Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
Published online: October 2, 2014
Dietary and Lifestyle Advice for Pregnant Women Who Are Overweight or Obese: The LIMIT Randomized Trial Jodie M. Dodd School of Paediatrics and Reproductive Health, The University of Adelaide, and The Robinson Institute, Adelaide, S.A., and Department of Perinatal Medicine, Women’s and Babies’ Division, Women’s and Children’s Hospital, North Adelaide, S.A., Australia
Abstract Overweight and obesity during pregnancy are common and are associated with an increased risk of adverse health outcomes for both the mother and the infant. However, robust evidence about the effect of antenatal dietary and lifestyle interventions on health outcomes is lacking. We conducted a multicenter, randomized trial, recruiting 2,212 women (from 3 public maternity hospitals across South Australia) with a singleton pregnancy between 10+0 and 20+0 weeks’ gestation and a BMI ≥25. The women were randomized to lifestyle advice (n = 1,108) or standard care (n = 1,104). Women randomized to lifestyle advice participated in a comprehensive dietary and lifestyle intervention over the course of their pregnancy (delivered by research staff), while women randomized to standard care received pregnancy care according to local guidelines, which did not include such information. Provision of the lifestyle intervention was associated with a significant 18% relative risk reduction in the chance of infants being born with a birth weight above 4 kg. No other significant differences were identified in maternal pregnancy and birth outcomes between the two treatment groups.
© 2014 S. Karger AG, Basel 0250–6807/14/0644–0197$39.50/0 E-Mail [email protected] www.karger.com/anm
Observational studies highlight the association between a high infant birth weight and the subsequent risk of childhood and adulthood obesity. Antenatal interventions that are effective in reducing high infant birth weights therefore represent a significant strategy to tackle obesity from a population health perspective, while ongoing interrogation of the biospecimens and measurements, including ongoing childhood follow-up, will provide a unique opportunity to evaluate the mechanistic pathways of maternal-to-infant/ childhood obesity. © 2014 S. Karger AG, Basel
It is estimated that more than 110 million children [1] and 1.3 billion adults [2] globally are overweight (defined as a BMI between 25.0 and 29.9) or obese (defined as a BMI ≥30.0), representing a significant contribution to the worldwide burden of disease [3]. The main adverse consequences of adult obesity relate to increased risks of cardiovascular disease, type 2 diabetes, and several cancers, thereby significantly reducing the life expectancy [3] and contributing to a significant economic burden [4]. Estimates from the USA indicate that in 2006 USD 147 billion dollars were spent on obesity-related complications, representing 10% of the country’s total health care expenditure [5], with projections indicating that these Prof. Jodie M. Dodd The University of Adelaide, Women’s and Children’s Hospital 72 King William Road North Adelaide, SA 5006 (Australia) E-Mail jodie.dodd @ adelaide.edu.au
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
Key Words Pregnancy · Obesity · Intervention · Randomized controlled trial
198
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
The LIMIT randomized trial [22] recruited and randomized 2,212 women with a BMI ≥25 and a singleton pregnancy between 10+0 and 2+0 weeks’ gestation from the 3 major metropolitan maternity hospitals within Adelaide, S.A., Australia. All women presenting for antenatal care had their height and weight measured, and their BMI was calculated at the time of their first antenatal appointment. After providing written informed consent, the women were randomized using a central telephone randomization service. A computer-generated schedule was used, with balanced variable blocks and stratification for parity (0 vs. 1 or more), BMI at the antenatal booking (25–29.9 vs. ≥30), and collaborating center. Women randomized to the lifestyle advice group participated in a comprehensive dietary and lifestyle intervention over the course of their pregnancy, including a combination of dietary, exercise, and behavioral strategies, delivered by a research dietician and trained research assistants [23]. The dietary advice provided was consistent with current Australian dietary standards [24] in which women are encouraged to maintain a balance of carbohydrates, fat, and protein and reduce their intake of foods high in refined carbohydrates and saturated fats while increasing their intake of fiber, promoting the consumption of 2 servings of fruit, 5 servings of vegetables, and 3 servings of dairy each day [24]. Advice regarding exercise in pregnancy is primarily focused on encouraging women to increase their activity through walking and incidental activity [25]. After randomization, a detailed dietary and physical activity history was obtained from women during an initial planning session with a research dietician. Individualized information was provided, including meal plans, time-saving and easy-to-prepare healthy recipes, advice regarding simple food substitutions (e.g. reducing sugarsweetened soft drinks and fruit juices, reducing added sugar and foods high in refined carbohydrates, and lowfat alternatives), healthy snack and eating-out options, and general guidelines associated with healthy food preparation. At this session, each woman was encouraged to identify and set achievable goals for dietary and exercise changes. Furthermore, they were supported in making these lifestyle changes and self-monitoring their progress utilizing a provided booklet. Specifically, each woman was encouraged to identify potential barriers to them implementing their dietary goals, and using these perceived barriers they were assisted in solving the problem and developing individualized strategies to facilitate their successful implementation.
Dodd
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
costs will continue to double each decade, representing up to 18% of the total health care expenditure by 2030 [6]. The impact of maternal overweight and obesity during pregnancy and childbirth is substantial, with a large proportion of pregnant women being overweight or obese, and estimates have increased from 35% reported in 2006 [7] to more recent figures in the order of 50% or more [8–11]. There are well-documented risks of poor health outcomes associated with obesity during pregnancy, and the risks increase as the BMI increases [7, 9]. Recognized pregnancy complications include an increased risk of hypertension, preeclampsia, gestational diabetes, and the need for both induction of labor and a caesarean section [7, 9, 12]. Furthermore, there is increasing recognition of the health implications of maternal overweight and obesity for the infant. Infants born to women who are overweight or obese are more likely to require nursery admission and treatment for both hypoglycemia and jaundice [7, 9]. These infants are also more likely to have a birth weight above 4 kg [9, 12–14], which in turn has been recognized as a risk factor for subsequent obesity in both childhood and adulthood [15, 16]. Complicating the relationship between the maternal prepregnancy BMI and pregnancy outcomes is the independent effect of gestational weight gain (GWG), which is also associated with many of these same adverse pregnancy outcomes [7, 9, 17, 18]. There is a substantial amount of literature on maternal weight gain in pregnancy that has been summarized by the Institute of Medicine [19, 20]. Since 1970, most studies have reported average weight gains of 10–15 kg, with the rate of gain in the last half of pregnancy ranging from 0.45 to 0.52 kg/week, although this varies considerably among overweight and obese women, with many having GWG exceeding this average [19]. The original focus of the Institute of Medicine recommendations was the relationship between GWG and fetal growth restriction [19] in an era before the widespread prevalence of obesity. These recommendations have since been reviewed [20], recognizing the trade-off that often exists between maternal and infant outcomes [21] and advocating a GWG of 7.0–11.5 kg for women who are overweight and a GWG of 5.0–9.0 kg for women who are obese [20]. It is estimated that more than 60% of pregnant women report a weight gain in excess of the Institute of Medicine recommendations [20]. In view of the association between obesity and GWG, there has been intense research interest in the evaluation of interventions, particularly among women who are overweight or obese, to limit GWG.
