Effect of a prepartum and postpartum, complex interdisciplinary lifestyle and psychosocial intervention on metabolic and mental health outcomes in women with gestational diabetes mellitus (the MySweetheart trial): randomised, single centred, blinded, controlled trial

Objective To test the effect of a complex, interdisciplinary, lifestyle and psychosocial intervention on metabolic and mental health outcomes in women with gestational diabetes mellitus during pregnancy and in the post partum. Design Single centred, single blinded, randomised, controlled trial (the MySweetheart trial). Setting Lausanne University Hospital, Switzerland, from 2 September 2016 to 25 October 2021. Participants 211 women aged at least 18 years with a diagnosis of gestational diabetes mellitus at 24-32 gestational weeks were randomly assigned (1:1) to the intervention (n=105) or to usual care (n=106). Interventions In addition to a comparator based on active guidelines for prepartum and postpartum usual care, the intervention consisted of four individual lifestyle visits during pregnancy and four interdisciplinary visits in the postpartum group, a peer support group workshop in pregnancy and post partum, and a bimonthly lifestyle coach support through telemedicine. The intervention focused on tailored behavioural and psychosocial strategies to improve diet, physical activity, mental health, social support, and adherence to gestational weight gain during pregnancy and weight retention recommendations. Main outcome measures Primary outcomes were between-group differences in the decrease in maternal weight and depression symptom scores between baseline and one year post partum. Secondary outcomes included changes in total and central body fat, anxiety, wellbeing, glycaemic parameters (homeostatic model assessment for insulin resistance (known as HOMA-IR) and Matsuda indices), aerobic fitness (maximal oxygen uptake), gestational weight gain, and weight retention. Assessors were blinded to primary and secondary outcomes. Results 84 (80%) of 105 women in the intervention and 95 (90%) of 106 in the usual care completed the study. There was not enough evidence of a difference in the decrease in weight (mean difference –0.38 kg (95% confidence interval –2.08 to 1.30)) or depression scores (–0.67 (–1.84 to 0.49)). The intervention led to an increase in fat-free mass (0.02 kg (0.01 to 0.03)). The intervention also decreased gestational weight gain since the first gestational diabetes mellitus visit (–1.20 kg (–2.14 to –0.26)) and weekly weight gain throughout the entire pregnancy (–0.14 kg (–0.25 to –0.03)), and led to a higher proportion of women without weight retention at one year post partum (34.1% (28/82) v 20.8% (20/96), P=0.034). Conclusions Compared with active usual care based on guidelines, there was not enough evidence to conclude that the intervention led to decrease in weight or depression symptoms. However, the intervention decreased gestational weight gain and increased the proportion of women without weight retention. Trial registration Clinicaltrials.gov NCT02890693.


Trial registration:
The study will be registered on clinicaltrials.govand kofam.ch

Study category and Rationale
MyS weetHeart study is composed of two sub-studies: (A) MySweetHeart Trial: a randomized clinical trial with an intervention entailing minimal risks and burdens (risk category A); (B) MySweetHeart Cohort: an observational cohort study ent ailing minimal risks and burdens (risk category A).

Clinical Phase:
Not applicable

Background and Rationale:
Gestational diabetes mellitus (GDM) is a state of glucose intolerance with onset during pregnancy.It is common with prevalence estimates larger than 10% in several populations.GDM carries pre-and perinat al risk for the mother (e. g., pre-eclampsia or preterm delivery) and the infant (e.g.macrosomia or neonatal hypoglycemia) as well as long term risks for the mother (e.g., type 2 diabetes, metabolic syndrome, and cardiovascular disease) and her child (e.g., obesity and type 2 diabetes).Compared to women without GDM, women with GDM are twice as likely to develop perinatal or postpartum depression and approximately one -third of women with recent GDM develop postpartum depression.
Lifestyle interventions for the treatment of GDM are often limited to physical activity or nut rition, for the mother or the child separately, either only during or only after pregnancy.Their effects are inconsistent.The multifactorial origins of GDM and the tight link between mental and metabolic as well as maternal and child health calls for a multidimensional interdisciplinary approach.
Furthermore, maternal GDM may be involved in the fetal programming of long-term cardiovascular health.However, evidence is sparse and the effect of GDM on cardiovascular health is not known.
To address these issues, we will conduct MyS weet Heart Study, which is composed of two sub-studies (A) MySweetHeart Trial (PI: Prof. J. Puder and Dr A. Horsch) and (B) MySweetHeart Cohort (P I: Prof. N. Sekarski and Dr A. Chiolero; funded by the SNF).Both sub-studies will be conducted in complete coordination.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.

A) Overall objective of MySweetHeart Trial
To test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve the cardio-met abolic and mental health of women with GDM and their offspring.

A1) Primary objective of MySweetHeart Trial
To test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention in women with GDM to improve 1) their metabolic (decrease in maternal weight between 24-32 weeks gestational age and the end of t he study at 1 yr postpartum) and 2) their mental (decrease in maternal symptoms of depression during the same time period) health.

A2) Secondary objectives of MySweetHeart Trial
To test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve other cardio-metabolic and mental health markers in women with GDM and their offspring.

B) Overall objective of MySweetHeart Cohort
To assess the effect of GDM on offspring cardiovascular health early in life

B1) Primary objective of MySweetHeart Cohort
To assess the effect of GDM on the surrogat e markers of cardiovascular disease (CV D) at birth (left ventricular mass index and subclinical atherosclerosis)

B2) Secondary objectives of MySweetHeart cohort
To assess the effect of GDM on the c ardiovascular structure and function during the fetal period and neonatal adverse cardiovascular risk factors

Outcome(s): A1) Primary outcomes of MySweetHeart Trial
Differences bet ween the intervention and t he cont rol group in (1) the decrease in maternal weight between 24-32 weeks gestational age and yr postpart um and (2) the decrease in maternal symptoms of the Edinburgh postnatal depression score (EPDS) during the same time period.

A2) Secondary Outcomes of MySweetHeart Trial
Differences between the intervention and the control group in other maternal secondary outcomes, such as (1) lifestyle behaviours, aerobic fitness and strength, body composition and cardio-metabolic laboratory biomarkers and (2) other mental health indicat ors during the peri-and postpart um period and offspring s econdary outcomes, such as (1) cardiometabolic laboratory biomarkers at birth, body composition at birth and at yr of age; and (2) mental health indicators at 1 yr of age.

B1) Primary outcomes of MySweetHeart Cohort
Differences in surrogat e markers of CVD at birth [left ventricular mass index (LVMI) and subclinical atherosclerosis (carotid intima -media thickness; cIMT)] between offspring of women with GDM and offspring of women without GDM.

B2) Secondary outcomes of MySweetHeart Cohort
Differences in cardiovascular structure and function during the fetal period (fetal cardiovascular alterations, LVMI, liver volume), and neonat al adverse cardiovascular risk factors between offspring of women with GDM and offspring of women without GDM.

Study design: A) Study design of MySweetHeart Trial:
Randomized control trial (RCT) testing the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention compared with treatment-as-usual in women with GDM and their offspring.

B) Study design of MySweetHeart Cohort:
Cohort study comparing cardiovascular health between offs pring of wom en with GDM and offspring of women without GDM.

Inclusion / Exclusion criteria:
Inclusion criteria: Women aged 18 yrs or older, with or without GDM at 24-32 weeks of gestation, and understanding French or English.Exclusion criteria: Women on strict bed-rest, with pre-existing diabetes or known severe mental disorder BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.3 2024; BMJMED , et al.

Measurements and procedures:
Whenever it is possible, until birth, similar measurements and procedures will be followed for MyS weetHeart Trial and MyS weetHeart Cohort (see Table 1 and Table 2

for details).
A) MySweetHeart Trial : Patients and their offspring will be followed-up from 24-32 weeks gestational age 1 year postpartum.Once included, patients will be randomly allocated to the usual care (control) group or to the intervention group.The intervention, offered on top of the usual care, consists of individual sessions (face-to-face or telephone contact) with different members of the int erdisciplinary team (dietician, physiotherapist, clinical psychologist or coach) and t wo group s essions.The intervention will consist of dietary and physical activity advice, screening for and treatment of mental health problems, and increase of social support.It will take place during pregnancy and during the first year postpartum.The primary outcomes will be measured at 24-32 wks of gestation and at 1 year postpart um.Secondary and other outcomes will be measured at 30-34 wks of gestation, at birth, at 6-8 wks and 1 year postpartum.Partners will be assessed at study begin and at 1 year postpartum.

B) MySweetHeart Cohort:
Patients and their offspring will be followed up until a few days after birth.Primary outcomes will be measured a few days after birth.Secondary outcomes will be measured at 30-34 wks of gestation and at birth.

Study Product / Intervention:
Not applicable

Control Intervention (if applicable):
A

A) MySweetHeart Trial:
For the primary analyses, differences in the changes in maternal weight and the EPDS depression symptoms score between inclusion after GDM diagnosis and 1 year postpartum at the end of the study between the 2 groups will be analyzed using linear regression analysis .Analyses will be adjusted for the respective baseline values if there are differences between arms.Variables will be transformed if residuals are not normally distributed.We will include potential confounding variables, if necessary.The p otential confounding variables are maternal age, sex of the children, pre-, peri-and early postnatal conditions/complications, and socioeconomic status where applicable.

