Towards Prepared mums (TOP-mums) for a healthy start, a lifestyle intervention for women with overweight and a child wish: study protocol for a randomised controlled trial in the Netherlands

Yvon E G Timmermans, Kim D G van de Kant, Dorien Reijnders, Lina M P Kleijkers, Edward Dompeling, Boris W Kramer, Luc J I Zimmermann, Régine P M Steegers-Theunissen, Marc E A Spaanderman, Anita C E Vreugdenhil, Yvon E G Timmermans, Kim D G van de Kant, Dorien Reijnders, Lina M P Kleijkers, Edward Dompeling, Boris W Kramer, Luc J I Zimmermann, Régine P M Steegers-Theunissen, Marc E A Spaanderman, Anita C E Vreugdenhil

Abstract

Introduction: Periconception obesity is associated with a higher risk for adverse perinatal outcomes such as gestational diabetes mellitus, preeclampsia, large for gestational age, operative delivery and preterm birth. Lifestyle interventions during pregnancy have resulted in insufficient effects on reducing these perinatal complications. A few reasons for this disappointing effect can be suggested: (1) the time period during pregnancy for improvement of developmental circumstances is too short; (2) the periconception period in which complications originate is not included; and (3) lifestyle interventions may not have been sufficiently multidisciplinary and customised. A preconception lifestyle intervention might be more effective to reduce perinatal complications. Therefore, the aim of the Towards Prepared mums study is to evaluate the effect of a lifestyle intervention starting prior to conception on lifestyle behaviour change.

Methods and analysis: This protocol outlines a non-blinded, randomised controlled trial. One hundred and twelve women (18-40 years of age) with overweight or obesity (body mass index≥25.0 kg/m2) who plan to conceive within 1 year will be randomised to either the intervention or care as usual group. The intervention group will receive a multidisciplinary, customised lifestyle intervention stimulating physical activity, a healthy diet and smoking cessation, if applicable. The lifestyle intervention and monitoring will take place until 12 months postpartum. The primary outcome is difference in weight in kg from baseline to 6 weeks postpartum. Secondary outcomes are gestational weight gain, postpartum weight retention, smoking cessation, dietary and physical activity habits. Furthermore, exploratory outcomes include body composition, cardiometabolic alterations, time to pregnancy, need for assisted reproductive technologies, perinatal complications of mother and child, and lung function of the child. Vaginal and oral swabs, samples of faeces, breast milk, placenta and cord blood will be stored for evaluation of microbial flora, epigenetic markers and breast milk composition. Furthermore, a cost-effectiveness analysis will take place.

Ethics and dissemination: Ethical approval was obtained from the Medical Ethical Committee of Maastricht University Medical Centre+ (NL52452.068.15/METC152026). Knowledge derived from this study will be made available by publications in international peer-reviewed scientific journals and will be presented at (inter)national scientific conferences. A dissemination plan for regional and national implementation of the intervention is developed.

Trial registration number: ClinicalTrials.gov NCT02703753.

Keywords: fetal medicine; maternal medicine; perinatology; preventive medicine.

Conflict of interest statement

Competing interests: RPMS-T is initiator and developer of Smarter Pregnancy and does not have a commercial interest. The Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre in Rotterdam is owner of this mHealth coaching tool.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
This vicious circle illustrates the intergenerational transmission of disease. The Towards Prepared mums (TOP-mums) study focuses on lifestyle improvement and the effects of this lifestyle improvement in the period between preconception and 1 year postpartum as illustrated in the upper part of the circle. The effects of an unhealthy lifestyle in this period can impact health of the entire life span: (a) longer time to conception and a higher risk for miscarriage; (b) higher risk for pregnancy complications such as gestational diabetes mellitus, gestational hypertension and preeclampsia; (c) unfavourable fetal programming by epigenetic processes modulating gene transcription, and by transmission of an unfavourable composition of microbial flora from mother to child; (d) higher risk for birth and neonatal complications such as operative delivery, small and large for gestational age, preterm birth and admission to the neonatal intensive care unit; (e) higher risk for developing obesity and pulmonary diseases such as wheezing and asthmatic disease; (f) higher risk for chronic diseases such as diabetes mellitus type 2, cardiovascular diseases and dyslipidaemia; (g) higher premature mortality rate.
Figure 2
Figure 2
Flow chart of study procedures.

