate this intervention it would be necessary to utilize these tools and involve other primary care team members to achieve expected impact. Additional reinforcement at later visits may also augment behavior change. There have been few published studies on interventions addressing comprehensive preconception care in primary care (31). This is the first known intervention study that took advantage of pediatric primary care as a location of contact to reach mothers for interconception care. Pediatric clinicians have long recognized the importance of family health, parental health behaviors and prevention in ensuring child health and with training and tools were willing to address interconception women’s health in this study. In post-intervention debriefing some participating intervention clinicians commented that this intervention influenced their counseling with families and have continued using the screener or selected questions from the screener. A past survey of Pediatric primary care physicians found that the majority endorsed the relevance of parental health to child health, particularly for issues with an established evidence base, many fewer felt responsible or had the capacity to address parental health issues without incentives to do so (32). Pediatric primary care clinicians are well-positioned to proactively address pre/interconception care with women and families prior to, during, and after pregnancy. While this is an extension of the family health orientation in most pediatric practices, it is in line with the prevention and life course focus of pediatrics. However, training and reimbursement are

16

needed. This study demonstrates the potential for improved outcomes for the family and future children. Our findings must be considered in light of some limitations. The study was conducted in four pediatric primary care practices serving large proportions of low income families and results may not be generalizable to other practices and populations. Second, our outcomes were based on self-report which may be subject to recall and/or social desirability bias. While the decision to randomize clinicians as opposed to mothers likely reduced the risk of contamination, we cannot rule out contamination between clinicians and potential bias related to differences in clinician panels. Significantly more uninsured mothers in the intervention group compared to the comparison group at 12 months might suggest a higher risk intervention group. Unbalanced randomization would have reduced power to find differences. In addition, program impact and ability to detect effects likely was diminished as a result of the comparison group receiving some education about maternal health and folate vitamins which are beyond usual care in pediatric practice. Finally, our analyses addressed program effectiveness, not efficacy, as we provided training and recommended counseling to pediatric clinicians but relied on them to incorporate that training into the visit. This more closely approximates real world implementation, but may dilute the intervention impact. This study had many features of a pragmatic trial with positive and negative results on measured outcomes. Pragmatic trials are designed to evaluate the effectiveness of interventions in real-life routine practice conditions and fill an important gap by more fully accounting for the interplay and tradeoffs between research design, feasibility, stakeholder acceptability and generalizability. Pragmatic trials often have complex interventions, sometimes consisting of several interacting components, and may involve the skills and experience of a team of health

17

care professionals in actual practice (33). This study demonstrates the feasibility and acceptability of an interconception women’s health intervention in primary care and proof-ofconcept for some outcomes. It offers important information about dose of the intervention, areas of refinement and potential value in clinical practice to achieve improved family outcomes. CONCLUSION This intervention trial illustrated that brief assessment and counseling regarding pre/interconception health needs of mothers in pediatric primary care visits was feasible and improved interconception health behaviors of maternal smoking and folate supplementation in the short term, but did not impact family planning outcomes. Delivery of pre/interconception care in pediatric visits has the potential to promote positive women’s health and birth outcomes in subsequent pregnancies. Future work should explore the impact of addressing maternal health needs at multiple visits across infancy and more targeted approaches to addressing contraceptive needs.

18

Table 1: Demographic Characteristics of patients with baseline and at least one follow-up visit (either 6 month, 12 months or both), by intervention status

Age, mean (SD) Race, n (%) White Black Other Education level, n (%) < High school High school Some college or post high school Marital status, n (%) Married/ cohabitation Other Family Income, n (%) <20,000 20,000-50,000 >50,000 Don’t know Index child age months, mean (SD) Currently insured, n (%) Total number of pregnancies, mean (SD) Total number of live births, n (%) 1 2 3 >3 Trying to get pregnant at time of index pregnancy, n (%) Prior preterm labor, n (%) Prior low birth weight, n (%)