B) MySweetHeart Cohort:
The association between expos ure (GDM/no GDM) and the (continuous) primary outcomes will be estimated with linear regression analyses, with adjustment for potential confounding factors.We will also conduct similar analyses to assess the association between exposure (GDM/ no GDM) and secondary outcomes.Furthermore, the direct and indirect (through mediators) effect of GDM on the primary outcomes will be estimated by causal mediation analyses (notably with an adjustment on birt h weight to estimate the indirect effect -not mediated by gestational weight-of GDM on the outcomes).

GCP Statement:
This study will be conducted in complianc e with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO E N 14155 (as far as applicable) as well as all national legal and regulatory requirements.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)

Background
Gestational diabetes mellitus (GDM) is a state of gluc ose intolerance with onset during pregnancy that does not fulfil the criteria for diabetes.It is common with prevalence estimates larger than 10% in several populations.GDM carries pre-and perinatal risk for the mother (e.g., preeclampsia or preterm delivery) and the infant (e.g.macrosomia or neonatal hypoglycaemia) as well as longer-term risks for both the mother (e.g., type 2 diabetes, metabolic syndrome, and cardiovascular diseas e) and her child (e.g., obesity and type 2 diabetes).Compared to women without GDM, women with GDM are twice as likely to develop perinat al or postpart um depression and approximately one-third of women with recent GDM develop postpartum depression.Lifestyle interventions for the treatment of GDM are often limited to physical activity or nutrition.They often treat the mother or the child separately, and happen either only during or only aft er pregnancy, and results are inconsistent.The multifactorial origins of GDM and the tight link between mental and metabolic as well as maternal and child health c alls for an interdisciplinary approach.Furthermore, maternal GDM may be involved in the fetal programming of long-term cardiovascular health.However, evidence is sparse and the effect of GDM on the child's cardiovascular health is not known.
To address these issues, we will conduct MySweetHeart study composed of two sub-studies (A) MySweetHeart Trial (PI: Prof. J. Puder and Dr A. Horsch) and (B) MySweetHeart Cohort (P I: Prof. N. Sekarski and Dr A. Chiolero).Both sub-studies will be conducted in complete coordination.

A) Objectives of MySweetHeart Trial:
To test the effects of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve/in improving the cardio-metabolic and mental health of women with GDM and their offspring.The primary outcomes are differences bet ween the intervention and the cont rol group in (1) the decrease in maternal weight between 24-32 weeks gestational age and 1 yr postpartum and (2) the decrease in maternal symptoms of depression during t he same time period.Maternal secondary outcomes are (1) lifestyle behaviours, aerobic fitness and strength, body composition and cardio-metabolic laboratory biomarkers and (2) other mental health indicators during t he peri -and postpartum period.Offspring sec ondary outcomes are (1) cardio -metabolic laboratory biomarkers at birth, body composition at birth and at 1 yr of age; and (2) mental health indicators at 1 yr of age.Links between these outcomes will also be investigated.

B) Objectives of MySweetHeart Cohort:
To assess the effects of GDM on offspring cardiovascular health early in life.The primary outcomes are the differenc es in surrogate markers of CV D at birth [left ventricular mass index (LVMI) and subclinical atherosclerosis (carotid intima-media thickness; cIMT)] between offspring of women wit h or without GDM.The secondary outcomes are the differences in cardiovascular structure and function during the foetal period (foetal cardiovascular alterations, LVMI, liver volume), and neonatal adverse cardiovascular risk factors bet ween offspring of women with or without GDM.

Methodology A) MySweetHeart Trial:
monocentric superiority open randomized controlled trial (RCT) of 200 women with GDM and their offspring randomly assigned (1:1) to either the intervention (multidimensional interdisciplinary lifestyle and psychosocial intervention) or the control group (treatment -as-usual).Patients will be recruited at 24 -32wks of gestation after GDM diagnosis and will be followed-up with their offspring during the first year postpart um.The intervention, offered on top of usual care, consists of individual sessions (face-to-face or telephone contact) with different members of the interdisciplinary team (dietician, physiotherapist, clinical psychologist or coach) and two group sessions.The intervention will consist of: specific dietary and physical activity advice, screening for and treatment of mental health problems, and social support.It will take place during pregnancy and during the first year postpartum.Primary outcomes will be measured at inclusion and 1 year postpartum.Secondary outcomes will be measured at inclusion, 30-34 wks of gestation, and at 6-8 wks and 1 year postpartum.Assessors measuring the primary outcomes and the statistician will be blind t o group allocation.For the assessment of outcomes, validated questionnaires and standar dised devices, such as calibrated scales, accelerometer, bioimpedance, bone densitometry (Dual energy X-ray absorptiometry DXA), and standardised motor tests will be used.Biomarkers and questionnaires will be analysed by staff blind to group allocation.

B) MySweetHeart
Cohort: cohort study of 100 women with GDM that correspond to the above mentionned control group and their offs pring and of 100 women without GDM and their offspring.Patients will be recruited at 24-32 wks of gestation and will be followed-up with their offs pring until birth.Primary outcomes will be meas ured shortly (2-7 days) after birth.Secondary outcomes will be measured during t he foetal period (30 -34 wks of gestation), at birth, and shortly (2-7 days) aft er birth.A long-term follow-up of these children is planned but is not part of the current study protocol.

Anticipated results
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A) MySweetHeart Trial:
We hypothesize that, compared with patients in the c ontrol group, patients in the intervention group will have a greater decrease in maternal weight and in mat ernal symptoms of depression between 24-32 weeks gestational age and 1 yr postpartum.In addition, we anticipate that patients in the intervention group and their offspring will have better cardio-metabolic and mental health outcomes compared to patients and their offspring in the control group.

B) MySweetHeart Cohort:
We hypothesize that offspring of women with GDM have a larger LVMI and a larger cIMT at birth (primary outcomes) compared with offspring of women without GDM.Moreover, we hypothesize that offspring of women with GDM will have more foetal cardiovascular alterations and adverse neonatal cardiometabolic risk factors (secondary outcomes) compared with offspring of women without GDM.

Data Safety Monitoring Committee
There is no safety monitoring committee because the intervention is not associated with any substantial risk for the participants (see below point 5.4.Safety outcomes).

Any other relevant Committee, Person, Organisa tion, Institution
Not applicable.

Study registration
MySweetHeart Trial will be registered in clinicaltrials.govand kofam.chafter the positive decision of the CER-VD has been received.

Categorisation of study A) MySweetHeart Trial:
category A, as it entails only minimal risks and burdens.The intervention consists of a multidimensional interdisciplinary lifestyle and psychosocial intervention and no medicinal product will be given.B) MySweetHeart Cohort: category A as it entails only minimal risks and burdens.

Competent Authorities (CA)
Not applicable

Ethical Conduct of the Study
The study will be carried out in accordance with the prot ocol and with principles enunciated in the current version of the Declaration of Helsinki, the guidelines of Good Clinical Practice (GCP) issued by ICH, in case of medical device: the European Directive on medical devices 93/42/EEC and the ISO Norm 14155 an d ISO 14971, the Swiss Law and Swiss regulatory authority's requirements.

Declaration of interest
The investigators declare no conflict of interest.

Patient Information and Informed Consent
The investigat ors will explain to each participant the nature of the study, its purpose, the procedures involved, the expected duration, the potential risks and benefits and any discomfort it may entail.
Each participant will be informed that the participation in the study is volunt ary, that she may withdraw from the BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.3 2024; BMJMED , et al.

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study at any time, and that withdrawal of cons ent will not affect her subsequent medical assistance and treatment or that of her child.Each participant will be provided with an information sheet and a consent form describing the study and providing sufficient information to make an informed decision about their participation in the study.The formal consent of a participant, using the approved consent form, will be obtained before the participant is submitted to any study procedure.The participant should read and consider the statement before signing and dating the informed consent form, and should be given a copy of the signed document.The consent form must also be signed and dat ed by the investigator (or his designee) and it wi ll be retained as part of the study records.After a potential participant has been given the information sh eet, she will have a minimum of 24 hours to consider her participation in the study.
A) MySweetHeart Trial: participants will receive for their time, effort, and travel costs CHF 250 at 6-8 weeks postpart um and CHF 200 at 1 year postpartum after the res pective assessments .Partners of GDM patients will also be recruited after agreement of the patients and will receive CHF 50 at 1 year postpartum as compensation for their time, effort, and travel costs.

B) MySweetHeart
Cohort: participants will receive CHF 100 as compensation for their time, effort, and travel costs.

Participant privacy and confidentiality
The investigat ors affirm and uphold the principle of the participant's right to privacy and that they shall comply with applicable privacy laws.In particular, anonymity of the participants shall be guaranteed when presenting the data at scientific meetings or publishing them in scientific journals.
Confidentiality will be ensured by utilising subject identification code numbers to correspond to treatment data in the computer files.Furthermore, study data will be stored in a password -protected database (Secutrial) and any paper records relating to the study will be kept in a locked filing cabinet.
For data verification purposes, authorised body such as the et hics committee may require direct access to parts of the medical records relevant to the study, including participants' medical his tory.

Early termination of the study A) MySweetHeart Trial :
The investigat ors may terminate the trial prematurely according to certain circumstances, for ex ample: insufficient participant recruitment, when alterations in accepted clinical practice that make the continuation of a clinical trial unwise, or early evidence of benefit or harm of the experimental intervention.B) MySweetHeart Cohort: Not applicable 2.9.Protocol amendments Substantial amendm ents are only implement ed after approval of the CE C respectively.Only the PI and team of co-investigators are allowed to provide suggestions for a protocol amendment.Under emergency circumstances, deviations from the protoc ol to protect the rights, safety and well-being of human subjects may proceed without prior approval of the P I and the CE C. Such deviations shall be documented and reported to the P I and the CE C as soon as possible.All non-substantial amendments are communicated to the CEC within the A nnual Safety Report (ASR).