References

    1. Murray CJL, Vos T, Lozano R, et al. . Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2197–223. 10.1016/S0140-6736(12)61689-4
    1. Godfrey KM, Barker DJP. Fetal programming and adult health. Public Health Nutr 2001;4:611–24. 10.1079/PHN2001145
    1. Godfrey KM, Reynolds RM, Prescott SL, et al. . Influence of maternal obesity on the long-term health of offspring. Lancet Diabetes Endocrinol 2017;5:53–64. 10.1016/S2213-8587(16)30107-3
    1. Steegers-Theunissen RPM, Twigt J, Pestinger V, et al. . The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update 2013;19:640–55. 10.1093/humupd/dmt041
    1. Gluckman PD, Hanson MA, Cooper C, et al. . Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 2008;359:61–73. 10.1056/NEJMra0708473
    1. Brewer CJ, Balen AH. The adverse effects of obesity on conception and implantation. Reproduction 2010;140:347–64. 10.1530/REP-09-0568
    1. Hassan MAM, Killick SR. Negative lifestyle is associated with a significant reduction in fecundity. Fertil Steril 2004;81:384–92. 10.1016/j.fertnstert.2003.06.027
    1. Homan GF, Davies M, Norman R. The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review. Hum Reprod Update 2007;13:209–23. 10.1093/humupd/dml056
    1. Lashen H, Fear K, Sturdee DW. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study. Hum Reprod 2004;19:1644–6. 10.1093/humrep/deh277
    1. Scholtens S, Wijga AH, Brunekreef B, et al. . Maternal overweight before pregnancy and asthma in offspring followed for 8 years. Int J Obes 2010;34:606–13. 10.1038/ijo.2009.194
    1. Gilliland FD, LI YU-FEN, Peters JM. Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med 2001;163:429–36. 10.1164/ajrccm.163.2.2006009
    1. Di Angelantonio E, Bhupathiraju S, Wormser D, et al. . Body-Mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 2016;388:776–86. 10.1016/S0140-6736(16)30175-1
    1. Scott-Pillai R, Spence D, Cardwell CR, et al. . The impact of body mass index on maternal and neonatal outcomes: a retrospective study in a UK obstetric population, 2004-2011. BJOG 2013;120:932–9. 10.1111/1471-0528.12193
    1. Voerman E, Santos S, Inskip H, et al. . Association of gestational weight gain with adverse maternal and infant outcomes. JAMA 2019;321:1702–15. 10.1001/jama.2019.3820
    1. Liu P, Xu L, Wang Y, et al. . Association between perinatal outcomes and maternal pre-pregnancy body mass index. Obes Rev 2016;17:1091–102. 10.1111/obr.12455
    1. Stothard KJ, Tennant PWG, Bell R, et al. . Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA 2009;301:636–50. 10.1001/jama.2009.113
    1. Ramachenderan J, Bradford J, McLean M. Maternal obesity and pregnancy complications: a review. Aust N Z J Obstet Gynaecol 2008;48:228–35. 10.1111/j.1479-828X.2008.00860.x
    1. Hyland A, Piazza K, Hovey KM, et al. . Associations between lifetime tobacco exposure with infertility and age at natural menopause: the women's health Initiative observational study. Tob Control 2016;25:706–14. 10.1136/tobaccocontrol-2015-052510
    1. Ko T-J, Tsai L-Y, Chu L-C, et al. . Parental smoking during pregnancy and its association with low birth weight, small for gestational age, and preterm birth offspring: a birth cohort study. Pediatr Neonatol 2014;55:20–7. 10.1016/j.pedneo.2013.05.005
    1. Eriksson JG, Sandboge S, Salonen MK, et al. . Long-Term consequences of maternal overweight in pregnancy on offspring later health: findings from the Helsinki birth cohort study. Ann Med 2014;46:434–8. 10.3109/07853890.2014.919728
    1. Burdge GC, Slater-Jefferies J, Torrens C, et al. . Dietary protein restriction of pregnant rats in the F 0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 2007;97:435–9. 10.1017/S0007114507352392
    1. Gohir W, Ratcliffe EM, Sloboda DM. Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk. Pediatr Res 2015;77:196–204. 10.1038/pr.2014.169
    1. Nieuwdorp M, Gilijamse PW, Pai N, et al. . Role of the microbiome in energy regulation and metabolism. Gastroenterology 2014;146:1525–33. 10.1053/j.gastro.2014.02.008