assessment of the participants has been undertaken (and completed) at 6 and 18 months of age, with follow-up at age 3 years currently ongoing. The Pedersen hypothesis, also known as the developmental overnutrition hypothesis [30], was proposed as a possible explanation for the relationship observed between maternal diabetes in pregnancy and increased fetal adiposity or overgrowth. It was postulated that maternal hyperglycemia contributed to increased transplacental glucose transfer, with subsequent fetal hyperglycemia and increased insulin production. The overall net effect of fetal hyperinsulinemia was an increase in insulin-mediated fetal growth. Subsequently, the role of other fuel substrates, including free fatty acids, triglycerides, and amino acids, was also recognized [30]. In recent times, the fetal developmental overnutrition hypothesis has been expanded in recognition of the potentially significant metabolic impact of maternal obesity [31]. Furthermore, there is increasing evidence to support an effect of maternal obesity on direct alterations in the placental transfer of metabolic substrates. Both maternal overweight and obesity are risk factors for the subsequent development of gestational diabetes [7, 9, 32]. Metabolically, obesity and gestational diabetes share similar characteristics, including insulin resistance, hyperglycemia, hyperlipidemia, and a low-grade state of chronic inflammation, which in turn has been shown to alter the availability and the placental transfer of nutrients to the developing fetus [31]. Adipose tissue also has a critical role in innate immune sensing, with various adipocytokines (leptin, TNF-α, and IL-6) acting to antagonize the effects of insulin [33–38]. Through manipulation of the maternal diet during pregnancy and early postnatal feeding, animal studies have identified significant alterations in offspring body composition and adiposity, potentially mediated through modification of appetite and energy expenditure [39–41]. In rodents, diet-induced maternal obesity has been shown to cause obesity, diabetes, and fatty liver disease, as well as behavior and learning changes in offspring [42]. The effects of maternal dietary modification during pregnancy on infant body composition and metabolic health are less clear. Cohort studies have suggested, despite minimal changes in birth weight, that infants born to women who are overweight or obese have an increased percentage of body fat and fat mass compared to infants born to women with a normal BMI [43–45]. Similarly, infants born to women with gestational diabetes have been demonstrated to have an increased fat mass and a reduced lean tissue mass at birth, again despite minimal
The LIMIT Trial
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
199
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
This information was reinforced during subsequent inputs across pregnancy provided by the research dietician (at 28 weeks’ gestation) and trained research assistants (via telephone contact at 22, 24, and 32 weeks’ gestation and a face-to-face visit at 36 weeks’ gestation). Women who were randomized to receiving standard care continued their pregnancy care according to statewide perinatal practice and local hospital guidelines, which did not include routine provision of dietary or exercise advice or information regarding GWG targets [26]. Outcomes focused on a range of maternal and infant clinical outcomes, in addition to maternal dietary and physical activity changes, maternal psychological wellbeing and quality of life, ultrasound assessment of fetal growth and adiposity, and anthropometry (maternal, paternal, and neonatal). A total of 2,212 women were recruited and randomized to the LIMIT trial. The median BMI of the cohort was 31.1 (IQR 27.9–35.8), with 42.1% of women being overweight and 57.9% obese [22]. Infants born to women who received lifestyle advice were 18% less likely to have a high birth weight (p = 0.04) [22] compared to infants born to women who received standard care. No statistically significant differences were identified between the two groups with regard to maternal antenatal, labor, or birth outcomes [22]. In a post hoc analysis, the mean GWG of approximately 9.4 kg did not differ between the two treatment groups, with GWG above the Institute of Medicine recommendations for approximately 42% of all women [22]. Despite the lack of a difference in GWG between the two treatment groups, women who received lifestyle advice were successful in making significant changes to both their diet and their physical activity [Dodd et al., unpubl. data]. The findings of the LIMIT randomized trial [22] provide evidence that changes in maternal diet and physical activity during pregnancy can reduce the risk of high infant birth weight among women who are overweight or obese. This is of great significance given the observational data from the US Early Childhood Longitudinal Study [27], which highlights that children with a birth weight greater than 4 kg are at a significantly greater risk for obesity in adolescence. In that cohort, while the incidence of birth weight over 4 kg was 12%, 36% of individuals who were obese at age 14 years had a birth weight over 4 kg [27]. Therefore, any antenatal intervention that is successful in reducing the risk of high infant birth weight potentially represents a significant strategy to tackle obesity from a population health perspective [28, 29], with ongoing follow-up of participants from the LIMIT randomized trial into childhood being essential. To this end,
Table 1. Specimen/measurement and time point of collection
Type
Time point
Anthropometric measure
Biological specimen
Maternal
Trial entry and 36 weeks’ GA 28 weeks’ GA
Weight, height, BMI BC, and SFTM
Cardiometabolic responsea Buffy coat: genetic analysesb Cardiometabolic responsea
Weight, height, BMI BC, and SFTM
Saliva: genetic analysesb
Paternal Fetal
28 and 36 weeks’ GA
Ultrasound fetal growth and adiposity measures
Neonatal
Birth
Weight, length, BMI BC, SFTM, and BIA
Cord blood: cardiometabolic responsea Nucleated blood cells: genetic analysesb
Infant
6, 18, and 36 months
Weight, length/height, BMI BC, SFTM, and BIA
Saliva: genetic analysesb
differences in birth weight [46, 47]. Furthermore, there are reports indicating that these differences in the distribution of adipose tissue persist into early childhood [48, 49]. The maternal dietary fat intake during pregnancy also appears to impact childhood adiposity, with a diet high in polyunsaturated fatty acids being associated with reduced childhood adiposity as measured by skinfold thickness [50], in addition to predicting the fat mass as measured by DEXA scans in children aged 4 and 6 years [51]. Features of the metabolic syndrome, specifically abdominal adiposity, hypertension, and type 2 diabetes, are being increasingly linked to changes in the intrauterine environment and epigenetic modification of gene expression and subsequent changes in body composition in fetal life and early infancy, reflecting altered ratios of fat and lean tissue mass, as well as changes in metabolic pathway regulation [52]. The well-described features of the metabolic syndrome in adults have been documented increasingly in children [1, 53–55], with population studies indicating that 25% of 8-year-old and 29% of 14-yearold children have features of the syndrome [53]. The effect of maternal obesity and GWG on the risk of a subsequent cardiovascular risk and hypertension in offspring is also emerging, with both maternal prepregnancy obesity and high degrees of GWG documented to be associated with an altered cardiovascular risk profile and a higher blood pressure in children [15, 56]. While these 200
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
associations have not been universally reported [42, 57, 58], some suggest that the changes remain evident up until 21 years of age [59]. While observational studies have indicated an association between both a high maternal BMI and a high GWG and the subsequent risk of childhood obesity and cardiometabolic disease, the precise operational mechanisms that contribute to this are unclear. The recent consensus statement from the International Life Sciences Institute, Europe [60], relating to obesity in pregnancy recommended that: ‘assessment of relationships between maternal obesity and offspring health would be facilitated by … long-term follow-up without interruption throughout childhood and into adulthood, determination of parental, neonatal and childhood adiposity and fat distribution, … measurement of growth trajectories in the fetus, … collection of paternal, maternal, and child DNA, in addition to maternal and cord blood biomarkers’ [60]. As outlined in table 1, much of this extensive range of biospecimens and measurements has been prospectively collected within the context of the LIMIT randomized trial which, in combination with ongoing childhood assessment, will provide a unique and invaluable resource facilitating evaluation of the mechanistic pathways of maternal-toinfant/childhood obesity. Both a high maternal BMI [7, 9] and a high GWG [17, 18] have been recognized as significant and independent predictors of future child and adult obesity [61–64]. Dodd
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
GA = Gestational age; BC = body circumferences; BIA = bioimpedance analysis; SFTM = skin fold thickness measurement. a Includes carbohydrate metabolism, triglycerides, and adipocytokines. b Include both genetic and epigenetic evaluations.
