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Protocol for a randomised trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada)
  1. Cindy-Lee Dennis1,2,
  2. Flavia Marini2,
  3. Jennifer Abbass Dick3,
  4. Stephanie Atkinson4,
  5. Jon Barrett5,6,
  6. Rhonda Bell7,
  7. Anick Berard8,9,
  8. Howard Berger2,5,
  9. Hillary K Brown10,11,
  10. Evelyn Constantin12,13,
  11. Deborah Da Costa13,14,
  12. Andrea Feller15,
  13. Astrid Guttmann16,17,
  14. Magdalena Janus18,
  15. K S Joseph19,
  16. Peter Jüni2,20,
  17. Sarah Kimmins21,
  18. Nicole Letourneau22,
  19. Patricia Li12,
  20. Stephen Lye23,
  21. Jonathon L Maguire2,24,
  22. Stephen G Matthews23,25,
  23. David Millar26,
  24. Dragana Misita7,
  25. Kellie Murphy5,27,
  26. Anne Monique Nuyt9,12,
  27. Deborah L O'Connor17,28,
  28. Rulan Savita Parekh17,24,
  29. Andrew Paterson11,17,
  30. Martine Puts1,
  31. Joel Ray2,11,16,
  32. Paul Roumeliotis29,
  33. Stephen Scherer17,30,
  34. Daniel Sellen11,28,
  35. Sonia Semenic13,31,
  36. Prakesh S Shah24,27,
  37. Graeme N Smith32,
  38. Robyn Stremler1,17,
  39. Peter Szatmari17,33,34,
  40. Deanna Telnner35,
  41. Kevin Thorpe11,
  42. Mark S Tremblay36,37,
  43. Simone Vigod16,34,38,
  44. Mark Walker39,40,
  45. Catherine Birken17,24
  1. 1Lawrence S. Bloomburg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada
  2. 2St Michael’s Hospital, Toronto, Ontario, Canada
  3. 3Faculty of Health Sciences, University of Ontario Institute of Technology, Oshawa, Ontario, Canada
  4. 4Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
  5. 5Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
  6. 6Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  7. 7Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
  8. 8Faculty of Pharmacy, University of Montreal, Montreal, Québec, Canada
  9. 9Saint Justine Hospital, Montreal, Québec, Canada
  10. 10Department of Health & Society (Scarborough Campus), University of Toronto, Toronto, Ontario, Canada
  11. 11Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  12. 12Department of Pediatrics, McGill University, Montreal, Québec, Canada
  13. 13McGill University Health Centre, Montreal, Ontario, Canada
  14. 14School of Physical and Occupational Therapy, McGill University, Montreal, Québec, Canada
  15. 15Niagara Region Public Health, Thorold, Ontario, Canada
  16. 16Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  17. 17The Hospital for Sick Children, Toronto, Ontario, Canada
  18. 18Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
  19. 19Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada
  20. 20Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  21. 21Department of Animal Science, McGill University, Montreal, Québec, Canada
  22. 22Faculty of Nursing, University of Calgary, Calgary, Alberta, Canada
  23. 23Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
  24. 24Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
  25. 25Department of Physiology, University of Toronto, Toronto, Ontario, Canada
  26. 26Monarch Maternal and Newborn Health Centre, Ottawa, Ontario, Canada
  27. 27Mount Sinai Hospital, Toronto, Ontario, Canada
  28. 28Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
  29. 29Eastern Ontario Health Unit, Cornwall, Ontario, Canada
  30. 30Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
  31. 31Ingram School of Nursing, McGill University, Montreal, Québec, Canada
  32. 32Department of Obstetrics and Gynecology, Queen’s University, Kingston, Ontario, Canada
  33. 33Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  34. 34Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  35. 35Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
  36. 36Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  37. 37Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada
  38. 38Women's College Hospital, Toronto, Ontario, Canada
  39. 39Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
  40. 40The Ottawa Hospital, Ottawa, Ontario, Canada
  1. Correspondence to Professor Cindy-Lee Dennis; cindylee.dennis{at}utoronto.ca

Abstract

Introduction The ‘Developmental Origins of Health and Disease’ hypothesis suggests that a healthy trajectory of growth and development in pregnancy and early childhood is necessary for optimal health, development and lifetime well-being. The purpose of this paper is to present the protocol for a randomised controlled trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada). The primary objective of HeLTI Canada is to determine whether a 4-phase ‘preconception to early childhood’ lifecourse intervention can reduce the rate of child overweight and obesity. Secondary objectives include improved child: (1) growth trajectories; (2) cardiometabolic risk factors; (3) health behaviours, including nutrition, physical activity, sedentary behaviour and sleep; and (4) development and school readiness at age 5 years.