Comparison Group (n=204) 26.5 (6.0)

Intervention Group (n=179) 26.5 (6.3)

17 (8.3) 169 (82.8) 18 (8.8)

11 (6.2) 157 (87.7) 11 (6.2)

48 (23.5) 66 (32.4) 90 (44.1)

45 (25.1) 64 (35.8) 70 (39.1)

45 (22.1) 159 (77.9)

26 (14.5) 153 (85.5)

p value

0.960 0.585

0.607

0.058

0.384 101 (49.5) 45 (22.1) 38 (18.6) 20 (9.8) 4.8 (3.6) 195 (95.6) 2.8 (2.0)

93 (52.0) 43 (24.0) 22 (12.3) 21 (11.7) 5.2 (3.5) 172 (96.1) 2.8 (2.0)

101 (49.5%) 49 (24.0) 26 (12.8) 28 (13.7) 52 (25.6)

74 (41.3) 54 (30.2) 26 (14.5) 25 (14.0) 42 (23.5)

0.626

57 (27.9) 14 (6.9)

40 (22.4) 7 (3.9)

0.239 0.205

0.280 0.807 0.701 0.398

Note- P values reflect results of Student t tests with unequal variances comparing continuous variables and Chi squared tests comparing categorical variables

19

Table 2: Comparison of baseline behaviors of subjects who completed 6 and or 12 month followup, by intervention status

Contraceptive Method (n, %)** Sterilization Hormonal method or IUD Other Pregnant since delivery (n, %) Currently pregnant or trying (n, %) Visited clinician for a check-up since pregnancy (n, %) Visited clinician to discuss contraception since pregnancy (n, %) Has a personal doctor (n, %) Currently have insurance (n, %) Daily use of vitamin with folic acid (n, %) Current Tobacco Use (n, %) Binge drinking since birth (n, %) Use of marijuana since birth (n, %)

Comparison Group (n=204)

Intervention Group (n=179)

P value*

17 (9.1) 87 (46.5) 83 (44.4) 6 (2.9) 7 (3.5) 107 (52.5)

13 (8.2) 86(54.1) 60 (37.7) 5 (2.8) 3 (1.7) 101 (56.7)

1.000 0.347 0.401

165 (80.9)

135 (75.4)

0.195

141 (69.1) 195 (95.6) 83 (40.7)

123 (68.7) 172 (96.1) 47 (26.3)

0.932 0.807 0.003

36 (17.7) 4 (2.0) 16 (7.8)

29 (16.2) 7 (3.9) 15 (8.4)

0.707 0.360 0.848

0.371

* P values reflect results of Chi squared or Fisher exact tests. ** Percent of total participants using contraception and not trying to get pregnant

20

Table 3: Comparison of 6 and 12-month follow-up behaviors of subjects who completed 6 and/or 12 month follow-up, by intervention status 6 month, N=352 Control Intervention Group Group (n=189) (n=163) Current contraceptive method (n, %)** Sterilization Hormonal method or IUD Other Pregnant since baseline (n, %) Currently pregnant or trying (n, %) Visited clinician for a checkup since prior interview (n, %) Visited clinician to discuss contraception since prior interview (n, %) Personal doctor (n, %) Currently insured (n, %) Daily use of vitamin with folic acid (n, %) Current Tobacco Use (n, %) Binge drinking since prior interview (n, %) Use of marijuana since prior interview (n, %)

P value 0.917

12 month, N=361 Control Intervention P Group Group value (n=193) (n=167) 0.715

13 (7.3) 76(42.9)

11 (7.2) 62 (40.8)

17 (8.9) 89 (46.4)

14 (8.5) 70 (42.4)

88 (49.7) 18 (9.5) 5 (2.7)

79 (52.0) 15 (9.2) 3 (1.8)

0.918 0.729

86 (44.8) 26 (13.4) 20 (10.4)

81 (42.1) 25 (15.0) 15 (9.0)