While the association between maternal and infant and childhood adiposity is likely to reflect a combination of shared genetic and environmental factors in addition to in utero programming pathways, the latter may be modifiable and therefore of enormous significance as a strategy to prevent or limit the early onset of obesity. The clinical findings of the LIMIT randomized trial, and the subsequent detailed evaluation of mechanistic information, will continue to providing unique opportunities to evaluate the contribution of the intrauterine environment to the pathways between maternal and child obesity.
Acknowledgement This article reports an extended version of the presentation made at the conference ‘The Power of Programming 2014. International Conference on Developmental Origins of Adiposity and Long-Term Health’, held in Munich on March 13–15, 2014. To participate in the conference, the author received funding from the European Union’s 7th Framework Programme (FP7/2007–2013), EarlyNutrition project, under grant agreement No. 289346.
Disclosure Statement The author has no financial interests to disclose.
References
The LIMIT Trial
13 Cedergren MI: Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol 2004;103:219–224. 14 Cnattingius S, Bergstrom R, Lipworth L, Kramer MS: Prepregnancy weight and the risk of adverse pregnancy outcomes. N Engl J Med 1998;338:147–152. 15 Fraser A, Tilling K, Macdonald-Wallis C, Sattar N, Brion MJ, Benfield L, et al: Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation 2010; 121: 2557–2564. 16 Tikellis G, Ponsonby AL, Wells JC, Pezic A, Cochrane J, Dwyer T: Maternal and infant factors associated with neonatal adiposity: results from the Tasmanian Infant Health Survey. Int J Obes 2012;36:496–504. 17 Cedergren MI: Effects of gestational weight gain and body mass index on obstetric outcomes in Sweden. Int J Gynaecol Obst 2006; 93:269–274. 18 Cedergren MI: Optimal gestational weight gain for body mass index categories. Obstet Gynecol 2007;110:759–764. 19 Institute of Medicine: Nutrition during Pregnancy. Washington, National Academies Press, 1990. 20 Institute of Medicine: Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, National Academies Press, 2009. 21 Rasmussen KM, Abrams B, Bodnar LM, Butte NF, Catalano PM, Siega-Riz AM: Recommendations for weight gain during pregnancy in the context of the obesity epidemic. Obstet Gynecol 2010;116:1191–1195. 22 Dodd JM, Turnbull DA, McPhee AJ, Deussen AR, Grivell RM, Yelland LN, et al: Antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial. BMJ 2014;348:g1285. 23 Dodd JM, Turnbull DA, McPhee AJ, Wittert G, Crowther CA, Robinson JS: Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial. BMC Pregnancy Childbirth 2011;11:79.
24 Australian Guide to Healthy Eating. http:// www.health.gov.au/internet/main/publishing.nsf/content/health-pubhlth-publicatdocument-fdcons-cnt.htm. 25 Royal College of Obstetricians and Gynaecologists: Recreational exercise and pregnancy: information for you. London, RCOG Press, 2006. 26 South Australian Perinatal Guidelines: normal pregnancy, labour and puerperium. 2007. http://www.health.sa.gov.au/ppg/Default. aspx?PageContentID=2248&tabid = 54%5D. 27 Cunningham SA, Kramer MR, Narayan KM: Incidence of childhood obesity in the United States. N Engl J Med 2014;370:403–411. 28 Catalano PM: Obesity and pregnancy – the propagation of a viscous cycle? J Clin Endocrinol Metab 2003;88:3505–3506. 29 Poston L: Healthy eating in pregnancy – always a good idea, now with more supporting evidence. BMJ 2014;348:g1739. 30 Pedersen J: Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica 1954;16:330–342. 31 Catalano PM, Hauguel-De Mouzon S: Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am J Obstet Gynecol 2011;204:479–487. 32 Athukorala C, Crowther CA, Willson K: Women with gestational diabetes mellitus in the ACHOIS trial: risk factors for shoulder dystocia. Aust NZ J Obstet Gynaecol 2007;47: 37–41. 33 Sjoholm A, Nystrom T: Endothelial inflammation in insulin resistance. Lancet 2005;365: 610–613. 34 Han TS, Sattar N, Williams K, GonzalezVillalpando C, Lean ME, Haffner SM: Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 2002;25:2016–2021. 35 Duncan BB, Schmidt MI, Pankow JS, et al: Low-grade systemic inflammation and the development of type 2 diabetes. Diabetes 2003;52:1799–1805.