Method and analysis A randomised controlled multicentre trial will be conducted in two of Canada’s highly populous provinces—Alberta and Ontario—with 786 nulliparous (15%) and 4444 primiparous (85%) women, their partners and, when possible, the first ‘sibling child.’ The intervention is telephone-based collaborative care delivered by experienced public health nurses trained in healthy conversation skills that includes detailed risk assessments, individualised structured management plans, scheduled follow-up calls, and access to a web-based app with individualised, evidence-based resources. An ‘index child’ conceived after randomisation will be followed until age 5 years and assessed for the primary and secondary outcomes. Pregnancy, infancy (age 2 years) and parental outcomes across time will also be assessed.

Ethics and dissemination The study has received approval from Clinical Trials Ontario (CTO 1776). The findings will be published in peer-reviewed journals and disseminated to policymakers at local, national and international agencies. Findings will also be shared with study participants and their communities.

Trial registration number ISRCTN13308752; Pre-results.

  • community child health
  • public health
  • clinical trials
  • preventive medicine
  • social medicine
  • quality in health care
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Strengths and limitations of this study

  • The Healthy Life Trajectory Initiative (HeLTI) Canada study will be the first trial to determine whether a public health nurse facilitated telephone-based intervention with e-health resources, from preconception through early childhood, compared with a standard care control group, will reduce child obesity and adiposity while improving body mass index (BMI) trajectories, cardiometabolic risk factors, health behaviours and child development at age 5 years.

  • The HeLTI Canada study will examine outcomes of the whole family, including the mother, father, the index child and any sibling child who will be 3–12 months old at trial enrolment.

  • Harmonisation of core study measures and outcomes with the four HeLTI studies (Canada, China, India and South Africa) will enable pooled analyses of outcomes and direct comparisons.

  • Participation level of fathers is unknown and may require different approaches and incentives.

  • Detailed measures of body composition, such as air displacement plethysmography, are not feasibly measured in HeLTI Canada and more practical measures of anthropometry including BMI will be used.

Background

Non-communicable diseases (NCDs), including cardiovascular disease, type 2 diabetes mellitus and mental illness, are major global contributors to premature death and disability.1 2 In Canada, NCDs account for an estimated 89% of all mortality of which cardiovascular disease accounts for 33% of all deaths.3 Cardiometabolic disease—hypertension, coronary artery disease and diabetes—has risen in prevalence globally in parallel with economic development, urbanisation, an obesogenic lifestyle and obesity.4–6 In Canada, 60% of men and 50% of women are overweight or obese,7 forecasting serious economic, societal and individual health consequences.8 Today, 27% of children in Canada are overweight or obese with rates steadily increasing.9 Accelerated growth in infancy and early childhood is a strong risk factor for obesity in older children. A higher body mass index (BMI) in the preschool-aged child is associated with subclinical atherosclerosis in adulthood.10 Childhood overweight and obesity can also impact child development,11–13 with negative effects found related to cognitive function,14 social achievement and emotional well-being.15–18 This is important given that one in five Canadian children has a mental health problem.19

Intrauterine and early infancy exposures appear to influence a person’s risk of adult-onset chronic diseases20—the core idea of the ‘Developmental Origins of Health and Disease’ hypothesis.21 Suboptimal maternal nutrition in pregnancy can lead to fetal growth restriction, and a sequence of overcompensatory responses that predispose to cardiometabolic disease in adulthood.22 Low birth weight and in utero exposure to maternal diabetes, hypertension and obesity are each associated with elevated blood pressure, plasma glucose, insulin and lipid concentrations in children at age 5 years.23–25 These childhood risk markers at age 5 years and beyond further predict cardiometabolic disease in adulthood.26–31 A similar sequence has been described with a well-studied list of exposures in pregnancy or early infancy: (1) maternal obesity;27 28 32 (2) gestational diabetes (associated with fetal hyperinsulinaemia and excess fetal adiposity);23–25 33 (3) maternal smoking;34 35 (4) formula feeding in infancy;36 and (5) fetal/infant exposure to stress or parental depression.37–39