Background A) MySweetHeart Trial:
Our objective is to test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve the cardio-metabolic and mental health of women with GDM and their offspring.

Definition of gestational diabetes mellitus (GDM)
GDM is characterized by glucose intolerance diagnosed during pregnancy that does not fullfill the criteria for diabetes and usually resolves after delivery.The "Hy perglycemia and adverse pregnancy outcome" (HAP O) [1] study found strong associations of maternal glucose levels with increas ed birth weight and cord -blood C-peptide levels, as well as with primary cesarean delivery, pre -eclampsia and pre-term delivery.The HAPO study led to more stringent diagnostic GDM criteria and bas ed on the study results, a 75-g oral glucose-tolerance test (OGTT) at 24-28 weeks of gestation is recommended [2,3].The prevalence of GDM in the HAPO study (17.8% ) and elsewhere (10-15% in our tertiary setting at the CHUV hos pital and 10.9% in the Geneva and Basel Hospitals [4] is linked to the high prevalence of obesity and physical inactivity, as well as the new screening BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)

Morbidity of GDM and related conditions
GDM carries pre-and perinatal risk for the mother (pre-eclampsia, primary cesarean delivery, preterm delivery, hydramnios) and the child (macrosomia, neonat al hypoglycemia, birth injury, respiratory problems, hyperbilirubinemia, hypocalcemia, intensive care).It also carries long-term maternal risks such as a 30-70% GDM recurrence, a 7-fold higher 5-10 yr risk of type 2 diabetes (DM2), or an increased risk of metabolic syndrome and cardiovascular disease [5][6][7][8].E ven mild glucose intolerance in pregnancy is related to a 70% higher relative risk of cardiovascular disease over a 12 year median follow-up [7].Compared to women without GDM, women with GDM are twice as likely to develop perinatal or postpart um depression and approximately one-third of women with recent GDM develop postpartum depression [9].Postpart um depression leads to a decrease in physical activity and comfort eating, thus putting the women at higher risk of weight gain and future diabetes.It also leads to a decline in effective parenting skills, which may have negative consequences for the development of the child.Indeed, many parents of obes e childre n lack effective parenting skills that provide both a consistent structured frame and emotional support, and thus effective prevention strategies are needed.
In women with GDM, psychosocial vulnerability including low levels of social and family networks is associated with increases in adverse outcomes, especially infants' increased birt h weight [10].On the other hand, social support in women with GDM can promote diabetes self-care during pregnancy [11] and is a key factor for PA and a healthy diet and breastfeeding in the postpartum period [12][13][14].Social support is also a key factor in improving mental health during pregnancy [15].
Regarding the child, the import ance of the intrauterine and early postnatal enviro nments for metabolic programming and modifications of the epigenome is increasingly recognized [16].Within a Developmental Origin of Health and Disease (DOHaD) framework [17,18], fetal programming is the process involved in the associations between the exposure to detrimental factors during fetal life and health outcomes , particularly metabolic diseases, later in life [19].Thus, there is an independent relationship between GDM exposure with macrosomia at birth and with (central) obesity and insulin secretion in children, while the relationship with obesity in infants is more controversial and seems to relate to maternal BMI or birth weight [20][21][22][23][24]. Intraut erine exposure to GDM also doubles the risk for subsequent DM2 in offspring compared to offspring of mot hers with a high genetic predisposition for DM2, but with normal glucose tolerance during the index pregnancy [25].
Among epigenetic changes that are modified by the environment, micoRNAs (miRNAs ) are getting increasing interest.MiRNAs are single-stranded non-coding RNAs of approximately 21 -23 nucleotides in length whose main function is to inhibit gene expression by interfering with mRNA processes.MiRNAs suppress gene expression by affecting mRNA stability, targeting the mRNA for degradation, or both [26].Nearly 1,000 miRNAs have been identified in human cells with the potential to regulate the expression of about two-t hird of human mRNAs and influenc e almost all genetic pathways including metabolism [27].Animal maternal obesity and changes in diet lead t o altered expression of microRNA in offspring, influencing gene expression [26,28,29].Thus, miRNA's may have a critical role in the programming of metabolic alterations induced by in utero exposure to high fat diet.For instance, Fernandez-Twinn et al. showed a decrease in IRS -1 protein in adipose tissue of offspring of obese mice, correlated with miR-126 (which targets IRS-1) increase [30].Also, the differential effects of maternal obesity and weight loss in the periconceptional period on the hepatic insulinsignaling pathways in the offspring have been linked to alterations in 29b, miR-103, and miR-107 expression [31].
Maternal pre-pregnancy overweight and excessive gestational weight gain also predict high birth weight and adiposity during infancy [16,32].This is highly relevant, as up to 60-70% of women with GDM are overweight or obese before pregnancy [33].Maternal obesity during pregnancy is associated with increased hospital admission for cardiovascular events, increases the risk of adverse outcomes and all cause mortality in offs pring independent of confounders [34].Finally, lifestyle behavior such as a high fat diet or physical activity during pregnancy can influence offspring adiposity independent of maternal obesity [16,35].Recent evidence shows an increased risk of diabetes in partners of mothers with GDM, which is partly mediated by shared deprivation level and cultural background as well as lifestyle behavior [36].
The link bet ween maternal, child, and paternal metabolic health creates a delet erious vicious cycle in view of the huge and increasing worldwide prevalence of (childhood) obesity and subsequent metabolic problems despite national and international intervention efforts [37].

Because of the deleterious impact of GDM and lifestyle during pregnancy on the health of the mother and her offspring, it i s crucial to intervene during the critical window of the pre-, peri-and postnatal period.
Modifiable risk factors of GDM Figure 1 presents the modifiable risk factors of GDM that our planned intervention will address.Physical activity is a modifiable determinant of GDM.During pregnancy, physical activity is protective and reduces the risk of BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.3 2024; BMJMED , et al.

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GDM [38].It dec reas es insulin resistance and limits gestational weight gain by increasing energy ex penditure and altering food intake [39].Therefore, physical inactivity is a potent risk factor.Nutrition is another major and modifiable determinant of GDM.High fat consumption increases GDM risk, especially saturated fat, trans fat and cholesterol [40].Animal protein intake is positively and vegetable protein inversely associated with GDM risk [41].
Another key determinant is mental health.Higher stress exposure during pregnancy has been reported in women with GDM compared to those without [42,43].Our rec ent prospective study in 221 women showed that higher stress exposure and perceived stress were associated with increased fasting glucose levels before women knew their diagnosis [44].Psychological stress and negative life events are associated with higher salivary cortisol levels during pregnancy, which might influence glucose levels [45].On the other hand, good social support has been shown to be protective regarding mental health and depression in particular.Social support is also associated with increased PA in women who have a high risk of GDM [46].In addition, women with GDM report to have less social support [47].Prior studies having evaluated lifestyle interventions in GDM Generally, interventions in GDM aim for dietary and/or physical activity changes, focusing either on pregnancy or the postpart um (except for one research group [48,49]) and only on the mother [48,49].So far, their effects are limited and concern only few health aspects.

INTERVENTION
Dietary advic e is recommended for all women with GDM to improve glycemic control and to provide adequate nutrition [3].Of the few existing trials, almost all focussed on either low carbohydrate or low glycemic index foods, but either type of intervention did not consistently beneficially impact on glycemic values, despite some favourable impact on insulin requirement and/or maternal weight gain [50,51].A 2013 Cochrane review found insufficient evidence for strong conclusio ns about what dietary advice to give to women with GDM [52].As fat, especially saturat ed fat, is a risk factor for both GDM and DM2, decreasing animal fat intake represents an interesting novel approach [40,[53][54][55].Indeed, a higher-complex carbohydrate/low-fat diet including complex carbohydrates improved glycemic values, insulin resistance in women with GDM as well as infant adiposity [56].
Although rec ommended for GDM t reatment, guidelines do not specify the type of physical activity or its timing in regards to meal intake [3,57].Resistance and endurance exercise can be accomplished during pregnancy in the absenc e of contraindications, but motivation and compliance appear to be major limiting factors [58].A recent review concluded that physical activity may imp rove glycemic control and/or limit insulin use in women with GDM [59].Regular physical activity can als o limit pregnancy weight gain, stabilize maternal mood, and limit fetal fat mass and physiological stress responses in the offspring [35,58,60].
To date, there are no evidence-based psychological interventions for women with GDM and no int ernational guidelines addressing their psychosocial management.Rec ent research has looked at psychological interventions such as mindfulness-based eating awareness that aims at increasing awareness of inner cues, such as hunger and satiety, at identification of emotional eating and eating triggers, and at improving self-BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.3 2024; BMJMED , et al.

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acceptance.One study applied mindfulness eating and yoga exercise and reported reduced fasting plasma glucose, 2-h postprandial blood glucose (of around 0.5 mmol/l), and a reduction in HbA1c of 0.5% [61].