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
201
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
1 Cali AM, Caprio S: Obesity in children and adolescents. J Clin Endocrinol Metab 2008; 93:S31–S36. 2 World Health Organization: WHO obesity and overweight fact sheet (No 311). 2006 http://www.who.int/mediacentre/factsheets/ fs311/en/print.html. 3 Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ; Comparative Risk Assessment Collaborating Group: Selected major risk factors and global and regional burden of disease. Lancet 2002;360:1347–1360. 4 Access Economics: The Growing Cost of Obesity in 2008: Three Years On. Canberra, Diabetes Australia, 2008. 5 Roehr B: ‘Soda tax’ could help tackle obesity, says US director of public health. BMJ 2009; 339:b3176. 6 Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK: Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity 2008;16:2323–2330. 7 Callaway LK, Prins JB, Chang AM, McIntyre HD: The prevalence and impact of overweight and obesity in an Australian obstetric population. Med J Aust 2006;184:56–59. 8 Scheil W, Scott J, Catcheside B, Sage L: Pregnancy Outcome in South Australia 2010. Adelaide, SA Health 2012. 9 Dodd JM, Grivell RM, Nguyen A-M, Chan A, Robinson JS: Maternal and perinatal health outcomes by body mass index category. Aust NZ J Obstet Gynaecol 2011;51:136–140. 10 Chu SY, Kim SY, Bish CL: Prepregnancy obesity prevalence in the United States, 2004– 2005. Matern Child Health J 2009;13:614–620. 11 NICE issues pregnancy weight management guidance, as the number of obese mothers soars. 2010. http://www.nice.org.uk/newsroom/news/NICEissuesPregnancyWeightManagementGuideance. 12 Abenhaim HA, Kinch RA, Morin L, Benjamin A, Usher R: Effect of prepregnancy body mass index categories on obstetrical and neonatal outcomes. Arch Gynecol Obstet 2007; 275: 39–43.
202
47 Catalano PM, Kirwan JP, Haugel-de Mouzon S, King J: Gestational diabetes and insulin resistance: role in short and long-term implications for mother and fetus. J Nutr 2003; 133: 1674S–1683S. 48 Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators: Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003– 2015. 49 Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM: Metformin in gestational diabetes: the offspring follow-up (MiG TOFU) – body composition at 2 years of age. Diabetes Care 2011;34:2279–2284. 50 Donahue SM, Rifas-Shiman SL, Gold DR, Jouni ZE, Gillman MW, Oken E: Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort. Am J Clin Nutr 2011;93:780–788. 51 Moon RJ, Harvey NC, Robinson SM, Ntani G, Davies JH, Inskip HM, et al: Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. J Clin Endocrinol Metab 2013;98:299–307. 52 James WP: The epidemiology of obesity: the size of the problem. J Intern Med 2008; 263: 336–352. 53 Beillin L, Huang RC: Childhood obesity, hypertension, the metabolic syndrome and adult cardiovascular disease. Clin Exp Pharmacol Physiol 2008;35:409–411. 54 Bokor S, Frelut ML, Vania A, Hadjiathanasiou CG, Anastassakou M, Malecka-Tendera E, et al: Prevalence of metabolic syndrome in European obese children. Int J Pediatr Obes 2008;3:3–8. 55 Seki M, Matsuo T, Caria Carrilho AJ: Prevalence of metabolic syndrome and associated risk factors in Brazilian school children. Public Health Nutr 2009;12:947–952. 56 Oken E, Taveras EM, Kleinman KP, Rich-Edwards JW, Gillman MW: Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol 2007;196:322–328.
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
57 Godfrey KM, Forrester T, Barker DJ, Jackson AA, Landman JP, Hall JS, et al: Maternal nutritional status in pregnancy and blood pressure in childhood. Br J Obstet Gynaecol 1994; 101:398–403. 58 Clark PM, Atton C, Law CM, Shiell A, Godfrey K, Barker DJ: Weight gain in pregnancy, triceps skinfold thickness, and blood pressure in offspring. Obstet Gynecol 1998; 91: 103– 107. 59 Mamun AA, Kinarivala M, O’Callaghan MJ, Williams GM, Najman JM, Callaway LK: Associations of excess weight gain during pregnancy with long-term maternal overweight and obesity: evidence from 21 y postpartum follow-up. Am J Clin Nutr 2010; 91: 1336– 1341. 60 Poston L, Harthoorn LF, Van Der Beek EM; Contributirs to the ILSI Europe Workshop: Obesity in pregnancy: implications for the mother and lifelong health of the child – a consensus statement. Pediatr Res 2011; 69: 175–180. 61 Godfrey KM, Inskip HM, Hanson MA: The long-term effects of prenatal development on growth and metabolism. Semin Reprod Med 2011;29:257–265. 62 Wells JC, Haroun D, Levene D, Darch T, Williams JE, Fewtrell MS: Prenatal and postnatal programming of body composition in obese children and adolescents: evidence from anthropometry, DXA and the 4-component model. Int J Obes 2011;35:534–540. 63 Winter JD, Langenberg P, Krugman SD: Newborn adiposity by body mass index predicts childhood overweight. Clin Pediatr 2010;49:866–870. 64 Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C: Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 2005;331:929.
Dodd
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
36 Lyon CJ, Law RE, Hsueh WA: Minireview: adiposity, inflammation and atherogenesis. Endocrinology 2003;144:2195–2200. 37 Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM: C-reactive protein, interleukin-6 and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327–334. 38 Greenberg AS, Obin MS: Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:461–465. 39 Robinson SM, Godfrey KM: Feeding practices in pregnancy and infancy: relationship with the development of overweight and obesity in childhood. Int J Obes 2008;32:S4–S10. 40 Simmons R: Perinatal programming of obesity. Semin Perinatol 2008;32:371–374. 41 Gluckman PD, Hanson MA, Cooper C, Thornburg KL: Effect of in utero and earlylife conditions on adult health and disease. N Engl J Med 2008;359:61–73. 42 Laor A, Stevenson DK, Shemer J, Gale R, Seidman DS: Size at birth, maternal nutritional status in pregnancy, and blood pressure at age 17: population based analysis. BMJ 1997;315: 449–453. 43 Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al: Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010;91:1745–1751. 44 Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA: Impact of maternal body mass index on neonate birth weight and body composition. Am J Obstet Gynecol 2008;198: 416.e1–416.e6. 45 Sewell MF, Huston-Presley L, Super DM, Catalano PM: Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006;195:1100– 1103. 46 Durnwald CP, Ehrenberg HM, Mercer BM: The impact of maternal obesity and weight gain in vaginal birth after caesarean section success. Am J Obstet Gynecol 2004; 191: 954– 957.