The preconception period represents an important life stage when exposures can damage germline DNA and epigenetically alter gene expression, subsequently impacting offspring outcomes.40–43 A narrative review of preconception interventions to prevent obesity and NCD in children found that no study reported directly on obesity and NCD in children, but rather research to date has focused mainly on pregnancy outcomes and birth weight.44 Existing approaches tend to focus solely on the mother. Increasingly, scientific evidence shows that the preconception health of the future father is also important,45 representing an unrealised, underdeveloped and understudied opportunity.

A meta-analysis of 38 studies found a consistent relationship between maternal pre-pregnancy weight and child obesity.46 Maternal pre-pregnancy obesity is also linked to the hypertensive disorders of pregnancy, gestational diabetes, high infant birth weight and shorter breastfeeding duration.45 47–54 A meta-analysis of 23 trials55 found that preconception interventions can positively modify maternal health behaviours, including calorie restriction with increased physical activity, that when reinforced by a support system and monitoring can be sustained over longer time periods.56 Importantly, growing evidence suggests that health behaviour interventions, even those producing a modest change, can successfully and efficiently reduce metabolic disease risk in pregnancy.57–59 A meta-analysis of 23 studies found maternal exposure to smoking in pregnancy was associated with increased risk of child obesity.46 Fetal exposure to maternal smoking impacts prematurity, low birth weight, congenital malformations and sudden infant death syndrome,60–65 suggesting psychosocial smoking cessation programmes66 are warranted before conception. Paternal smoking is also associated with childhood cancer, cardiovascular disease and obesity, not only in the child but grandchildren as well possibly through epigenetic mechanisms.67 68 Mental illness is common in women and men of reproductive age, of which a substantial proportion go untreated, especially during pregnancy and postpartum. Parental mental illness negatively affects the entire family and increases a child’s risk for poor cognitive, behavioural and emotional developmental trajectories. The recognised association between mental illness and obesity supports evaluation of whether treating the former preconceptionally can reduce the latter.69 Accordingly, we will deliver evidence-based preconception interventions targeting both a woman and her partner, that align with current evidence suggesting that parental BMI, diet, lifestyle and mental health might alter pregnancy and child health outcomes.

The Healthy Life Trajectory Initiative (HeLTI) was developed in partnership with research teams from Canada, China, India and South Africa and in collaboration with the WHO to address the increasing burden of NCDs around the world. Four separate randomised controlled trials implemented in Soweto (South Africa), Mysore (India), Shanghai (China), and the provinces of Ontario and Alberta (Canada) have been harmonised. All trials are focused on developing evidence-based interventions that span from preconception across pregnancy and into the postnatal period with the primary goal of reducing child obesity and improving maternal, paternal, and child health and well-being. The protocol described here is for HeLTI Canada, one of the four trials in the HeLTI initiative.

Consistent with the international HeLTI studies, our main objectives are to determine whether the complete four-phase (preconception, pregnancy, infancy and early childhood) intervention, compared with standard care, can among index children at age 5 years: (1) reduce overweight and obese status; (2) reduce zBMI and improve zBMI trajectories; (3) reduce adiposity; (4) improve cardiometabolic risk factors; (5) enhance development and school readiness; and (6) improve health behaviours, including nutrition, physical activity, screen time and sleep. We will also examine the impact of the intervention on parental outcomes across time. We will determine the ‘cumulative-impact’ of the four-phase intervention, including the effect of the preconception phase on parental outcomes at the time of conception; the effect of the preconception+pregnancy phases on pregnancy outcomes; and the effect of the preconception+pregnancy+infancy phases on child outcomes at age 2 years. Our unique study design also provides an opportunity to understand the effect of the infancy+early childhood phases of the intervention on ‘sibling child’ outcomes at age 5 years. The Glass and McAtee70 childhood obesity model provides a general overarching conceptual framework modified based on meta-analytic data on child obesity risk factors.46 Our study will target modifiable risk factors for childhood obesity during the four phases of the intervention.