0.872 0.659

98 (51.9)

92 (56.8)

0.355

146 (75.3)

120 (71.9)

0.464

152 (80.4)

123 (75.5)

0.261

106 (54.6)

95 (56.9)

0.668

130 (68.8) 180 (95.2) 79 (41.8)

114 (69.9) 156 (95.7) 71 (43.6)

0.815 0.834 0.739

151 (77.8) 186 (95.9) 69 (35.6)

128 (76.7) 149 (89.8) 66 (39.8)

0.788 0.018 0.413

40 (21.2) 3 (1.6)

21 (12.9) 2 (1.2)

0.041 0.776

30 (15.5) 3 (1.6)

26 (15.7) 1 (0.6)

0.975 0.628

7 (3.7)

10 (6.1)

0.289

10 (5.2)

4 (2.4)

0.274

* P values reflect results of Chi squared or Fisher exact tests. ** Percent of total participants using contraception

21

Figure 1. Project Recruitment Yield Assessed for eligibility (n=749)

Excluded (n=334):  Not meeting inclusion criteria (n=103)  Declined to participate (n= 38)  Not Approached: (n= 193)

Assigned to Study Group (n= 415):

Total allocated to Intervention (n=197):

Total allocated to Comparison (n=218)

 Received screener intervention including 2 week follow up calls (n=196)

6 Month Follow-Up Intervention Group surveys completed (n = 163) [82.7%] Phone disconnected at time of 6 month (n= 9) Lost to follow-up (unavailable/does not call back) (n=16) Discontinued intervention (refused) (n= 9)

Comparison Group surveys completed (n = 189) [86.7%] Phone disconnected at time of 6 month (n=10) Lost to follow-up (unavailable/Incomplete) (n=15) Discontinued intervention (refused) (n= 4)

12 Month Follow-Up Intervention group surveys completed (n = 167) [84.8%] Phone disconnected at time of 12 month (n=5) Lost to follow-up (unable to contact) (n=17) Discontinued intervention (refused) (n=8)

Comparison group surveys completed (n = 193) [88.5%] Phone disconnected at time of 12 month (n=2) Lost to follow-up (unable to contact) (n=15) Discontinued intervention (refused) (n=8)

22

Figure 2:

*Highly effective contraception: sterilization, IUD, hormonal methods.

23

Table 4: Logistic regression analyses evaluating the association between intervention status (control vs. intervention group) and selected behavioral outcomes amongst women completing at least one follow-up visit (either 6 month, 12 months or both) Unadjusted Odds Ratio (95% Confidence Interval)

Adjusted Odds Ratio (95% Confidence Interval)*

Using Sterilization/Hormonal/IUD vs. other Using Sterilization/Hormonal/IUD/ condoms/withdrawal vs. other Pregnant since baseline

0.69 (0.44, 1.10)

Currently pregnant or trying to get pregnant Had a check-up since baseline

1.04 (0.25, 4.35)

Had a contraceptive discussion with clinician since baseline Personal doctor

1.26 (0.89, 1.77)

Currently insured

0.40 (0.19, 0.86)

Daily use of vitamin with folic acid

1.85 (1.25, 2.73)

Current Tobacco Use

0.39 (0.16, 0.95)

Binge Drinking since baseline

0.32 (0.09, 1.23)

Use of marijuana since baseline

0.59 (0.24, 1.43)

0.71 (0.45, 1.12) 0.71 (0.45, 1.14) 1.21 (0.60, 2.44) 0.85 (0.21, 3.43) 0.78 (0.54, 1.12) 1.33 (0.93, 1.88) 0.93 (0.61, 1.40) 0.41 (0.19, 0.89) 1.81 (1.23, 2.67) 0.54 (0.24, 1.20) 0.32 (0.08, 1.35) 0.55 (0.22, 1.41)

0.69 (0.44, 1.10) 1.16 (0.58, 2.33)

0.80 (0.56, 1.15)