Published online: October 2, 2014
Dietary and Lifestyle Advice for Pregnant Women Who Are Overweight or Obese: The LIMIT Randomized Trial Jodie M. Dodd School of Paediatrics and Reproductive Health, The University of Adelaide, and The Robinson Institute, Adelaide, S.A., and Department of Perinatal Medicine, Women’s and Babies’ Division, Women’s and Children’s Hospital, North Adelaide, S.A., Australia
Abstract Overweight and obesity during pregnancy are common and are associated with an increased risk of adverse health outcomes for both the mother and the infant. However, robust evidence about the effect of antenatal dietary and lifestyle interventions on health outcomes is lacking. We conducted a multicenter, randomized trial, recruiting 2,212 women (from 3 public maternity hospitals across South Australia) with a singleton pregnancy between 10+0 and 20+0 weeks’ gestation and a BMI ≥25. The women were randomized to lifestyle advice (n = 1,108) or standard care (n = 1,104). Women randomized to lifestyle advice participated in a comprehensive dietary and lifestyle intervention over the course of their pregnancy (delivered by research staff), while women randomized to standard care received pregnancy care according to local guidelines, which did not include such information. Provision of the lifestyle intervention was associated with a significant 18% relative risk reduction in the chance of infants being born with a birth weight above 4 kg. No other significant differences were identified in maternal pregnancy and birth outcomes between the two treatment groups.
© 2014 S. Karger AG, Basel 0250–6807/14/0644–0197$39.50/0 E-Mail [email protected] www.karger.com/anm
Observational studies highlight the association between a high infant birth weight and the subsequent risk of childhood and adulthood obesity. Antenatal interventions that are effective in reducing high infant birth weights therefore represent a significant strategy to tackle obesity from a population health perspective, while ongoing interrogation of the biospecimens and measurements, including ongoing childhood follow-up, will provide a unique opportunity to evaluate the mechanistic pathways of maternal-to-infant/ childhood obesity. © 2014 S. Karger AG, Basel
It is estimated that more than 110 million children [1] and 1.3 billion adults [2] globally are overweight (defined as a BMI between 25.0 and 29.9) or obese (defined as a BMI ≥30.0), representing a significant contribution to the worldwide burden of disease [3]. The main adverse consequences of adult obesity relate to increased risks of cardiovascular disease, type 2 diabetes, and several cancers, thereby significantly reducing the life expectancy [3] and contributing to a significant economic burden [4]. Estimates from the USA indicate that in 2006 USD 147 billion dollars were spent on obesity-related complications, representing 10% of the country’s total health care expenditure [5], with projections indicating that these Prof. Jodie M. Dodd The University of Adelaide, Women’s and Children’s Hospital 72 King William Road North Adelaide, SA 5006 (Australia) E-Mail jodie.dodd @ adelaide.edu.au
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
Key Words Pregnancy · Obesity · Intervention · Randomized controlled trial
198
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
The LIMIT randomized trial [22] recruited and randomized 2,212 women with a BMI ≥25 and a singleton pregnancy between 10+0 and 2+0 weeks’ gestation from the 3 major metropolitan maternity hospitals within Adelaide, S.A., Australia. All women presenting for antenatal care had their height and weight measured, and their BMI was calculated at the time of their first antenatal appointment. After providing written informed consent, the women were randomized using a central telephone randomization service. A computer-generated schedule was used, with balanced variable blocks and stratification for parity (0 vs. 1 or more), BMI at the antenatal booking (25–29.9 vs. ≥30), and collaborating center. Women randomized to the lifestyle advice group participated in a comprehensive dietary and lifestyle intervention over the course of their pregnancy, including a combination of dietary, exercise, and behavioral strategies, delivered by a research dietician and trained research assistants [23]. The dietary advice provided was consistent with current Australian dietary standards [24] in which women are encouraged to maintain a balance of carbohydrates, fat, and protein and reduce their intake of foods high in refined carbohydrates and saturated fats while increasing their intake of fiber, promoting the consumption of 2 servings of fruit, 5 servings of vegetables, and 3 servings of dairy each day [24]. Advice regarding exercise in pregnancy is primarily focused on encouraging women to increase their activity through walking and incidental activity [25]. After randomization, a detailed dietary and physical activity history was obtained from women during an initial planning session with a research dietician. Individualized information was provided, including meal plans, time-saving and easy-to-prepare healthy recipes, advice regarding simple food substitutions (e.g. reducing sugarsweetened soft drinks and fruit juices, reducing added sugar and foods high in refined carbohydrates, and lowfat alternatives), healthy snack and eating-out options, and general guidelines associated with healthy food preparation. At this session, each woman was encouraged to identify and set achievable goals for dietary and exercise changes. Furthermore, they were supported in making these lifestyle changes and self-monitoring their progress utilizing a provided booklet. Specifically, each woman was encouraged to identify potential barriers to them implementing their dietary goals, and using these perceived barriers they were assisted in solving the problem and developing individualized strategies to facilitate their successful implementation.
Dodd
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
costs will continue to double each decade, representing up to 18% of the total health care expenditure by 2030 [6]. The impact of maternal overweight and obesity during pregnancy and childbirth is substantial, with a large proportion of pregnant women being overweight or obese, and estimates have increased from 35% reported in 2006 [7] to more recent figures in the order of 50% or more [8–11]. There are well-documented risks of poor health outcomes associated with obesity during pregnancy, and the risks increase as the BMI increases [7, 9]. Recognized pregnancy complications include an increased risk of hypertension, preeclampsia, gestational diabetes, and the need for both induction of labor and a caesarean section [7, 9, 12]. Furthermore, there is increasing recognition of the health implications of maternal overweight and obesity for the infant. Infants born to women who are overweight or obese are more likely to require nursery admission and treatment for both hypoglycemia and jaundice [7, 9]. These infants are also more likely to have a birth weight above 4 kg [9, 12–14], which in turn has been recognized as a risk factor for subsequent obesity in both childhood and adulthood [15, 16]. Complicating the relationship between the maternal prepregnancy BMI and pregnancy outcomes is the independent effect of gestational weight gain (GWG), which is also associated with many of these same adverse pregnancy outcomes [7, 9, 17, 18]. There is a substantial amount of literature on maternal weight gain in pregnancy that has been summarized by the Institute of Medicine [19, 20]. Since 1970, most studies have reported average weight gains of 10–15 kg, with the rate of gain in the last half of pregnancy ranging from 0.45 to 0.52 kg/week, although this varies considerably among overweight and obese women, with many having GWG exceeding this average [19]. The original focus of the Institute of Medicine recommendations was the relationship between GWG and fetal growth restriction [19] in an era before the widespread prevalence of obesity. These recommendations have since been reviewed [20], recognizing the trade-off that often exists between maternal and infant outcomes [21] and advocating a GWG of 7.0–11.5 kg for women who are overweight and a GWG of 5.0–9.0 kg for women who are obese [20]. It is estimated that more than 60% of pregnant women report a weight gain in excess of the Institute of Medicine recommendations [20]. In view of the association between obesity and GWG, there has been intense research interest in the evaluation of interventions, particularly among women who are overweight or obese, to limit GWG.