Methods/design

Study design

A randomised controlled multicentre trial will be conducted in Canada with 5230 women who are planning to be pregnant within the next 3 years. We will recruit up to 786 nulliparous (15%) and at least 4444 primiparous (85%) women, their partners, and, when possible, the first ‘sibling child.’ These women will be randomly allocated in a 1:1 ratio to the four-phase preconception-early childhood intervention or to usual care, using individual, web-based and central randomisation. An ‘index child’ conceived after randomisation (n=3660; 70%) will be followed until age 5 years and assessed for the primary and secondary outcomes. Pregnancy, infancy (at age 2 years) and parental outcomes will also be assessed. In addition, among the 4444 primiparous women planning their second pregnancy, their preceding first child (called the ‘sibling child’), eligible range 3–12 months when the mother is randomised, will also be followed until age 5 years. This concurrent randomised trial will compare those intervention phases specific to infancy and early childhood versus usual care in these ‘sibling’ children. This added component will allow us to estimate the additional effectiveness of the preconception+pregnancy phases of the intervention (which are only received by the index child), beyond that of the infancy+early childhood phases of the intervention (which are also received by the sibling child), while fully preserving randomisation. Couples who do not conceive will complete an exit assessment 3 years postrandomisation.

Setting

The trial will be conducted in two of Canada’s highly populous provinces, Alberta (4.4 million) and Ontario (14.6 million), from three main recruitment settings: (1) public health regions; (2) obstetric and postpartum clinics; and (3) primary care practices and community healthcare centres that provide postpartum and well-child care in Alberta and Ontario. The selected public health regions are strategically located in Edmonton and across Ontario, including rural regions to promote participant diversity. In total, recruitment will be from eight public health regions of which seven are in Southern Ontario (Toronto, Durham, York, Peel, Halton, Hamilton and Niagara) and one is in Alberta (Edmonton). In Edmonton and the surrounding area, the Healthy Living, Population, Public and Indigenous Health team in Alberta Health Services will participate. The obstetric clinics that will participate include those at Mount Sinai Hospital, Sunnybrook Hospital and North York General Hospital. The selected primary care practices are all affiliated with TARGet Kids! in the Greater Toronto Area, where healthy children and their parents are enrolled in a prospective cohort with embedded studies at their primary care practices and followed at their well-child visits. We will also recruit participants via postpartum health clinics (Monarch Centre) in Ottawa and social media including Facebook and Google ads.

Inclusion/exclusion criteria

The target population consists of non-pregnant women who meet the following entry criteria: (1) nulliparous (no children) or primiparous (one child) between 3 and 12 months postpartum; (2) planning a pregnancy in the next 3 years; and (3) understands spoken and written English. Excluded are women with (1) type 1 diabetes; (2) parity ≥2; and (3) residence significantly outside of the eight identified health regions or Ottawa area. If a woman has a twin birth, the first child born will be the index child. Single women and those with same-sex partners will be included.

Study design overview

Our intervention will take a ‘cumulative-impact’ approach designed to improve health behaviours (eg, nutrition, physical activity, screen time and sleep) and reduce modifiable risk factors that influence child obesity. The intervention will start prior to conception and continue through to early childhood. It will be evidence-based, professionally facilitated, proactive, individualised, multifaceted, and sex-specific and gender-specific. It will build on existing research and clinical resources while recognising the growing trend of e-health.71 Local stakeholders, such as public health nurses/family physicians, will participate in providing services and referrals to ensure the intervention is tailored to local circumstances. Our intervention will target not only women, but also their partners and other key individuals in the child’s environment who can influence child health, such as grandparents, if appropriate. Among primiparous women, we will also provide information and support to promote healthy growth and development with the sibling child with the goal of taking a family-approach to care. Our intervention, with its foundation on public health and primary care platforms and e-health technologies, is structured to facilitate scalability across Canada, if effective.