0.88 (0.59, 1.33)

Design-based Adjustment Odds Ratio (95% Confidence Interval)** 0.71 (0.47, 1.08) 0.72 (0.46, 1.12) 1.33 (0.48, 3.71) 0.84 (0.06, 12.08) 0.78 (0.55, 1.11) 1.31 (0.93, 1.86) 0.93 (0.62, 1.39) 0.23 (0.07, 0.71) 1.78 (1.22, 2.59) 0.35 (0.09, 1.41) 0.09 (0.01, 0.77) 0.29 (0.08, 1.00)

* Each model is adjusted for mother’s age at enrollment, race, income, insurance status, parity, time since delivery (child age at enrollment), and intendedness of the index pregnancy ** Each model includes all covariates from the adjusted model, in addition to, a random effect term to account for participants seen by each provider

24

References

1. Centers for Disease Control and Prevention. [Internet] Infant Mortality 2015. Available at: https://www.cdc.gov/reproductivehealth/maternalinfanthealth/infantmortality.htm (Accessed February 13, 2018). 2. Infant mortality rates (indicator). [Internet].: Organisation for Economic Co-Operation and Development; 2017 [cited June 22, 2017]. Available from: https://data.oecd.org/healthstat/infantmortality-rates.htm. 3. Centers for Disease Control and Prevention, Recommendations to improve preconception health and health care—United States: A report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on Preconception Care. MMWR 2006;55(RR06):1-23. 4. Finer LB, Zolna MR. Declines in Unintended Pregnancy in the United States, 2008-2011. N Engl J Med. 2016 Mar 3;374(9):843-52. 5. Howse JL. Marching forward: action steps to optimize the health of women and babies. Women’s Health Issues 2008;18S:S10-S12. 6. De-Regil LM, Fernández-Gaxiola AC, Dowswell T, Peña-Rosas JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD007950. 7. ACOG Committee on Gynecologic Practice. ACOG Committee Opinion: The Importance of Preconception Care in the Continuum of Women’s Health Care. Obstetrics & Gynecology. 2005;106:665-6. 8. American Academy of Pediatrics. American College of Obstetricians and Gynecologists Guidelines for Perinatal Care. 6th ed. American Academy of Pediatrics, editor. Elk Grove Village, IL: American College of Obstetricians and Gynecologists; 2007. 9. Board on Population Health and Public Health Practice, Institute of Medicine. Clinical Preventive Services for Women: Closing the Gaps. Washington DC, The National Academies Press, 2011. 10. U.S. Department of Health and Human Services. Office of Disease Prevention and Health Promotion Healthy People 2020. [Internet].:Washington, DC, Maternal, Infant, and Child Health Objectives. [cited July 4, 2019]. http://healthypeople.gov/2020/topicsobjectives2020/objectiveslist.aspx?topicId=26. 11. Jack BW, Atrash H, Coonrod DV, Moos M, O’Donnell J, Johnson K. The clinical content of preconception care: An overview and preparation of this supplement. Am J Obstetrics Gynecology. 2008;S266-279.