assessment of the participants has been undertaken (and completed) at 6 and 18 months of age, with follow-up at age 3 years currently ongoing. The Pedersen hypothesis, also known as the developmental overnutrition hypothesis [30], was proposed as a possible explanation for the relationship observed between maternal diabetes in pregnancy and increased fetal adiposity or overgrowth. It was postulated that maternal hyperglycemia contributed to increased transplacental glucose transfer, with subsequent fetal hyperglycemia and increased insulin production. The overall net effect of fetal hyperinsulinemia was an increase in insulin-mediated fetal growth. Subsequently, the role of other fuel substrates, including free fatty acids, triglycerides, and amino acids, was also recognized [30]. In recent times, the fetal developmental overnutrition hypothesis has been expanded in recognition of the potentially significant metabolic impact of maternal obesity [31]. Furthermore, there is increasing evidence to support an effect of maternal obesity on direct alterations in the placental transfer of metabolic substrates. Both maternal overweight and obesity are risk factors for the subsequent development of gestational diabetes [7, 9, 32]. Metabolically, obesity and gestational diabetes share similar characteristics, including insulin resistance, hyperglycemia, hyperlipidemia, and a low-grade state of chronic inflammation, which in turn has been shown to alter the availability and the placental transfer of nutrients to the developing fetus [31]. Adipose tissue also has a critical role in innate immune sensing, with various adipocytokines (leptin, TNF-α, and IL-6) acting to antagonize the effects of insulin [33–38]. Through manipulation of the maternal diet during pregnancy and early postnatal feeding, animal studies have identified significant alterations in offspring body composition and adiposity, potentially mediated through modification of appetite and energy expenditure [39–41]. In rodents, diet-induced maternal obesity has been shown to cause obesity, diabetes, and fatty liver disease, as well as behavior and learning changes in offspring [42]. The effects of maternal dietary modification during pregnancy on infant body composition and metabolic health are less clear. Cohort studies have suggested, despite minimal changes in birth weight, that infants born to women who are overweight or obese have an increased percentage of body fat and fat mass compared to infants born to women with a normal BMI [43–45]. Similarly, infants born to women with gestational diabetes have been demonstrated to have an increased fat mass and a reduced lean tissue mass at birth, again despite minimal
The LIMIT Trial
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
199
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
This information was reinforced during subsequent inputs across pregnancy provided by the research dietician (at 28 weeks’ gestation) and trained research assistants (via telephone contact at 22, 24, and 32 weeks’ gestation and a face-to-face visit at 36 weeks’ gestation). Women who were randomized to receiving standard care continued their pregnancy care according to statewide perinatal practice and local hospital guidelines, which did not include routine provision of dietary or exercise advice or information regarding GWG targets [26]. Outcomes focused on a range of maternal and infant clinical outcomes, in addition to maternal dietary and physical activity changes, maternal psychological wellbeing and quality of life, ultrasound assessment of fetal growth and adiposity, and anthropometry (maternal, paternal, and neonatal). A total of 2,212 women were recruited and randomized to the LIMIT trial. The median BMI of the cohort was 31.1 (IQR 27.9–35.8), with 42.1% of women being overweight and 57.9% obese [22]. Infants born to women who received lifestyle advice were 18% less likely to have a high birth weight (p = 0.04) [22] compared to infants born to women who received standard care. No statistically significant differences were identified between the two groups with regard to maternal antenatal, labor, or birth outcomes [22]. In a post hoc analysis, the mean GWG of approximately 9.4 kg did not differ between the two treatment groups, with GWG above the Institute of Medicine recommendations for approximately 42% of all women [22]. Despite the lack of a difference in GWG between the two treatment groups, women who received lifestyle advice were successful in making significant changes to both their diet and their physical activity [Dodd et al., unpubl. data]. The findings of the LIMIT randomized trial [22] provide evidence that changes in maternal diet and physical activity during pregnancy can reduce the risk of high infant birth weight among women who are overweight or obese. This is of great significance given the observational data from the US Early Childhood Longitudinal Study [27], which highlights that children with a birth weight greater than 4 kg are at a significantly greater risk for obesity in adolescence. In that cohort, while the incidence of birth weight over 4 kg was 12%, 36% of individuals who were obese at age 14 years had a birth weight over 4 kg [27]. Therefore, any antenatal intervention that is successful in reducing the risk of high infant birth weight potentially represents a significant strategy to tackle obesity from a population health perspective [28, 29], with ongoing follow-up of participants from the LIMIT randomized trial into childhood being essential. To this end,
Table 1. Specimen/measurement and time point of collection
Type
Time point
Anthropometric measure
Biological specimen
Maternal
Trial entry and 36 weeks’ GA 28 weeks’ GA
Weight, height, BMI BC, and SFTM
Cardiometabolic responsea Buffy coat: genetic analysesb Cardiometabolic responsea
Weight, height, BMI BC, and SFTM
Saliva: genetic analysesb
Paternal Fetal
28 and 36 weeks’ GA
Ultrasound fetal growth and adiposity measures
Neonatal
Birth
Weight, length, BMI BC, SFTM, and BIA
Cord blood: cardiometabolic responsea Nucleated blood cells: genetic analysesb
Infant
6, 18, and 36 months
Weight, length/height, BMI BC, SFTM, and BIA
Saliva: genetic analysesb
differences in birth weight [46, 47]. Furthermore, there are reports indicating that these differences in the distribution of adipose tissue persist into early childhood [48, 49]. The maternal dietary fat intake during pregnancy also appears to impact childhood adiposity, with a diet high in polyunsaturated fatty acids being associated with reduced childhood adiposity as measured by skinfold thickness [50], in addition to predicting the fat mass as measured by DEXA scans in children aged 4 and 6 years [51]. Features of the metabolic syndrome, specifically abdominal adiposity, hypertension, and type 2 diabetes, are being increasingly linked to changes in the intrauterine environment and epigenetic modification of gene expression and subsequent changes in body composition in fetal life and early infancy, reflecting altered ratios of fat and lean tissue mass, as well as changes in metabolic pathway regulation [52]. The well-described features of the metabolic syndrome in adults have been documented increasingly in children [1, 53–55], with population studies indicating that 25% of 8-year-old and 29% of 14-yearold children have features of the syndrome [53]. The effect of maternal obesity and GWG on the risk of a subsequent cardiovascular risk and hypertension in offspring is also emerging, with both maternal prepregnancy obesity and high degrees of GWG documented to be associated with an altered cardiovascular risk profile and a higher blood pressure in children [15, 56]. While these 200
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
associations have not been universally reported [42, 57, 58], some suggest that the changes remain evident up until 21 years of age [59]. While observational studies have indicated an association between both a high maternal BMI and a high GWG and the subsequent risk of childhood obesity and cardiometabolic disease, the precise operational mechanisms that contribute to this are unclear. The recent consensus statement from the International Life Sciences Institute, Europe [60], relating to obesity in pregnancy recommended that: ‘assessment of relationships between maternal obesity and offspring health would be facilitated by … long-term follow-up without interruption throughout childhood and into adulthood, determination of parental, neonatal and childhood adiposity and fat distribution, … measurement of growth trajectories in the fetus, … collection of paternal, maternal, and child DNA, in addition to maternal and cord blood biomarkers’ [60]. As outlined in table 1, much of this extensive range of biospecimens and measurements has been prospectively collected within the context of the LIMIT randomized trial which, in combination with ongoing childhood assessment, will provide a unique and invaluable resource facilitating evaluation of the mechanistic pathways of maternal-toinfant/childhood obesity. Both a high maternal BMI [7, 9] and a high GWG [17, 18] have been recognized as significant and independent predictors of future child and adult obesity [61–64]. Dodd
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
GA = Gestational age; BC = body circumferences; BIA = bioimpedance analysis; SFTM = skin fold thickness measurement. a Includes carbohydrate metabolism, triglycerides, and adipocytokines. b Include both genetic and epigenetic evaluations.