Postpartum management and follow -up
Due to the increased risk of persistence or development of prediabetes and diabetes, management of women with GDM in the postpartum period is essential and should focus both on regular screening and on prevention strategies.The American Diabetes Association, the American College of obstetricians and Gynec ologists and the National Diabetes Education Program recommend testing within 6-12 weeks postpartum with a one step 2hr 75-g OGTT [ 57,62,63].Due to t he low attendance rate at postpartum OGTT screening ( 34 to maximally 73% in published series) t here is a need to simplify the follow-up of women with previous GDM [64].The highest risk period for the development of DM2 is within the first 5 years after a GDM pregnancy [65].Despite this critical timeframe, there is a scarcity of RCT's in this young population [65].
Weight loss is an important predictor to prevent diabtetes in high -risk population.Thus, in the Diabetes Prevention Program DPP weight loss after GDM reduced future diabetes incidence by 16% for every kilogram lost [66].Existing large randomised studies in women after GDM lead to a decrease in weight, while the impact on diabetes incidence was controversial [66][67][68][69].
The "Diet, Exercise and Breastfeeding Int ervention" (DEB I) study [48] is the only study that started during pregnancy and continued postpartum, and was mostly delivered by phone.The proportion of women who reached their 1 year postpartum weight goal tended to be higher in the int ervention arm (37.5 vs 21.4%, p= 0.07).However, to our knowledge, no large post-GDM RCTs exist in a multi-ethnic European population.

Prevention strategies in the child
Offspring of women with GDM are at higher risk for childhood obesity.Several modifiable risk factors have been identified, such as infant feeding mode (bottle vs breastfeeding), infant sleep duration, parental reaction to regulate infant distress and (particularly nocturnal) crying, timing of the int roduction of solid food, sweetend beverage consumption, and the age of bottle weaning [70].For example, breastfeeding attenuates the increased risk of childhood adiposity that is associated with exposure to diabetes during pregnancy [71].Feeding is often used as a first res ponse to infant distress [72] and is more prevalent in mothers who eat themselves when distressed [73].Parents with overweight, obesity or diabet es may adapt controlling c hild-feeding practices and these parental control attempts may interact with genetic predispositions to promote the development of problematic eating styles and childhood overweight.A parenting skills intervention should focus on these factors, provide anticipatory guidance and teach parents how to identify and respond appropriat ely to infant cues and distress to positively influence self-regulatory capacities, well-being and the developing c ontrol of the infant's food intake in order to avoid eating in the absence of hunger [74,75].

Development of a multidimensional interdisciplinary lifestyle intervention
Given that single risk factor interventions have shown limited efficacy, multidimensional approaches targeting both the mother and the child and including the partner could be more efficient considering the complex multifactorial origin of GDM and its transgenerational importance [76] (Figure 1).Indeed, a multidimensional interdisciplinary and psychosocial approach integrating the above mentioned modifiable risk factors in a concerted and individually adapted fashion could help to improve t he treatment of GDM and to reduce long-term complications [77].Such an approach would need to be started in pregnancy and continue postpartum.
In summary, the multifactorial origin of GDM, and the close link between the different risk factors as well as between maternal, child, and paternal health and t he critical window of t he perinatal period call for a multidimensional interdi sciplinary lifestyle and psychosocial interventioninterdi sciplinary that spans through pregnancy and the postpartum period and focuses on the health of the mother and her child .

B) MySweetHeart Cohort:
Cardio-metabolic effects of GDM within a DOHaD framework Maternal hyperglycemic disorders are associated with offspring's fetal c ardiac and vascular structural and functional alterations.For instance, it is well known that offspring of T1/ T2DM mothers are at increased risk of congenital cardiac malformations and cardiac hypertrophy [78,79].In a retrospective study of 92 offs pring of 87 diabetic mothers conducted in Lausanne, we obs erved that 5 neonates had congenital heart disease and 12 had ventricular hypert rophy [78].There is also growing evidenc e that maternal hyperglycemic disorders may be involved in the "fetal programming" of obesity and of metabolic disorders in their offspring [80].Within a Developmental Origin of Healt h and Disease (DOHaD) framework [81,82], fetal programming is the process involved in the associations between the exposure to det riment al factors during fetal life and health outcomes later in life [83].Fetal programming is suspected to be involved in the development of cardio-metabolic disorders, such as elevated blood pressure, coronary heart diseases or DM, notably through epigenetic mechanisms [81,82].Despit e recent and large growth in this research area, studies are needed to better objectively characterize both early life exposure and cardio-metabolic outcomes [84].
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)   2: Hy pothetical and highly -simplif ied causal relationships between gestational diabetes mellitus (GDM) and cardio-metabolic disorders.Two pathway s can be hy pothesized: 1) a direct effect of GDM on offspring's cardio-metabolic disorders; 2) an indirect eff ect through the mediator large f or gestational age (LGA).It means that if LGA was prev ented, part of the eff ect of GDM on cardio-metabolic disord ers wo uld be p rev ented.Sev eral conf ounding f actors (such as maternal obesity , weight gain during pregnancy , smoking, socio-economic status, or f amily history of cardio-metabolic diseases) hav e to be accounted f or.
Several epidemiologic studies suggest that intrauterine environment of women with DM contribute to long term risk of met abolic diseases and intergenerational transmission of cardio-met abolic risk [80].For example, adult offspring of women with DM during gestation have increased risk of overweight/obesity [85][86][87][88], metabolic syndrome [85,87], T2DM [89], or pre-diabetes [89].Exposure to maternal impaired glucose tolerance or DM during fetal life is associated with large fetal fat mass [90] and overweight/obesity in childhood [91].A large sibling study shows that the association bet ween maternal DM and offspring BMI was most likely due to in utero exposure to hyperglycemia and not to confounding by shared familial characteristics [92].It was also shown that offspring who had been exposed to maternal DM during fetal life exhibit higher prevalence of impaired glucose tolerance and markers of insulin resistance in childhood and adolescence [93,94].One study shows that LGA offspring of GDM mothers are at great er risk of developing metabolic syndrome disorders compared to non -LGA offspring of GDM mothers [95].
LGA may be therefore a mediator on the causal pathway between mat ernal hyperglycemic disorders, including GDM, and cardio-metabolic disorders, and hence could be a clinical marker of fetal programming (Figure 2).The association between maternal hy perglycemic disorders and LGA seems to be due to the inc rease in fetal insulin production in response to the increased transplacental transfer of mat ernal glucose [96,97].In the HAPO study, maternal hyperglycemia and fetal hyperinsulinism were associated with high birth weight.Intrauterine exposure to high maternal blood glucose has also been associated with greater lean mass and adiposity among prepubertal offspring [98].
During fet al life, maternal diabetes is associated with fetal hyperinsulinism responsible of structural and functional change affecting mostly the liver and the cardiovascular system.The liver is the major metabolic organ, considered as the metabolic brain and responsible for the distribution of the placental resources [99].Recent studies have shown that mac rosomic offspring had impaired liver blood perfusion that contributes to the dysregulation of the fetal growth [100][101][102] and that differential perfusion of the fetal liver modified hepatic metabolic function and size [99].Studies indicate that the liver is enlarged in fetuses of T1/ T2 DM mothers [103,104].Furthermore, and similarly, the fetal heart response to hyperinsulinisim is the development o f an asymmetrical hypert rophy predominant at the septal wall.Cardiac hypertrophy res ults rarely in major cardiac outflow obstruction.Usually, by 6 months of age, it has totally resolved without further long -term functional repercussion [105].

Lack of data on the effects of GDM on offspring's cardiovascular health
Most studies on the effect of maternal hyperglycemic disorders were conducted among mothers with T1/ T2DM, not among mothers with GDM, and with an emphasis on the effects on offspring's metabolic outcomes rather than on offspring's cardiovascular health.It is also unknown whether treatment of GDM is effective to reduce long-term risk of offspring's metabolic and CV D risk [80,106,107] and the new definition of GDM calls also for the conduction of further studies on the impact of GDM on offspring's cardiovascular health.To study t he early development of at herosclerosis and pathogenesis of CV D, it has become central to assess surrogate markers of CVD such as increased cardiac mass (left ventricular mass index; LVMI) [108] and of subclinical at herosclerosis (assessed trough carotid intima-media thickness; cIMT) [108,109].These markers have been used extensively in studies in children and young adults with CVD risk factors [108][109][110].However, to our knowledge, the effects of GDM on fetal and early neonatal offspring' s cardiovascular health, and in particul ar on such surrogate markers, have never been studied.

Preclinical Evidence Not applicable
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Clinical Evidence to Date A) MySweetHeart Trial:
We have conducted several pilot studies that form the base for the rationale of the multidimensional intervention.
(1) Our study on stress and GDM [44] confirmed the rationale to int egrate a psychosocial part in the intervention, as we showed for the first time that higher stress exposure and higher perceived stress were associated with higher fasting glucose levels before women knew their diagnosis.
(2) A clinical GDM cohort study of 322 patients that we started in 2013, helped us to (1) assess the prevalence of overweight (27%) and obesity (22%; which is 3-fold higher compared to women of the large Co-Laus cohort in the same city, but lower t han in other studies, (2) to assess the mean gestational weight gain, the postpartum weight retention and symptoms of postpartum depression.
(3) Two focus groups of our GDM patients suggested feasibility (home-based exercises, need for support) and identified barriers (having young children, lack of risk perception, anxiety) of our planned intervention.(4) We also performed a small postpartum physical activity study over 3 months in which women in the intervention arm significantly increased their reported physical activity (p=0.03) and lost 2.3 ± 1.4 kg more weight (p = 0.1) than women in the control arm.

B) MySweetHeart Cohort:
We have conducted a study to insure that the measurement of carotid intima-media thickness (CIMT), our primary outcome, was feasible in young non-sedated infants (Mivelaz et al, under review).This study conducted among 81 infants less than 1 years of age confirmed that CIMT was measurable wit h a high inter-observer reliability (coefficient of variation: 5.9%).