    1. Bäckhed F, Roswall J, Peng Y, et al. . Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015;17:690–703. 10.1016/j.chom.2015.04.004
    1. i-WIP Collaborative Group Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials. BMJ 2017;358.
    1. Getahun D, Ananth CV, Peltier MR, et al. . Changes in prepregnancy body mass index between the first and second pregnancies and risk of large-for-gestational-age birth. Am J Obstet Gynecol 2007;196:530.e1–8. 10.1016/j.ajog.2006.12.036
    1. Whiteman VE, Aliyu MH, August EM, et al. . Changes in prepregnancy body mass index between pregnancies and risk of gestational and type 2 diabetes. Arch Gynecol Obstet 2011;284:235–40. 10.1007/s00404-011-1917-7
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, et al. . Spirit 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 2013;346:e7586 10.1136/bmj.e7586
    1. American Psychiatric Association Diagnostic and statistical manual of mental disorders. 5th ed Washington, DC, 2013.
    1. Statistics Netherlands StatLine: birth, key numbers fertility, maternal age, region. Available: [Accessed 25 Jun 2019].
    1. Mutsaerts MAQ, van Oers AM, Groen H, et al. . Randomized trial of a lifestyle program in obese infertile women. N Engl J Med 2016;374:1942–53. 10.1056/NEJMoa1505297
    1. Knowler WC, Fowler SE. 10-Year follow-up of diabetes incidence and weight loss in the diabetes prevention program outcomes study. Lancet 2009;374:1677–86.
    1. Thangaratinam S, Rogozinska E, Jolly K, et al. . Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012;344:e2088 10.1136/bmj.e2088
    1. Vinter CA, Jensen DM, Ovesen P, et al. . The lip (lifestyle in pregnancy) study: a randomized controlled trial of lifestyle intervention in 360 obese pregnant women. Diabetes Care 2011;34:2502–7. 10.2337/dc11-1150
    1. Althuizen E, van der Wijden CL, van Mechelen W, et al. . The effect of a counselling intervention on weight changes during and after pregnancy: a randomised trial. BJOG 2013;120:92–9. 10.1111/1471-0528.12014
    1. Hoeger KM, Kochman L, Wixom N, et al. . A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril 2004;82:421–9. 10.1016/j.fertnstert.2004.02.104
    1. Foster GD, Wyatt HR, Hill JO, et al. . A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003;348:2082–90. 10.1056/NEJMoa022207
    1. Simpson JL. Incidence and timing of pregnancy losses: relevance to evaluating safety of early prenatal diagnosis. Am J Med Genet 1990;35:165–73. 10.1002/ajmg.1320350205
    1. Zhou H, Liu Y, Liu L, et al. . Maternal pre-pregnancy risk factors for miscarriage from a prevention perspective: a cohort study in China. Eur J Obstet Gynecol Reprod Biol 2016;206:57–63. 10.1016/j.ejogrb.2016.07.514
    1. Ramlau-Hansen CH, Thulstrup AM, Nohr EA, et al. . Subfecundity in overweight and obese couples. Hum Reprod 2007;22:1634–7. 10.1093/humrep/dem035
    1. Hull MG, North K, Taylor H, et al. . Delayed conception and active and passive smoking. The Avon longitudinal study of pregnancy and childhood study Team. Fertil Steril 2000;74:725–33.
    1. Nederlandse Vereniging voor Obstetrie en Gynaecologie Landelijke netwerkrichtlijn Subfertiliteit, 2010. Available:
    1. Burke BL, Arkowitz H, Menchola M. The efficacy of motivational interviewing: a meta-analysis of controlled clinical trials. J Consult Clin Psychol 2003;71:843–61. 10.1037/0022-006X.71.5.843
    1. Miller WR, Rollnick S. Motivational interviewing, second edition: preparing people for change. Guilford Publications, 2002.
    1. Van Dijk MR, Huijgen NA, Willemsen SP, et al. . Impact of an mHealth platform for pregnancy on nutrition and lifestyle of the reproductive population: a survey. JMIR mHealth uHealth 2016;4:e53 10.2196/mhealth.5197
    1. Van Dijk MR, Koster MPH, Rosman AN, et al. . Opportunities of mHealth in preconception care: preferences and experiences of patients and health care providers and other involved professionals. JMIR Mhealth Uhealth 2017;5:e123 10.2196/mhealth.7834