While the association between maternal and infant and childhood adiposity is likely to reflect a combination of shared genetic and environmental factors in addition to in utero programming pathways, the latter may be modifiable and therefore of enormous significance as a strategy to prevent or limit the early onset of obesity. The clinical findings of the LIMIT randomized trial, and the subsequent detailed evaluation of mechanistic information, will continue to providing unique opportunities to evaluate the contribution of the intrauterine environment to the pathways between maternal and child obesity.
Acknowledgement This article reports an extended version of the presentation made at the conference ‘The Power of Programming 2014. International Conference on Developmental Origins of Adiposity and Long-Term Health’, held in Munich on March 13–15, 2014. To participate in the conference, the author received funding from the European Union’s 7th Framework Programme (FP7/2007–2013), EarlyNutrition project, under grant agreement No. 289346.
Disclosure Statement The author has no financial interests to disclose.
References
The LIMIT Trial
13 Cedergren MI: Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol 2004;103:219–224. 14 Cnattingius S, Bergstrom R, Lipworth L, Kramer MS: Prepregnancy weight and the risk of adverse pregnancy outcomes. N Engl J Med 1998;338:147–152. 15 Fraser A, Tilling K, Macdonald-Wallis C, Sattar N, Brion MJ, Benfield L, et al: Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation 2010; 121: 2557–2564. 16 Tikellis G, Ponsonby AL, Wells JC, Pezic A, Cochrane J, Dwyer T: Maternal and infant factors associated with neonatal adiposity: results from the Tasmanian Infant Health Survey. Int J Obes 2012;36:496–504. 17 Cedergren MI: Effects of gestational weight gain and body mass index on obstetric outcomes in Sweden. Int J Gynaecol Obst 2006; 93:269–274. 18 Cedergren MI: Optimal gestational weight gain for body mass index categories. Obstet Gynecol 2007;110:759–764. 19 Institute of Medicine: Nutrition during Pregnancy. Washington, National Academies Press, 1990. 20 Institute of Medicine: Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, National Academies Press, 2009. 21 Rasmussen KM, Abrams B, Bodnar LM, Butte NF, Catalano PM, Siega-Riz AM: Recommendations for weight gain during pregnancy in the context of the obesity epidemic. Obstet Gynecol 2010;116:1191–1195. 22 Dodd JM, Turnbull DA, McPhee AJ, Deussen AR, Grivell RM, Yelland LN, et al: Antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial. BMJ 2014;348:g1285. 23 Dodd JM, Turnbull DA, McPhee AJ, Wittert G, Crowther CA, Robinson JS: Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial. BMC Pregnancy Childbirth 2011;11:79.
24 Australian Guide to Healthy Eating. http:// www.health.gov.au/internet/main/publishing.nsf/content/health-pubhlth-publicatdocument-fdcons-cnt.htm. 25 Royal College of Obstetricians and Gynaecologists: Recreational exercise and pregnancy: information for you. London, RCOG Press, 2006. 26 South Australian Perinatal Guidelines: normal pregnancy, labour and puerperium. 2007. http://www.health.sa.gov.au/ppg/Default. aspx?PageContentID=2248&tabid = 54%5D. 27 Cunningham SA, Kramer MR, Narayan KM: Incidence of childhood obesity in the United States. N Engl J Med 2014;370:403–411. 28 Catalano PM: Obesity and pregnancy – the propagation of a viscous cycle? J Clin Endocrinol Metab 2003;88:3505–3506. 29 Poston L: Healthy eating in pregnancy – always a good idea, now with more supporting evidence. BMJ 2014;348:g1739. 30 Pedersen J: Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica 1954;16:330–342. 31 Catalano PM, Hauguel-De Mouzon S: Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am J Obstet Gynecol 2011;204:479–487. 32 Athukorala C, Crowther CA, Willson K: Women with gestational diabetes mellitus in the ACHOIS trial: risk factors for shoulder dystocia. Aust NZ J Obstet Gynaecol 2007;47: 37–41. 33 Sjoholm A, Nystrom T: Endothelial inflammation in insulin resistance. Lancet 2005;365: 610–613. 34 Han TS, Sattar N, Williams K, GonzalezVillalpando C, Lean ME, Haffner SM: Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 2002;25:2016–2021. 35 Duncan BB, Schmidt MI, Pankow JS, et al: Low-grade systemic inflammation and the development of type 2 diabetes. Diabetes 2003;52:1799–1805.