Preconception-early childhood intervention

The intervention will be provided in four phases: (1) preconception, (2) pregnancy, (3) infancy (0–2 years), and (4) early childhood (3–5 years). Each phase has time-sensitive goals based on child obesity risk factor meta-analyses.46 To achieve these goals, two core strategies will be used throughout the four phases: (1) public health nurse collaborative care and (2) an individualised webpage as part of the responsive HeLTI Canada app that will include expert-selected e-health resources. Systematic reviews for each of these intervention strategies have demonstrated their growing effectiveness in improving health behaviours and clinical outcomes.72–76 We will combine these two different strategies, which will allow us to: (1) reach participants, including those in rural/remote locations or those with transportation limitations; (2) provide support that is convenient and accessible 24 hours/day; (3) offer multiple options for peer/professional support; and (4) deliver care at a low cost.77

Public health nurse collaborative care

Women allocated to the intervention group will be assigned an experienced public health nurse (HeLTI nurse) hired and trained by the team to provide telephone-based collaborative care starting within a week of randomisation. The HeLTI nurses are trained in Healthy Conversation Skills, an evidence-based client-centred programme developed by UK researchers at Southampton University, designed to support health behaviour change.78 The activities provided will include the standard criteria for collaborative care: (1) individual assessment; (2) structured management plan; and (3) scheduled follow-up.

Part I: Telephone assessment

At the beginning of each of the four intervention phases, the assigned HeLTI nurse will telephone the woman, complete an assessment based on phase goals and identify potential preconception risks.

Part II: Structured management plan

The HeLTI nurses’ role will be to: (1) educate the woman and her partner (if applicable) about identified preconception risks and management options; (2) assess management barriers and preferences; and (3) coordinate a management plan with appropriate public health, primary care and community services.

Part III: Scheduled follow-up

The HeLTI nurse will telephone participants every 2 weeks to follow-up on management plans and track targeted behaviours. Based on behaviour modification and reduced risk, the participant will move from the ‘active phase’ of the intervention to the ‘continuation phase’. During this phase, participants will receive telephone follow-up every 2 months until completion of the phase. At the beginning of each phase, participants return to the ‘active phase’ of the intervention with telephone calls every 2 weeks. All participants have the option to proactively call their HeLTI nurse as needed. All intervention activities will be documented including email and text exchanges and referrals to health and social services.

Responsive HeLTI app

A responsive web-based HeLTI Canada app will be developed with easy access functionality. Each woman and her partner will be provided with their own secure login to a site that includes personalised web-based educational materials and apps based on the needs identified by their HeLTI nurse. Our expert-recommended e-health resources and apps will be easily accessible on a mobile device, tablet or computer and will enable us to provide innovative and engaging support to participants with diverse health issues. All e-health resources and apps will be reviewed and updated annually.

Usual care–control group

Women allocated to the control group will have access to standard care provided to all women from preconception to early childhood (child age 5), but they will not receive the preconception-early childhood intervention. However, as a retention strategy, they will also have access to their own individualised webpage with secure login to receive injury prevention and child safety e-health resources based on recommendations from experts from York University and the University of British Columbia.79 Focus groups with parents suggested this would be useful information and the content will not be directly related to the trial primary and secondary outcomes.

Outcomes and frequency of follow-up

All participants will be asked to complete online questionnaires via REDCap,80 a secure, encrypted web-based electronic data capturing system, at baseline and at scheduled intervals during preconception (12, 24 and 36 months postrandomisation or until conception), pregnancy (24–28 weeks’ gestation), infancy (3, 6, 12 and 24 months following delivery) and early childhood (36, 48 and 60 months following delivery) phases of the trial (figure 1). Specific outcome measures are presented in table 1. Participants who do not complete any follow-up questionnaires within 2 weeks will be telephoned by a trained research assistant blinded to group allocation to provide a reminder and the REDCap questionnaire link will be resent via email. All women and their partners who complete a questionnaire will be provided with a $C15 gift card. Participants will also be asked to provide clinical data (height, weight, arm and waist circumference, and blood pressure)46–48 81 82 via a scheduled visit to designated community-based clinics or by home visits, if requested by the participant. Biospecimen data (eg, blood) will also be collected from a voluntary subsample of participants (n=1000) who live in the Greater Toronto Area. We will link health card numbers of consenting mothers, partners and children to provincial health administrative data that will allow for long-term follow-up for inpatient and outpatient physician diagnoses and procedures, including emergency department and hospitalisation data, and Early Development Instrument data for children. In Ontario, this includes linkage to Better Outcomes Registry and Network Ontario,83 a clinical registry with detailed obstetrical and neonatal data for all Ontario in-hospital and out-of-hospital births. Relevant to the current study, this clinical registry will be used to collect data on birth outcomes, including infant birth weight and gestational age. In Alberta, we will use the Alberta Perinatal Health Program, which captures information about all births (and pregnancies).