Explanation for choice of comparator (or placebo) A) MySweetHeart Trial:
The comparis on group will receive treatment as usual (not placebo), which is based on the current guidelines of the American Diabetes Association [2] and the Endocrine Society [3] (see section 8.2.2. for more details).

Risks / Benefits A) MySweetHeart Trial:
For the participants allocated to the intervention group, there will be a potential direct benefit from a multidisciplinary lifestyle and psychosocial intervention that may be superior to the current treatment as usual by leading to reduced weight and less symptoms of depression.A potential risk is the occurrence of early contractions due to intense physical activity.In order to monitor and mitigate this potential risk, patients will be closely supervis ed by a physician and physiotherapist.In case of early contractions, participants will be requested to reduce or stop their physical activity.
For the participants allocated to the control group, there are no anticipated risks or benefits.

B) MySweetHeart Cohort:
There are no anticipated risks or benefits.If cardiac anomalies are identified during cardiac echography (but not revealed by the routine prenatal ultrasound), the parents will be informed and counselled by the paediatric cardiologist in the same manner as would be done if the finding had been detected on usual prenatal screening.

Justification of choice of study population
This study aims at investigating pregnant women (aged >18 years) with GDM or without GDM and their offspring.The choic e of pregnant women is linked to the health problem under investigation, GDM being a condition only occurring during pregnancy.

STUDY OBJECTIVES A) MySweetHeart Trial: A4.1) Overall Objective
To test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve the cardio-metabolic and mental health of women with GDM and their offspring.

A4.2) Primary Objective
To test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention in women with GDM to improve 1) their metabolic (decrease in mat ernal weight between 24-32 weeks gestational age and 1 yr postpart um) and 2) their mental (decrease in maternal symptoms of depression during the same time period) health.

A4.3) Secondary Objectives
To test the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve other cardio-metabolic and mental health markers in women with GDM and their offspring.
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A5.4. Safety Outcomes
A potential risk is the occurrence of early contractions due to intense physical activity.In order to monitor and mitigate this potential risk, patients will be closely supervised by a physician and physiotherapist.In case of early cont ractions, participants will be requested to reduce or stop their physical activity.Any information related to safety issues will be recorded in the CRF.

Recruitment
All pregnant women attending their ant enatal appointment at the policlinique at the CHUV for their routine screening for GDM at around 22-31 weeks will be pre-informed about the study (flyer).We will recruit 200 women with GDM and 100 women without GDM.
Women with GDM: Pregnant women who received the diagnosis of GDM are referred to the GDM consultation at the CHUV (expected N = around 250 GDM patients/year, 2/3 are referred from privat e obstetricians, the rest from the CHUV).In addition, women with GDM who are followed up by private diabetologists in the canton Vaud (N = around 150 GDM patients/year) will be invited to participate following a similar procedure.Following their first clinical appointment, the study coordinator will explain the study and give the information sheet to the patient.Once the patient has had time to reflect (min.24 hours ) and signed the consent form, she will be included in the study.Partners of women wit h GDM will also be invit ed to participate, if the patient agrees that her partner is contacted.
Women without GDM: All pregnant women attending their antenatal appointment policlinique at the CHUV will be invited to participat e after their routine screening, once GDM has been excluded.The study coordinator will explain the study and give the study information sheet to the patient.Onc e the patient has had time to reflect (min.24 hours) and signed the consent form, she will be included in the study.
Women with GDM participating in MyS weetHeart Trial will receive for their time, effort as well as the fees for their frequent travels CHF 200 during the prepartum period and CHF 200 during the postpart um period.Partners of women with GDM will receive CHF 50 as compensation for their time and effort.Women without GDM participating in MySweetHeart Cohort will receive CHF 100 as compensation for their time and effort.

Assignment to study groups A)
MySweetHeart Trial: Block 1:1 randomisation will be used.A list of blocks of four will be generated in advance and numbered opaque envelopes will be prepared by the data manager.Once the patient has signed the informed consent form, the study coordinator will open the envelopes and communicate the group allocation to the patient (allocation concealment).The sequence of randomisation blocks will be concealed over the course of the study.

Criteria for withdrawal / discontinuation of participants A) MySweetHeart Trial:
Participants will be excluded from the study if they wish to withdraw.

B) MySweetHeart Cohort:
Participants will be excluded from the study if they wish to withdraw

Administration of experimental and control interventions
This section is applicable only for MySweetHeart Trial

Experimental intervention
The multidimensional interdisciplinary lifestyle and psychosocial intervention will be offered on top of usual care (8.2.2).It will consist of individual sessions (face-to-face or telephone contact) with different members of the interdisciplinary team (dietician, physiotherapist, clinical psychologist or coach) and t wo group sessions.It will BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)  1).
The int ervention group will have the following key components in addition to the usual care of the cont rol group: Prenatally, 2 physiotherapy and 2 additional dietician consultations, 1 interdisciplinary group session.Based on the patients' context and capacities, individually tailored treatment goals will be established (see Table 4).At study begin, and at 6-8 weeks, patients will be screened for depression.According to a stepped care approach (based on the patient's EPDS score), individual sessions with the clinical psychologist will be offered (see Table 3 for more det ails).Postnatally, patients will have 4 interdisciplinary individual consultations (dietician, psychologist; physician when needed) focusing on the health of the mother and her offspring, and 1 interdisciplinary group sessions.Throughout the pregnancy and up to 1 year postpartum, patients will be accompanied and support ed by a coach (to monitor adherence to t he intervention, provide support and teach strategies to work towards the individual goals).During pregnancy, the coach will have 10 min of weekly contact (by phone and/or face to face if patients come for a visit) and tailor the individual intermediate goals to patients' context and capacities in accordance wit h the respective specialists.During the first year postpartum, the coach will have contact with the mother twice monthly.To increase social support, partners will be invited to attend individual and group sessions during both the prepartum and postpartum period.If partners are unable to attend those sessions, then we will offer a Skype or telephone cont act.In addition, small peer support groups will be formed during the interdisciplinary group sessions.
To improve the mental health of participants, the coach will be taught to perform routine screening based on self-report questionnaires and will be trained in cognitive behavioural, mindfulness and motivational strategies, with regular supervision by a clinical psychologist.Participants reporting elevated symptoms (EPDS score of psychopathology on the self-report questionnaires will receive systematic support by the clinical psychologist based on a stepped care approach.Patients who r equire a psychiatric evaluation including psychotropic medication will be referred to the Psychiatrie de Liaison at the CHUV. Information about the interplay bet ween mental health, lifestyle behaviour and GDM as well as the link bet ween maternal GDM and the future risks for the mot her and the offspring (to improve risk perception) are part of the educational approach.Adherence to the intervention will be enhanced through personal cont act based on motivational interviewing and therapeutic patient education.
During the first postpartum year, an educational approach will also be used wit h the mother (and her partner) to improve their cardio-metabolic and mental health by working on the objectives for their infants (see Table 4).
The follow-up will be provided at the Gestational Diabetes Clinic at the CHUV for all patients that are referred there for clinical care.If the patient is followed by a diabetologist outside of the CHUV, the care that is part of the usual clinical follow-up will be provided by the diabetologist, but the on-top intervention parts and the assessments will be performed at the CHUV.We will ensure close collaboration with the obstetricians, paediatricians, and existing health care networks that form part of the patients' usual clinical c are.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)   Based on the EPDS score, patients will be seen for individual sessions by a clinical psychologist integrated in the team using a stepped care approach (NICE, 2009) with supervision of the Psychiatry Liaison Service.The focus is on prevention and early intervention, with a one-off session offered in case of mild symptoms, and more in case of moderate symptoms (EPDS=10+), or moderate to severe symptoms (EPDS=13+).

Adherence: Assessment and treatment of problems:
In case of problems with adherence interfering with adequate metabolic control, members of the multidisciplinary team may also ask for a clinical assessment by the team clinical psychologist.No specific intervention

Control Intervention
Usual clinical follow-up and treatment is based on the current American Diabetes Association [2], the Endocrine Society guidelines [3], and the NICE [111,112] guidelines.
Patients will be first seen at 24-32 weeks of gestation by a physician and/or a nurse practitioner that follow them up to delivery.During the first visit, patients learn about GDM, how to perform self-control of blood glucose 4x/day (fasting and postprandially) and are encouraged to increase physical activity [113].They have one appointment with a registered dietician to receive individualized dietary advice to avoid soft drinks and limi t added sugar, s weet products and juices.If glucose values remain above t argets, twice or more during a 2 week period [113], metformin or insulin treatment is installed depending on glucose values (e. g. insulin for high values), patient preferenc e, and the evaluation of the clinical healt h care professional.Patients then undergo a 75 g OGTT at 6-8 weeks postpartum and are seen afterwards by the physician or nurs e practitioner and a dietician jointly to discuss results and further management.Patients then resume us ual care by their health care provider outside of the clinic.A screening for glucose toleranc e by fasting glucose and HbA 1c is recommended at 1 year postpartum, and then regularly every 1-3 years [2].
This usual clinical follow-up will be provided at the Gestational Diabetes Clinic at the CHUV for all patients that are referred there for clinical care.If the patient is followed by a diabetologist outside of t he CHUV, the usual clinical follow-up will be provided by the diabetologist, but the assessments will be done at the CHUV.
Patients with an EPDS score of at least 13 who require a psychiatric evaluation including psychotropic medication will be referred to the Psychiatrie de Liaison at the CHUV.

Dose / Device modifications
Not applicable.