    1. van Dijk MR, Koster MPH, Willemsen SP, et al. . Healthy preconception nutrition and lifestyle using personalized mobile health coaching is associated with enhanced pregnancy chance. Reprod Biomed Online 2017;35:453–60. 10.1016/j.rbmo.2017.06.014
    1. van Dijk MR, Oostingh EC, Koster MPH, et al. . The use of the mHealth program smarter pregnancy in preconception care: rationale, study design and data collection of a randomized controlled trial. BMC Pregnancy Childbirth 2017;17:46 10.1186/s12884-017-1228-5
    1. Available:
    1. The Netherlands Nutrition Centre De Schijf van Vijf. Available: [Accessed 18 Jul 2018].
    1. Institute of Medicine Weight gain during pregnancy: reexamining the guidelines. Washington (DC): National Academies Press (US), 2009.
    1. Shiri R, Coggon D, Falah-Hassani K. Exercise for the prevention of low back and pelvic girdle pain in pregnancy: a meta-analysis of randomized controlled trials. European Journal of Pain 2018;22:19–27. 10.1002/ejp.1096
    1. Westerterp KR, Wouters L, van Marken Lichtenbelt WD. The Maastricht protocol for the measurement of body composition and energy expenditure with labeled water. Obes Res 1995;3:49–57. 10.1002/j.1550-8528.1995.tb00007.x
    1. Catalano PM, Wong WW, Drago NM, et al. . Estimating body composition in late gestation: a new hydration constant for body density and total body water. Am J Physiol Endocrinol Metab 1995;268:E153–8. 10.1152/ajpendo.1995.268.1.E153
    1. van Raaij JM, Peek ME, Vermaat-Miedema SH, et al. . New equations for estimating body fat mass in pregnancy from body density or total body water. Am J Clin Nutr 1988;48:24–9. 10.1093/ajcn/48.1.24
    1. Baecke JA, Burema J, Frijters JER. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 1982;36:936–42. 10.1093/ajcn/36.5.936
    1. Stunkard AJ, Messick S. The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res 1985;29:71–83. 10.1016/0022-3999(85)90010-8
    1. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998;351:805–6. 10.1016/S0140-6736(05)78933-9
    1. Matthews DR, Hosker JP, Rudenski AS, et al. . Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9. 10.1007/BF00280883
    1. Ben-Shlomo Y, Spears M, Boustred C, et al. . Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol 2014;63:636–46.
    1. Ding J, Wai KL, McGeechan K, et al. . Retinal vascular caliber and the development of hypertension: a meta-analysis of individual participant data. J Hypertens 2014;32:207–15.
    1. Nederlandse Vereniging voor Obstetrie en Gynaecologie Richtlijn diabetes mellitus en zwangerschap, 2018. Available:
    1. World Health Organization Definition, diagnosis and classification of diabetes mellitus and its complications : report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus, 1999. Available:
    1. Nederlandse Vereniging voor Obstetrie en Gynaecologie Richtlijn Hypertensieve aandoeningen in de zwangerschap, 2011. Available:
    1. Nederlandse Vereniging voor Obstetrie en Gynaecologie Richtlijn Foetale groeirestrictie, 2018. Available:
    1. Visser GHA, Eilers PHC, Elferink-Stinkens PM, et al. . New Dutch reference curves for birthweight by gestational age. Early Hum Dev 2009;85:737–44. 10.1016/j.earlhumdev.2009.09.008
    1. Stocks J, Sly PD, Tepper RS, et al. . Infant respiratory function testing. New York: Wiley-Liss, 1996.
    1. Galley JD, Bailey M, Kamp Dush C, et al. . Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS One 2014;9:e113026 10.1371/journal.pone.0113026
    1. Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol 2010;26:5–11. 10.1097/MOG.0b013e328333d751
    1. Lundgren SN, Madan JC, Emond JA, et al. . Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner. Microbiome 2018;6 10.1186/s40168-018-0490-8
    1. Seganfredo FB, Blume CA, Moehlecke M, et al. . Weight-Loss interventions and gut microbiota changes in overweight and obese patients: a systematic review. Obes Rev 2017;18:832–51. 10.1111/obr.12541