Table 1

HeLTI Canada outcome measures

Figure 1

HeLTI Canada study flow diagram. *Biospecimen data (eg, blood and urine) will also be collected at these time-points from a voluntary subsample of participants who live in the Greater Toronto Area. HeLTI, healthy life trajectory initiative.

Biospecimen collection and management

It is anticipated that future substudies may require additional biospecimens and supplementary external funding. At baseline, biospecimens will be collected, processed and aliquoted by trained technicians at a province-wide professional lab (LifeLabs) using established standard operating procedures aligned with those outlined at the Global Alliance to Prevent Prematurity and Stillbirth repository. Biospecimens will be stored at Lunenfeld-Tanenbaum Research Institute’s established biorepository. The laboratory fully complies with the Canadian laboratory accreditation programme.

Sample size

Current estimates in Canada suggest that ~25% of children at age 5 years are overweight or obese, defined as greater than the 85th percentile for age and sex standardised BMI.84 A reduction of overweight and obesity rates of 20% is aligned with the goals of the National Framework for Action to Promote Healthy Weights85 and provincial recommendations, including the Ontario Ministry of Health. At age 5 years, 1464 children per group (2928 in total) are required to detect a clinically meaningful 20% relative reduction, corresponding to an absolute reduction of 5% with 90% power at a two-sided alpha of 0.05 for the primary randomised comparison of the preconception-lifecourse intervention versus control. Allowing for 20% attrition from conception to age 5 years, 3660 viable conceptions are required. We expect that an average of 70% of women will conceive within 3 years of recruitment and subsequently give birth. This estimate is conservative: The 2013 guidelines on assessing and treating fertility problems of the UK National Institute of Health and Care Excellence estimate the cumulative probability to conceive a viable pregnancy after 2 years (24 cycles) among women without contraception to be 98% for age 19 to 26% to 90% for age 35–39 years86 based on data from a contemporaneous cohort of 782 women from Western European centres.81 Estimates in a frequently cited article by Heffner87 are somewhat lower, but these are 1-year estimates based on historical cohorts of women88 and are still compatible with our assumptions, with an estimated probability of conception of 86% in women aged 20 to 24% to 70% in women aged 35–39 years after 3 years (36 cycles). Therefore, 5230 women will need to be recruited.81 89 The sample size for this trial will also yield more than 95% power to detect a minimal clinically important difference in age-standardised and sex-standardised BMI z-score of 0.25 between groups.90 91 Our sample size will yield more than 95% power to detect the minimally clinically important difference of 0.25 SD units between groups. The study design will also allow for evaluation of the infancy to early childhood phase of the intervention for the sibling child: Assuming that 85% of women will be primiparous and be randomised when their first, sibling child is aged 6 months (eligible range 3–12 months), up to 4444 children will be included in a concurrent, powered second randomised comparison of the lifecourse intervention received during infancy to early childhood phase versus control. This sample size provides more than 95% power for the same outcome and treatment effect as above after accounting for 20% attrition.

Patient and public involvement

Formative work with over 1300 Canadian families was completed to understand preconception needs, prevalence of preconception risk factors, trial recruitment strategies, intervention preferences and key strategies for disseminating trial results.

Planned analyses

Primary and concurrent secondary randomised comparisons will be analysed independently and hypothesis testing will use a two-sided 0.05 significance level for both comparisons. Since outcomes are identical in the two concurrent comparisons, the same methods will be used. Primary outcome and binary secondary outcomes will be compared by means of a χ2 test and treatment effects will be expressed as absolute risk differences with 95% CI. Continuous secondary outcomes will be compared by an independent t-test and treatment effect will be expressed as the mean difference with 95% CI. Additional analyses of pregnancy and parental outcomes will be done using the same approaches. If baseline values are available for continuous parental outcomes, however, we will use analysis of covariance adjusted for baseline values for these outcomes. As secondary outcomes are considered exploratory in nature, we will not adjust for multiple comparisons.