25

12. Williams L, Zapata LB, D’Angelo DV, Harrison L, Morrow B. Associations between preconception counseling and maternal behaviors before and during pregnancy. Matern Child Health J 2012;16(9):1854-61. 13. Wise PH. Transforming preconceptional, prenatal, and interconceptional care into a comprehensive commitment to women’s health. Womens Health Issues. 2008;18S:S13-8. 14. Salganicoff A, Ranji U, Wyn R. Women and health care: a national profile: key findings from the Kaiser Women’s Health Survey. Menlo Park, CA.: Kaiser Family Foundation; 2005. 15. Clapp MA, James KE, Kaimal AJ, Daw JR. Preconception coverage before and after the Affordable Care Act Medicaid expansions. Obstr Gynec. 2018;132:1394-400. 16. Bloom B, Cohen RA, Freeman G. Summary health statistics for U.S. children: National Health Interview Survey, 2009. National Center for Health Statistics. 2010;10(247). 17. Chilukuri N, Cheng TL, Psoter KJ, Mistry KB, Connor KA, Levy DJ, et al. Effectiveness of a Pediatric Primary Care Intervention to Increase Maternal Folate Use: Results from a Cluster Randomized Controlled Trial. J Pediatr. 2018 Jan;192:247,252.e1. 18. Centers for Disease Control and Prevention. [Internet] Effectiveness of Family Planning Methods. [cited February 15, 2018]. Available at: https://www.cdc.gov/reproductivehealth/contraception/unintendedpregnancy/pdf/Contraceptive_ methods_508.pdf. 19. Maternal, Infant, and Child Health [Internet]. Washington, D.C.: U.S. Department of Health and Human Services; 2017 [cited June 22, 2017]. Available from: https://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-childhealth/objectives. 20. PRAMStat | Reproductive Health | [Internet]. Atlanta, GA: U.S. Centers for Disease Control and Prevention; January 26, 2017 [updated 2017; cited June 22, 2017]. Available from: http://www.cdc.gov/prams/pramstat/. 21. Donner A, Birkett N, Buck C. Randomization by cluster: sample size requirements and analysis. Am J Epidemiol. 1981;114:906-14. 22. Heo MS, Kim YM, Xue XN, Kim MY. Sample size requirement to detect an intervention effect at the end of follow-up in a longitudinal cluster randomized trial. Stat Med. 2010;29:38290. 23. Levine MD, Cheng Y, Marcus MD, Kalarchian MA, Emery RL. Preventing Postpartum Smoking Relapse: A Randomized Clinical Trial. JAMA Intern Med. 2016 Apr;176(4):443-52. 24. Recommendations for Pediatric Preventive Healthcare [Internet]. Elk Grove Village: American Academy of Pediatrics; 2017 [cited June 21, 2017]. Available from: https://www.aap.org/en-us/Documents/periodicity_schedule.pdf.

26

25. Stead LF, Buitrago D, Preciado N, Sanchez G, Hartmann-Boyce J, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev. 2013 May 31;(5):CD000165. doi(5):CD000165. 26. Conde-Agudelo A, Rosas-Bermudez A, Kafury-Goeta AC. Birth spacing and risk of adverse perinatal outcomes. JAMA 2006;295:1809-23. 27. Venkataramani M, Cheng TL, Solomon BS, Pollack CE. How Often Are Parents Counseled About Family Planning During Pediatric Visits? Results of a Nationally Representative Sample. Acad Pediatr. 2017 Jul;17(5):476-478. 28. Rosener SE, Barr WB, Frayne DJ, Barash JH, Gross ME, Bennett IM. Interconception Care for Mothers During Well-Child Visits With Family Physicians: An IMPLICIT Network Study. The Annals of Family Medicine. 2016 July 01;14(4):350-5. 29. Stulberg DB, Dahlquist IH, Disterhoft J, Bello JK, Hunter MS. Increase in contraceptive counseling by parimary care clinicians after implementation of One Key Question at an urban community health center. Matern Child Health J. 2019;23(8):996.1002. 30. Allen D, Hunter MS, Wood S, Beeson T. One Key Question®: First Things First in Reproductive Health. Matern Child Health J. 2017 Mar;21(3):387-392. 31. Shannon GD, Alberg C, Nacul L, Pashayan. Preconception healthcare delivery at the population leve: construction of public health models of preconception care. Matern Child Health J 2014;18:1512-31. 32. Venkataramani M, Cheng TL, Solomon BS, Pollack CE. Addressing Parental Health in Pediatrics: Physician Perceptions of Relevance and Responsibility. Clin Pediatr (Phila). 2017 Sep;56(10):953-958. 33. Ford I, Norrie J. Pragmatic trials. N Engl J Med 2016; 375:454-463.

27