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
201
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
1 Cali AM, Caprio S: Obesity in children and adolescents. J Clin Endocrinol Metab 2008; 93:S31–S36. 2 World Health Organization: WHO obesity and overweight fact sheet (No 311). 2006 http://www.who.int/mediacentre/factsheets/ fs311/en/print.html. 3 Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ; Comparative Risk Assessment Collaborating Group: Selected major risk factors and global and regional burden of disease. Lancet 2002;360:1347–1360. 4 Access Economics: The Growing Cost of Obesity in 2008: Three Years On. Canberra, Diabetes Australia, 2008. 5 Roehr B: ‘Soda tax’ could help tackle obesity, says US director of public health. BMJ 2009; 339:b3176. 6 Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK: Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity 2008;16:2323–2330. 7 Callaway LK, Prins JB, Chang AM, McIntyre HD: The prevalence and impact of overweight and obesity in an Australian obstetric population. Med J Aust 2006;184:56–59. 8 Scheil W, Scott J, Catcheside B, Sage L: Pregnancy Outcome in South Australia 2010. Adelaide, SA Health 2012. 9 Dodd JM, Grivell RM, Nguyen A-M, Chan A, Robinson JS: Maternal and perinatal health outcomes by body mass index category. Aust NZ J Obstet Gynaecol 2011;51:136–140. 10 Chu SY, Kim SY, Bish CL: Prepregnancy obesity prevalence in the United States, 2004– 2005. Matern Child Health J 2009;13:614–620. 11 NICE issues pregnancy weight management guidance, as the number of obese mothers soars. 2010. http://www.nice.org.uk/newsroom/news/NICEissuesPregnancyWeightManagementGuideance. 12 Abenhaim HA, Kinch RA, Morin L, Benjamin A, Usher R: Effect of prepregnancy body mass index categories on obstetrical and neonatal outcomes. Arch Gynecol Obstet 2007; 275: 39–43.
202
47 Catalano PM, Kirwan JP, Haugel-de Mouzon S, King J: Gestational diabetes and insulin resistance: role in short and long-term implications for mother and fetus. J Nutr 2003; 133: 1674S–1683S. 48 Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators: Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003– 2015. 49 Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM: Metformin in gestational diabetes: the offspring follow-up (MiG TOFU) – body composition at 2 years of age. Diabetes Care 2011;34:2279–2284. 50 Donahue SM, Rifas-Shiman SL, Gold DR, Jouni ZE, Gillman MW, Oken E: Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort. Am J Clin Nutr 2011;93:780–788. 51 Moon RJ, Harvey NC, Robinson SM, Ntani G, Davies JH, Inskip HM, et al: Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. J Clin Endocrinol Metab 2013;98:299–307. 52 James WP: The epidemiology of obesity: the size of the problem. J Intern Med 2008; 263: 336–352. 53 Beillin L, Huang RC: Childhood obesity, hypertension, the metabolic syndrome and adult cardiovascular disease. Clin Exp Pharmacol Physiol 2008;35:409–411. 54 Bokor S, Frelut ML, Vania A, Hadjiathanasiou CG, Anastassakou M, Malecka-Tendera E, et al: Prevalence of metabolic syndrome in European obese children. Int J Pediatr Obes 2008;3:3–8. 55 Seki M, Matsuo T, Caria Carrilho AJ: Prevalence of metabolic syndrome and associated risk factors in Brazilian school children. Public Health Nutr 2009;12:947–952. 56 Oken E, Taveras EM, Kleinman KP, Rich-Edwards JW, Gillman MW: Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol 2007;196:322–328.
Ann Nutr Metab 2014;64:197–202 DOI: 10.1159/000365018
57 Godfrey KM, Forrester T, Barker DJ, Jackson AA, Landman JP, Hall JS, et al: Maternal nutritional status in pregnancy and blood pressure in childhood. Br J Obstet Gynaecol 1994; 101:398–403. 58 Clark PM, Atton C, Law CM, Shiell A, Godfrey K, Barker DJ: Weight gain in pregnancy, triceps skinfold thickness, and blood pressure in offspring. Obstet Gynecol 1998; 91: 103– 107. 59 Mamun AA, Kinarivala M, O’Callaghan MJ, Williams GM, Najman JM, Callaway LK: Associations of excess weight gain during pregnancy with long-term maternal overweight and obesity: evidence from 21 y postpartum follow-up. Am J Clin Nutr 2010; 91: 1336– 1341. 60 Poston L, Harthoorn LF, Van Der Beek EM; Contributirs to the ILSI Europe Workshop: Obesity in pregnancy: implications for the mother and lifelong health of the child – a consensus statement. Pediatr Res 2011; 69: 175–180. 61 Godfrey KM, Inskip HM, Hanson MA: The long-term effects of prenatal development on growth and metabolism. Semin Reprod Med 2011;29:257–265. 62 Wells JC, Haroun D, Levene D, Darch T, Williams JE, Fewtrell MS: Prenatal and postnatal programming of body composition in obese children and adolescents: evidence from anthropometry, DXA and the 4-component model. Int J Obes 2011;35:534–540. 63 Winter JD, Langenberg P, Krugman SD: Newborn adiposity by body mass index predicts childhood overweight. Clin Pediatr 2010;49:866–870. 64 Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C: Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 2005;331:929.
Dodd
Downloaded by: Selçuk Universitesi 193.255.248.150 - 1/18/2015 11:35:19 AM
36 Lyon CJ, Law RE, Hsueh WA: Minireview: adiposity, inflammation and atherogenesis. Endocrinology 2003;144:2195–2200. 37 Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM: C-reactive protein, interleukin-6 and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327–334. 38 Greenberg AS, Obin MS: Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:461–465. 39 Robinson SM, Godfrey KM: Feeding practices in pregnancy and infancy: relationship with the development of overweight and obesity in childhood. Int J Obes 2008;32:S4–S10. 40 Simmons R: Perinatal programming of obesity. Semin Perinatol 2008;32:371–374. 41 Gluckman PD, Hanson MA, Cooper C, Thornburg KL: Effect of in utero and earlylife conditions on adult health and disease. N Engl J Med 2008;359:61–73. 42 Laor A, Stevenson DK, Shemer J, Gale R, Seidman DS: Size at birth, maternal nutritional status in pregnancy, and blood pressure at age 17: population based analysis. BMJ 1997;315: 449–453. 43 Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole ZA, et al: Weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr 2010;91:1745–1751. 44 Hull HR, Dinger MK, Knehans AW, Thompson DM, Fields DA: Impact of maternal body mass index on neonate birth weight and body composition. Am J Obstet Gynecol 2008;198: 416.e1–416.e6. 45 Sewell MF, Huston-Presley L, Super DM, Catalano PM: Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. Am J Obstet Gynecol 2006;195:1100– 1103. 46 Durnwald CP, Ehrenberg HM, Mercer BM: The impact of maternal obesity and weight gain in vaginal birth after caesarean section success. Am J Obstet Gynecol 2004; 191: 954– 957.