Compliance with study intervention
Patients will have regular contact with t he coach who will monitor their adherence to the intervention.Brief summaries of the number of clinical appointments and t elephone contacts will be kept, as well as the number of missed appointments and their reasons.
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Data Collection and Follow -up for withdrawn participants
Withdrawn participants of the RCT will be contacted by telephone by the coach at 1 year postpartum with the aim of measuring the primary outcomes.

Trial specific preventive measures
Not applicable.

Concomitant Interventions (treatments)
All concomitant treatments will be noted in the CRF.If clinic ally indicated, patients can attend external sessions of psychotherapy during the trial.Participation in structured physical activities such as sports clubs or other physical activity group sessions will be also recorded.Patients can also take any medications, vitamins and micronutrients as clinically indicated.

Study Drug / Medical Device Accountability
Not applicable.

Return or Destruction of Study Drug / Medical Device
Not applicable.

Study flow chart(s) / table of study procedures and assessments
See Table 1 and 2, and sections 5.1.and 5.2.

Assessments of outcomes
Written standard operating procedures (SOPs) will be provided for the following outcomes: -height and weight (mother and infant) -bioimpedance (mother and infant) -skinfolds (mother and infant) -Chester step test -Jamar dynamometer -blood sampling (maternal and cord blood) -fetal ultrasound

Assessment of primary outcome A) MySweetHeart Trial:
Our primary outcomes will be differences bet ween the int ervention and cont rol group in (1) the decreas e in maternal weight and (2) decrease in maternal symptoms of the Edinburgh Postnatal Depression score at 1 year postpart um, both of which will be assessed by research staff blinded to the group allocation.Maternal weight will be meas ured by using a calibrated Seca scale.Depression symptom score will be assessed using a validated self-report questionnaire (Edinburgh Postnatal Depression Scale).

B) MySweetHeart Cohort:
Primary outcomes will be the surrogate markers of CV D at birth [left ventricular mass index (LVMI) and subclinical atherosclerosis (carotid intima-media thickness; cIMT)].
A neonate echocardiography will be performed 2-4 days after birth (before the mot her and the newborn leave the clinic) by two experienced ultrasonographers (Dr N. Sekarski and Dr S. Di Bernado) blinded to the mat ernal glycemic status and to the fetal echocardiogram.Echocardiography will be performed on a Philips iE33 echocardiogram with a S8-3 or S5-1MHz transducer, digitally recorded (Xc elera, Philips) and analyzed off-line.Standard echocardiography including M-mode, color and spectral Doppler according to the ASE will be performed [114,115].Measurements will be performed according to the standard of the ASE [114,115].including: 1) right and left atrial chamber sizes and volumes; 2) LV size, volume and function; 3) LV mass; 4) LV and RV systolic and diastolic function.Z scores based on BSA calculated by the Haycock formula will be used to express these measurements [116][117][118].
During cardiac echocardiography, carotid ultrasound will be performed 2-7 days after birth (before the mother and the newborn leave the clinic) by two experiment ed ultrasonographers (Dr N. Sekarski and Dr S. Di Bernardo) blinded to the maternal glycemic status.Carotid IMT measurement will be performed on a Philips iE33 echocardiograph (Philips Medical, Net herland) with a L 11-5 MHz high-resolution linear array transducer, recorded on a digital system (QLab, Philips Medical Netherlands ).Image acquisition will be done according to BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.3 2024; BMJMED , et al.

Quansah DY
the standard of the American Heart Association (AHA) Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young [109].Image analyses will include: 1) farwall cIMT; 2) calculation of t he mean of maximal c IMT measurements (diameter of carotid art ery); 3) calculation of carotid stiffness.Measurements of cIMT will be expressed in mm as mean +/ -SD and compared with normal cIMTs [119,120].

Assessment of secondary outcomes A) MySweetHeart Trial:
Maternal secondary outcomes will be (1) lifestyle behaviours (carbohydrate and fat intake, eating behaviour, breastfeeding, feeding behaviour, physical activity, sleep), aerobic fitness and strength, body composition (total and regional fat mass), cardiometabolic laboratory biomarkers (2) other mental health indicat ors (anxiety, wellbeing, perception of social support, parenting stress); during the perinat al and postpartum period (see above under outcomes and in the assessment table for the exact timings).
Offspring secondary outcomes are (1) cardio-metabolic laboratory biomarkers at the time of delivery , body composition (BMI, total fat mass) at birth, 6-8 weeks pp and at 1 yr of age; and (2) mental healt h indicators (selfregulation, sleep quality and quantity) at 1 yr of age.
More details on assessments are provided in Table 2.

A1) Maternal outcomes:
A1.1) Lifestyle behaviours: Carbohydrate and fat intake will be measured by the Food Frequency Questionnaire, eating behaviour by the French Intuitive Eating Scale, breastfeeding by self-report with a focus on duration and exclusiveness.Physical activity will be measured using an accelerometer t hat is worn during one week on the wrist (GeneActiv®).Sleep will be measured using the Pittsburgh Sleep Quality Index .A1.2) Aerobic fitne ss will be assessed using the Chester step test with VO2max estimation and grip strength using a Jamar dynamometer.A1.3) Body composi tion measures include bioelectrical impedance analysis using a 4-polar single frequency devic e (RJL Systems, Model 101A; Detroit, MI, USA), the sum of four four skinfolds (triceps, biceps, subscapular and suprailiac) by triplicate measures using a Harpenden calipers (HSK -B I, British Indicators, UK) as well as Dual-Energy-X-Ray absorptiometry (Lunar®).A1.4) Cardiometabolic laboratory variables include HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, HbA1C, insulin, glucose, indices of insulin resistance and insulin secretion, gamma-GT, B12 vitamin, ferritine, free fatty acids, and miRNA.Further, a sample of blood will be kept for future potential analyses.All samples will be managed and stored within the EDM biobank.

A1.5) Additional mental health indicators:
Anxiety will be measured wit h the Anxiety subscale of the Hospital Anxiety and Depression Scale; depression with the Edinburgh Postnatal Depression Scale and Whooley questions.Well-being will be assessed with the WHO Well-B eing Index, social support with the Medical Outcomes Study Social Support Survey-short form, and parenting stress with the Parenting Stress Scale-short form.
(2) Offspring outcomes: A2.1) Cardio-metabolic laboratory biomarkers: A cord blood sample will be collected at the time of delivery.The following variables will be meas ured: HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, HbA1C, c-peptide, insulin, creatinine, uric acid, glucose, hs -CRP, gamma-GT, B12 vit amin, and ferritine and miRNA.Further, a sample of blood will be kept for future potential analyses.All samples will be managed and stored within the EDM biobank A2.2) Body composition measures include height, weight using standardized tools for babies, bioelectrical impedance analysis using a 4-polar single frequency device (RJL Systems, Model 101A; Detroit, MI, USA) and the sum of four four skinfolds (triceps, biceps, subscapular and suprailiac) by triplicate measures using a Harpenden calipers (HSK-BI, British Indicators, UK).

A2.3) Mental health indicators:
Self-regulation will be measured with the Difficult Child subscale of the Parenting Stress Index-Short form.Sleep quality and quantity will be measured using the Brief Infant Sleep Questionnaire.

B) MySweetHeart Cohort:
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B.1)
A fetal ec hography will be performed bet ween the 30th and 34th week of gestation by two experimented ultrasonographers (Dr Y van Mivelaz and Dr Y van Vial), blinded to the maternal glycemic status, using a Voluson E8 Expert (General Electric Medical Systems, ZIPF, Australia) equipped with a 3-5 MHz convex array sector transduc er.A systematic echography will be conducted to detect structural and functional anomalies following international recommendations [121,122].Anthropometric measurements and fetal well -being parameters will be measured.Then, a detailed echocardiography of the fetal liver, cardiovascular system and of the maternofetal circulation will be conducted including bidimensional (2D), M-Mode (M), Doppler (D) and tridimensional (3D) imaging of the following structures: cardiac 4 chambers (2D), RV and LV short axis (2D, M), tricuspid, pulmonary, mitral and aortic valve (2D, D), lateral and medial mitral annulus, and tricus pid annulus (2D, D), umbilical vein, ductus venosus, patent ductus arteriosus, aortic isthmus, umbilical arteries and maternal uterine arteries (2D, D) and liver (2D, 3D).This will allow the assessment of the LV posterior wall and septal thickness, the LV mass [122], the LV and RV systolic and diastolic function, the cardiothoracic ratio, the placental and fetal vascular resistances, the cardiac output and liver volume.Data will be digitally stored to allow off -line analyses.Measures will be expressed as z-scores based on gestational age to allow comparison between fetuses.

B.2)
A cord blood sample will be collected at the time of delivery.The following variables will be measured: HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides, HbA1C, c -peptide, insulin, creatinine, uric acid, glucose, hs-CRP, gamma-GT, B 12 vitamin, ferritine, free fatty acids, and miRNA.Further, a sample of blood will be kept for future potential analyses.All samples will be managed and stored within the EDM biobank .

Assessment of other outcomes of interest
Not applicable.Note that part ners' variables will be body weight and height, eating behaviour and mental health symptoms (anxiety, well-being, perception of social support, parenting stress ).These will be assessed in the same manner as described above for the women with GDM.9.2.4.Assessment of safety outcomes 9.2.4.1.Adverse events See section 5.4 9.2.4.2.Laboratory parameters Laboratory results will be monitored and those with clinical relevance will be considered.Should action be required, the information will be transferred to the treating physician.