All outcome data will be analysed according to the intention-to-treat principle, analysing all individuals in the group they were originally allocated to. The primary approach for these analyses will be a complete case analysis, including all individuals with available data. Two types of sensitivity analyses will be performed to account for missing outcome data, using multiple imputation92 and inverse-probability weighting.93 Results from these sensitivity analyses will be reported along with the primary analyses. For multiple imputation, we will use baseline characteristics of mothers and outcomes of children in the imputation model to create 20 imputed data sets. Standard errors will be calculated using Rubin’s rules,94 taking the variability in results between the imputed data sets into account. For inverse-probability weighting, we will calculate the probability of having complete outcome data for each individual using logistic regression; observations will then be weighted by the inverse of these probabilities and outcome models will be built to approximate results of a trial with no missing information.93 To determine the relative effectiveness of the preconception intervention as compared with the infancy intervention, we will do indirect comparisons that fully preserve randomisation.95 As up to two children per mother can be included in these analyses, we will use mixed maximum-likelihood logistic and linear regression models, which allow for the correlation of children within families. Prespecified subgroup analyses will be performed by sex and by number of children in the family (one versus two) and accompanied by tests for interaction between treatment effect and subgroup.

Data management and oversight

We will work with the international HeLTI research teams to establish a detailed collaborative plan and governance/management structure to ensure that the HeLTI initiative objectives are met. A data monitoring committee (DMC) has been established. The DMC is independent of sponsors and competing interests. The principal investigators (PIs; Dennis and Birken) of the Canadian team will sit on the international HeLTI Research Committee, while Canadian workgroup leads will contribute to the international HeLTI working groups. At the HeLTI Canada office, an experienced research manager will oversee the whole HeLTI Canada study while a trial coordinator will be responsible for the day-to-day trial management. Research assistants will be hired to perform recruitment activities (detailed explanation about the study, consent form and eligibility screening) while others, blinded to group allocation, will complete follow-up data collection activities for non-responders and gift card management; they will also receive extensive training and will be able to collect any REDCap outcome data via telephone if necessary. HeLTI nurses will be hired and extensively trained to deliver and document the intervention. Women and their partners in both groups will have access to usual standard care across all intervention phases. During depression screens, any participant who has a positive response on the Edinburgh Postnatal Depression Scale (EPDS) self-harm ideation item will be further assessed by trained research staff.96 In addition, for ethical reasons, local public health nurses will be notified of all participants scoring very high (>20) on any EPDS or Patient Health Questionnaire-9 assessment. We will follow a protocol for infant/child harm if we suspect any potential child abuse/neglect. All these safety strategies have been effectively used previously by Dennis (lead PI).97–101 Negative intervention effects will be assessed through participant evaluations. All data will be managed through REDCap, which is fully configurable and incorporates validation rules to ensure high quality data. It allows for remote web-based data entry directly from the participating sites. REDCap will be managed by the Applied Health Research Centre at the Li Ka Shing Knowledge Institute, St. Michael’s Hospital (Toronto).

Nearly one in three Canadian children are overweight or obese, and interventions to prevent obesity have been largely unsuccessful. This randomised controlled trial, conducted with pregnancy planning women and their partners, will evaluate whether an intervention starting in the preconception period and continued to early childhood can reduce child overweight and obesity, and improve developmental trajectories and mental health, compared with usual standard care. The harmonisation of the intervention and outcomes across the four HeLTI studies (Canada, India, China and South Africa) will enable pooled analysis and direct comparisons. If effective, this telephone-based intervention with e-health resources may be scalable to other sites and settings.

Acknowledgments

We thank the families who participated in the formative work to assist us in the development of the Healthy Life Trajectory Initiative Canada trial.

References

Footnotes

  • Contributors CLD and CB are co-principal investigators for Healthy Life Trajectory Initiative Canada. CLD, CB and FM wrote the initial protocol draft. JAD, SA, JB, RB, AB, HBe, HBr, EC, DDC, AF, AG, MJ, KJ, PJ, SK, NL, PL, SL, JLM, SGM, DaM, DrM, KM, AMN, DLO, RSP, AP, MTEP, JR, PR, SS, DS, SS, PSS, GNS, RS, PS, DT, KT, MST, SV and MW read and contributed to the final version. All authors provided edits and critiqued the manuscript for intellectual content.

  • Funding This work was supported by Canadian Institutes of Health Research (CIHR), grant number HLC-154502.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

  • Ethics approval Approval provided by Clinical Trials Ontario and the University of Alberta.

  • Provenance and peer review Not commissioned; peer-reviewed for ethical and funding approval prior to submission.

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