    1. Kerr CA, Grice DM, Tran CD, et al. . Early life events influence whole-of-life metabolic health via gut microflora and gut permeability. Crit Rev Microbiol 2015;41:326–40. 10.3109/1040841X.2013.837863
    1. Koren O, Goodrich JK, Cullender TC, et al. . Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 2012;150:470–80. 10.1016/j.cell.2012.07.008
    1. Dominguez-Bello MG, Costello EK, Contreras M, et al. . Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 2010;107:11971–5. 10.1073/pnas.1002601107
    1. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, et al. . Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 2016;22:250–3. 10.1038/nm.4039
    1. Kon IY, Shilina NM, Gmoshinskaya MV, et al. . The study of breast milk IGF-1, leptin, ghrelin and adiponectin levels as possible reasons of high weight gain in breast-fed infants. Ann Nutr Metab 2014;65:317–23. 10.1159/000367998
    1. Sadr Dadres G, Whitaker KM, Haapala JL, et al. . Relationship of maternal weight status before, during, and after pregnancy with breast milk hormone concentrations. Obesity 2019;27:621–8. 10.1002/oby.22409
    1. Lipkie TE, Morrow AL, Jouni ZE, et al. . Longitudinal survey of carotenoids in human milk from urban cohorts in China, Mexico, and the USA. PLoS One 2015;10:e0127729 10.1371/journal.pone.0127729
    1. Nelissen ECM, Dumoulin JCM, Busato F, et al. . Altered gene expression in human placentas after IVF/ICSI. Hum Reprod 2014;29:2821–31. 10.1093/humrep/deu241
    1. Herdman M, Gudex C, Lloyd A, et al. . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36. 10.1007/s11136-011-9903-x
    1. Janssen MF, Pickard AS, Golicki D, et al. . Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study. Qual Life Res 2013;22:1717–27. 10.1007/s11136-012-0322-4
    1. Wilkinson MD, Dumontier M, Aalbersberg IJJ, et al. . The fair guiding principles for scientific data management and stewardship. Sci Data 2016;3 10.1038/sdata.2016.18
    1. Catalano P, deMouzon SH. Maternal obesity and metabolic risk to the offspring: why lifestyle interventions may have not achieved the desired outcomes. Int J Obes 2015;39:642–9. 10.1038/ijo.2015.15
    1. Temel S, van Voorst SF, Jack BW, et al. . Evidence-Based preconceptional lifestyle interventions. Epidemiol Rev 2014;36:19–30. 10.1093/epirev/mxt003
    1. Hillemeier MM, Downs DS, Feinberg ME, et al. . Improving women's preconceptional health: findings from a randomized trial of the strong healthy women intervention in the central Pennsylvania women's health study. Womens Health Issues 2008;18:S87–96. 10.1016/j.whi.2008.07.008
    1. Lan L, Harrison CL, Misso M, et al. . Systematic review and meta-analysis of the impact of preconception lifestyle interventions on fertility, obstetric, fetal, anthropometric and metabolic outcomes in men and women. Hum Reprod 2017;32:1925–40. 10.1093/humrep/dex241
    1. Mutsaerts MAQ, Kuchenbecker WKH, Mol BW, et al. . Dropout is a problem in lifestyle intervention programs for overweight and obese infertile women: a systematic review. Hum Reprod 2013;28:979–86. 10.1093/humrep/det026
    1. Burgess E, Hassmén P, Pumpa KL. Determinants of adherence to lifestyle intervention in adults with obesity: a systematic review. Clin Obes 2017;7:123–35. 10.1111/cob.12183
    1. Willeboordse M, van de Kant KDG, Tan FES, et al. . Correction: a multifactorial weight reduction programme for children with overweight and asthma: a randomized controlled trial. PLoS One 2016;12:e0181130 10.1371/journal.pone.0181130
    1. Hutchinson SG, van Breukelen G, van Schayck CP, et al. . Motivational interviewing and urine cotinine feedback to stop passive smoke exposure in children predisposed to asthma: a randomised controlled trial. Sci Rep 2017;7:15473 10.1038/s41598-017-15158-2
    1. Rijks JM, Plat J, Mensink RP, et al. . Children with morbid obesity benefit equally as children with overweight and obesity from an ongoing care program. J Clin Endocrinol Metab 2015;100:3572–80. 10.1210/jc.2015-1444

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