Vital signs
As part of the clinical routine, blood pressure and heart rate will be measured in a sitting position at the beginning and end of the study as well as during the medical pregnancy visits.

Assessments in participants who prematurely stop the study
Participants who are withdrawn from the study prematurely will not be followed up.

Procedures at each visit
Depending on the group (non GDM; GDM-c ontrol; and GDM-intervention), the number and nature of the visits will be different (see Table 1: Overview of visits for the 3 study groups and Table 2: Assessments and events for the 3 study groups).The clinical visits for participants with GDM are detailed in Table 2.

Pre-screening visit
The primary purpose is to recruit pregnant women followed up in the maternity policlinic at the CHUV.As part of the normal pregnancy follow-up at the policlinic, each pregnant woman comes between weeks 22-31 of gestation for GDM screening (fasting glycemia).A fter this visit, members of the research team will meet them to briefly present the study and give the preliminary information sheet.This first contact with potential participants allows us to evaluate their capacity to understand our explanation and their interest and motivation to take part in the study.Depending on the result of the fasting glycemia, different options will arise: 1) In case of normal fasting glycemia, the research staff will contact them by phone the same day, to ask them if they accept to participate as non-GDM control participants (after having had time to read the preliminary information sheet ).If they accept, we send the information/consent letter, and the first visit is planned at the same time as the next normal pregnancy follow-up visit (usually within 2 weeks following t he fasting glycemia measurement).
2) In case of high fasting glycemia, the patient will receive a phone call from the policlinic, with an invitation for the oral glucose tolerance testing (routine diagnostic procedure for GDM).In case of normal OGTT, the same recruitment procedure as for the normal fasting glycemia will be applied.In cas e of abnormal OGTT, the patient BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJMED doi: 10.1136/bmjmed-2023-000588 :e000588.3 2024; BMJMED , et al.Quansah DY will be t rans ferred to the gestational diabetes cons ultation at the Maternity Department.Rec ruitment will be done there along with GDM patients that are referred from obstetricians and diabetologists outside the CHUV .

Recruitment (24-32 weeks of gestation); Visit 1 and Baseline asse ssment (24-32 weeks of gestation)
(a) Women with GDM: They will be informed about the study and receive the participant information sheet.When they come back a few days later to attend their first appointment with the dietician, they will report their interest to participate or not in the study.Once they have signed the consent form, baseline assessments will be carried out, including measurements of weight and height, validated self-report questionnaires, tests of aerobic fitness and strength, body composition (skinfolds (callipers), and bioimpedance (see Table of outcome measures and assessments) as well as 3 measures of blood pressure.If t he patient agrees, their part ners will also be informed about the study and invited to participate using a separate info rmation sheet and cons ent form.Onc e he has signed the consent form, research staff will measure his weight and height and ask him to complete validated self -report questionnaires.The medical assistant will draw an additional 31 ml of maternal blood during the planned blood sampling (no extra puncture).
Women recruited by diabetologists outside the CHUV will be informed about the study by the diabetologist, receive the participant information sheet and asked if they agree to participate and be contacted by the study investigator.If they agree to participate, a visit for the baseline assessment will be scheduled.

(b) Women without GDM:
They will be informed about the study and receive the participant information sheet.Once the women have agreed to participate and signed the consent form, the nurse will tak e an additional 31 ml during the planned blood sampling (no extra puncture).These tubes will be used for the meas urement of cardio-metabolic biomarkers.After the pregnancy control visit, the research assistant will take 3 measures of blood pressure, measure height and weight, ask the participant to complete the self-report questionnaires (see Table of outcome measures and assessments), and for her pregravid weight.

Visit 2 (30-34 weeks prenatal)
This visit applies to all participants.During this visit, a fetal utras ound, including cardiac structure and function and liver size will be performed by the obstetricians and fet al cardiologist of the study.The res earch assistant or nurse will also take 5 measurements of blood pressure.

Visit 3 (during childbirth)
This visit applies to all participants.During delivery, an additional 3 ml will be drawn from the venous line previously installed (no venipuncture) at the entry in the delivery room (normal or elective caesarean surgery).After delivery, blood will be drawn from the cord following clamping.

Visit 4 (2-7 days postpartum)
This visit applies to all participants.Whilst the woman is still hospitalised after delivery, an echocardiography and an c IMT measurement will be performed on the baby.The investigations will be carried out by the pediatric cardiologists of the study.Three maternal blood pressure readings and maternal weight will be taken.

Visit 5 (6-8-weeks postpartum)
This visit does not apply to women without GDM.Women with GDM whilst attending a clinical appointment will be asked to complete a series of validated self-report questionnaires, their height and weight will be measured.They will undergo a bioimpedanc e assessment and skinfolds measurements (using callipers).10 ml extra blood will be drawn during the planned clinical blood sampling.Weight, height and skinfolds of their infant will be assessed.

Final visit 6 (1 year postpartum)
This visit does not apply to women without GDM.Women with GDM will be asked to complete validated selfreport questionnaires, and will undergo tests of physical fitness and strength, skinfolds, bioimpedance and DE XA (see Table of outcome measures and assessments).31 ml extra blood will be drawn during the planned clinical blood sampling.Weight, height and skinfolds of their infant will be assessed.For the partners of women with GDM, the research staff will measure their weight and height and ask them to complete validated selfreport questionnaires.The primary objectives of the study are to test the effect of a multidimensional lifestyle and psychosocial intervention in women with GDM to improve 1) their metabolic (decrease in maternal weight bet ween 24-32 weeks gestational age and 1 year postpart um at the end of the study) and 2) their mental (dec reas e in EPDS depression score during the same time period) health.The null hypotheses are that there will be 1) no differenc e in the reduction of weight and 2) no difference in the reduction of the EP DS depression score between the intervention and the control arm between the study inclusion and the study end.

B) MySweetHeart Cohort:
The primary objectives of the study are to assess the effect of GDM on the surrogate markers of cardiovascular disease (CV D) at birth (left ventricular mass index and subclinical atherosclerosis).The null hypotheses are that there are 1) no difference in mean LVMI and 2) not difference in c IMT between children of women with GDM and children of women without GDM.

A) MySweetHeart Trial:
We have computed t he sample size based on the expected difference in primary outcomes (change in mat ernal metabolic and mental health, i.e., change in weight and in symptoms of the Edinburgh postnatal depression score) between women with GDM allocated to the control and the int ervention group.Sample size estimations were performed based on our pilot data.
Regarding maternal weight, we assumed a weight reduction of 2.5 kg [SD: 5] between study inclusion at 24-32 GA, after GDM diagnosis and 1 year postpartum in women alloc ated to the control group compared to a weight reduction of 5 kg [SD: 6] in women allocated to the intervention group.The required sample size is 78 women in each study group to have a statistical significant difference with a power of 80% and an alpha-level set at 0.05 (two-sided).This sample size is also sufficient to observe statistical significant differences in the reduction in the Edinburgh Postnatal Depression symptoms score, if we assume that the reduction in depression score between the above mentioned two time points is 2 [SD: 4.3] in women allocated to the control group and 4.0 [SD: 4.4] in women allocated to the intervention group.
Assuming a lost to follow-up of maximum 20%, we will include 100 women in the control and 100 in the intervention group.

B) MySweetHeart Cohort:
We have computed the sample size based on the expected difference in primary outcomes (LVMI and cIMT) between children of women with GDM and children of women without GDM.Assuming that LVMI will be 30.0g/m2.7 [SD: 4.5] in children of mothers without GDM [123] compared to 32.0 g/m2.7 [SD: 4.5] in children of women with GDM, the required sample size is 80 women with GDM and 80 women without GDM to have a statistical significant difference with a power of 80% and an alpha-level set at 0.05 (two-sided).This sample size is also sufficient to observe statistical significant differences in cIMT at birth if we assume that cIMT at birth is 0.44 mm [SD: 0.04] [108] in newborn of women without GDM and 0.42 mm [SD: 0.04] in newborn of women with GDM.We do not expect to have a substantial lost to follow-up between inclusion and delivery.Nevertheless, in the worst case scenario, we could lose ~20% of the participants.Therefore, we will include 100 pregnant women with GDM (corresponding to the 100 women of the control group of the trial) and 100 women without GDM.

Statistical criteria of termination of trial A) MySweetHeart Trial:
Given this is a low risk trial with many important exploratory secondary outcomes, there are no preplanned BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) We will analyze the complete dataset of the intervention and control group of patients with gestational diabetes.In a first step, the population will be analysed as intention to treat.In a second step, we will also perform a per protocol analyses.Subgroup analyses will be performed according to weight status, mental health status (at risk vs not at risk patients), ethnicity, prediabetes status at the intial postpartum evaluation (6-8 weeks pp) as well as sex (for the children).

B) MySweetHeart Cohort:
We will analyze the complete dataset of patients with GDM and without GDM.

Primary Analysis A) MySweetHeart Trial:
For the primary analyses, differences in the changes in maternal weight and the EPDS depression symptoms score between inclusion after GDM diagnosis and 1 year postpart um at the end of the study between the 2 groups will be analyzed using linear regression analysis.Analyses will be adjusted for the respective baseline values if there are differences between arms.Variables will be transformed if residuals are not normally distributed.We will include potential confounding variables, if necessary.The potential confounding variables are maternal age, sex of the children, pre-, peri-and early postnatal conditions/complications, and socioeconomic status where applicable.Analyses will be conducted with STATA 14.0.

B) MySweetHeart Cohort:
The primary hypothesis is that mean LVMI, respectively cIMT, is larger in children of women with GDM than in children of women without GDM.This hypot hesis will be tested using linear regression analyses, GDM being the exposure, LVMI (respectively cIMT) being the outcome, and with adjustment for potential confounding factors (i.e., maternal obesity, weight gain during pregnancy, smoking, socio-economic status, or family history of cardio-metabolic diseases).Regression coefficient will be reported with 95% confidence interval.Analyses will be conducted with STATA 14.0.

Secondary Analyses A) MySweetHeart Trial:
For secondary outcomes, the same type of statistical analyses will be conducted as for the primary outcomes.The analyses will be performed for differences in changes between groups and differences between groups at different time points (baseline at inclusion, delivery, 6-8 weeks and 1 year postpartum) in maternal metabolic health outcomes, maternal mental health outcomes and offspring metabolic and ment al health outcomes that will be tested using linear regression analysis.Associations between outcomes will also be tested using linear regression analyses.
We will also compare the proportion of patients meeting guidelines for gestational weight gain and weight retention at 1 year postpartum bet ween the t wo arms using logistic regression analyses and evaluat e, how glucose and insulin and other adipokine concentrations at baseline and at 6-8 weeks postpart um can predict glucose intoleranc e at 1 year postpartum.For the part ners, we will evaluate changes between groups and differenc es between groups at different time points (baseline at inclusion, 1 year postpartum) in weight and paternal eating behavior and mental health outcomes.
We will include pot ential covariates and test moderat ors of interest.Covariates: Analyses will be adjusted for maternal age, sex (for the children), baseline parameters, if applicable.Analyses will also be adjusted for BMI, EPDS depression score, pre-, peri-and early postnatal conditions/complications, socioeconomic status where applicable.Moderators: Where applicable, weight status and ethnicity as well as prediabetes status at the intial postpart um evaluation (6-8 weeks pp) and partners presence will be tested as possible moderators.Subgroup analyses will be performed according to weight status, mental health status (at risk vs not at risk patients), ethnicity, prediabetes status at the intial postpartum evaluation (6-8 weeks pp).
A process evaluation will also be performed (number of individual and workshop visits and coach contact, presence of partner).
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)

Data management
All study data will be entered by res earch staff (P h.D. students and study co-ordinators).All data will be precoded and stored in a secured dat abas e (Secutrial), which will be regularly updated by the CHUV IT Service.Double dat a entry will be done for the primary outcomes.For the rest of the data, a random 5% will be doublechecked.

Data Management System
We will use Secutrial, for which the PIs will carry res ponsibility.We are already using this system in the GDM Service after having tested and piloted it.A new database will be created for the purpose of this study.

Data security, access and back-up
Only the PIs and Co-P Is will have access to the secure dat abase, which is automatically backed up by the CHUV IT Service.

Analysis and archiving
For analysis by the trial statistician, data will be extracted and imported into a STA TA database.All study data will be archived for a minimum of 10 years after study termination or premature termination of the clinical trial.Paper documents will be stored at the Department of Endocrinology, Diabet es and Metabolism, and in the Department of Pediatric Cardiology

Electronic and central data validation
Not applicable.

Monitoring
Monitoring will be organized by the PI's and performed as follows: Initial visit (before the start of recruitment) -check that all members of the clinical and research team understand their roles and have received the appropriate training -check that all study procedures (as documented by SOPs) are put into place -check that all study documents (CRF) are prepared

Intermediate visit (after recruitment of 20 patients (10% of study population))
-check that all study procedures are followed according to SOPs and protocol -check the study documents (CRF, signed consent form) and their storage in a safe place -check the randomisation procedure and participant confidentiality The source data/documents will be accessible to monitors and questions are answered during monitoring.

Audits and Inspections
All study documentation and the source data/documents will be accessible to auditors/inspectors of the CEC and questions will be answered during inspections.All involved parties will ensure that the participant's data are kept strictly confidential.

Confidentiality, Data Protection
Direct access to source documents will be permitted for purposes of audits and inspections (12.4)Only the PI's and Co-PI's will have access to protocol, dataset, statistical code, etc during and after the study (publication, dissemination).12.6.Storage of biological material and related health data Blood samples will be collected from the participants and their offspring.The informed consent they will sign contains a specific paragraph, detailed in the information letter, explaining t he kind and purpose of storage of biological samples.
The coded blood samples will be stored for 10 years in a biobank, named MyS weet Heart Biobank , which will be held and maintained within the biobank of the Department of Endocrinology, Diabetes and Metabolism.This biobank has been registered by the CER-VD, and the B IL.The management of MyS weet Heart biobank will belong to PI's of the study, who will respect standard regulation and requirements for biobank management.The biobank management software S LIMS, used by the E DM biobank management, will be developed specifically and used for this study.
All health data related to the biobank will be held in the Secut rial database.The coding file allowing the identification of the participants, stays under the res ponsibility of the study PI's, and will not be available to anyone except for inspection purposes if required.

)
MySweetHeart Trial: Treatment-as-usual B) MySweetHeart Cohort: Not applicable their offspring in total; A) MySweetHeart Trial: 100 women with GDM and their offs pring in the control group; 100 women with GDM and their offspring in the intervention group.B) MySweetHeart Cohort: 100 women with GDM and their offspring; 100 women without GDM and their offspring.The 100 women with GDM in the control group of MyS weetHeart Trial and the 100 women with GDM of MySweetHeart Cohort are the same women.of First-Participant-In (planned) 06.2020 of Last-Participant-Out (planned) to diagnose GDM.

Figure 1 :
Figure 1: Modifiable risk factors of GDM that will be targeted by the multidimensional interdisciplinary lifestyle intervention

Figure
Figure2: Hy pothetical and highly -simplif ied causal relationships between gestational diabetes mellitus (GDM) and cardio-metabolic disorders.Two pathway s can be hy pothesized: 1) a direct effect of GDM on offspring's cardio-metabolic disorders; 2) an indirect eff ect through the mediator large f or gestational age (LGA).It means that if LGA was prev ented, part of the eff ect of GDM on cardio-metabolic disord ers wo uld be p rev ented.Sev eral conf ounding f actors (such as

-
timing: 1h -1h30 postprandial.Sedentary behaviour: Break sedentary time with physical activity every hour.Physical activity: Provide usual recommendations of 30 min per day of moderate physical activity (Endocrine Society) MENTAL HEALTH Depression: Screening and treatment of moderate depressive symptoms: Edinburgh Postnatal Depression Scale (EPDS) at first antenatal visit, 6-8 weeks postpartum and 1 year postpartum.

:
Screening and referral for moderate to severe depressive symptoms: Edinburgh Postnatal Depression Scale (EPDS) at first antenatal visit and 1 year postpartum.If EPDS = 13+, referral to Psychiatry Liaison Service.. Ensure that all adequate perinatal support services have been proposed Peers: Offer support by group sessions to initiate exchange and contact Partner: Integrate the partner in the consultations, groups sessions and the personal established goals No specific intervention BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) be (B.1) the cardiovascular structure and function during the fet al period; (B.2) neonatal adverse cardiovascular risk factors (notably blood cord total cholesterol, glycemia, insulin, c -peptide, hs-CRP).

STUDY SCHEDULETable 1 :
Schedule of events

Table 2 :
Schedule of assessments.All these variables are measured among women (and their offspring) wit h GDM.Variables also measured among women (and their offspring) without GDM of MySweetHeart Cohort are indicated by a star (*).

32 GW 30-34 GW 33-38 GW Birth 2-7 d PP 6-8 wks PP 1 yr PP MOTHER Physical exam
The primary outcomes are differences between the intervention and the control group in 1) the decrease in maternal weight between inclusion after GDM diagnosis and maternal weight at 1 yr postpartum and 2) the decrease in maternal symptoms of the Edinburgh Postnatal Depression score (EPDS) during the same time period.
A5.2.Secondary OutcomesDifferences between the intervention and the control group in other mat ernal secondary outcomes, such as (1) lifestyle behaviours, aerobic fitness and strength, body composition and cardio-metabolic laboratory biomarkers and (2) other mental health indicators during the peri -and postpartum period and offspring secon dary outcomes, such as (1) cardio-metabolic laboratory biomarkers at birth, body composition at birth and at 1 yr of age; and (2) mental health indicators at 1 yr of age.A5.3.Other Outcomes of InterestNot applicable.
Exclusion criteria: Women on strict bed-rest, with pre-existing diabetes or known severe mental disorder Population: 200 pregnant women with GDM, their partners, and their offspring.Study duration: 4 years Duration of patient's participation: 15 months

8.1. Identity of Investigational Products (treatment / medical device)
Drugs will only be administered for clinical care.No drugs will be administered to the participants within the framework of this study (see 8.2. for description of the multidimensional interdisciplinary intervention and treatment-as-usual condition).8

.1.1. Experimental Intervention (treatment / medical device) Not applicable. 8.1.2. Control Intervention (standard/routine/comparator treatment / medical device) Not applicable. 8.1.3. Packaging, Labelling and Supply (re -supply)
place during pregnancy and during the first year postpartum (see Table take

13. PUBLICATION AND DISSEMINATION POLICY
Unrestricted educational grants from Gottfried und Julia Bangert er-Rhy ner-Stiftung, Drey fus Foundation, and Swiss Diabetes Foundation.After having obtained some pilot data, a request will be submitted to the Swiss National Foundation to obtain additional funding.This study is categorized as « Other clinical study » according to art.61 OClin Category A. Therefore, no insurance is required.BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ BMJ