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Title page
Title: Maternal dietary glycemic index and glycemic load in early pregnancy is associated
with offspring adiposity in childhood: the Southampton Women’s Survey
Authors: Hitomi Okubo, Sarah R Crozier, Nicholas C Harvey, Keith M Godfrey, Hazel M
Inskip, Cyrus Cooper, Siân M Robinson, SWS Study Group
Authors: Okubo, Crozier, Harvey, Godfrey, Inskip, Cooper, Robinson, SWS Study Group
Affiliations: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton,
UK (HO, SRC, NCH, KMG, HMI, CC, SMR); Department of Social and Preventive
Epidemiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan (HO);
NIHR Southampton Biomedical Research Centre, University of Southampton and University
Hospital Southampton NHS Foundation Trust, Southampton, UK (NCH, KMG, SMR, CC);
NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Nuffield Orthopedic
Centre, Headington, Oxford, UK (CC)
Sources of support: This work was supported by grants from the Medical Research Council,
British Heart Foundation, Arthritis Research UK, National Osteoporosis Society, International
Osteoporosis Foundation, Cohen Trust, NIHR Southampton Biomedical Research Centre,
University of Southampton and University Hospital Southampton NHS Foundation Trust, and
NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Participants were
drawn from a cohort study funded by the Medical Research Council and the Dunhill Medical
Trust. The research leading to these results has also received funding from the European
Union's Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant
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agreement n°289346.
Corresponding author: Professor Siân Robinson, MRC Lifecourse Epidemiology Unit,
University of Southampton, Southampton SO16 6YD, UK. Tel: +44 (0)23 8077 7624; Fax:
+44 (0)23 8070 4021; E-mail: [email protected]
Running head: Maternal dietary GI, GL and offspring adiposity
Keywords: Maternal diet; glycaemic index; glycaemic load; adiposity; childhood
Abbreviations used: DXA, dual-energy X-ray absorptiometry; FFQ, food frequency
questionnaire; GI, glycemic index; GL, glycemic load; GWG, gestational weight gain; SWS,
Southampton Women’s Survey
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ABSTRACT
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Background: Maternal hyperglycemia in pregnancy is associated with greater adiposity in
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the offspring. Glycemic index (GI) and glycemic load (GL) describe the glycemic response to
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carbohydrate ingestion. However, the influence of maternal dietary GI and GL in pregnancy
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on childhood adiposity is unknown.
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Objective: We examined relations of maternal dietary GI and GL in early and late pregnancy
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with offspring body composition.
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Design: 906 mother-child pairs from a prospective cohort, the Southampton Women’s Survey,
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were included. Children underwent dual-energy X-ray absorptiometry measurements of body
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composition at birth, 4 or 6 years. Log-transformed fat mass and lean mass were standardized
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with a mean of 0 and SD of 1. Maternal dietary GI and GL were assessed at 11 and 34 weeks'
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gestation using an administered food frequency questionnaire.
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Results: Controlling for potential confounders, both maternal dietary GI and GL in early
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pregnancy were positively associated with fat mass at 4 and 6 years (fat mass SDs per 10-unit
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GI increase: β = 0.43 [95% CI: 0.06, 0.80], P = 0.02 at 4 years; β = 0.40 [95% CI: 0.10, 0.70],
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P = 0.01 at 6 years, fat mass SDs per 50-unit GL increase: β = 0.43 [95% CI: 0.19, 0.67], P <
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0.001 at 4 years, β = 0.27 [95% CI: 0.07, 0.47], P = 0.007 at 6 years). In contrast, there were
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no associations between maternal dietary GI or GL in late pregnancy with offspring fat mass
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at these ages. Maternal dietary GI and GL were not associated with fat mass at birth, or with
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offspring lean mass at any of the ages studied.
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Conclusion: Higher maternal dietary GI and GL in early pregnancy are associated with
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greater adiposity in childhood.
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INTRODUCTION
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Maternal hyperglycemia is linked to greater adiposity and increased risk of obesity in the
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offspring (1, 2). Importantly, treatments to control glycemia in pregnancy have been shown to
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improve these outcomes (3, 4). As maternal blood glucose concentrations are strongly
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influenced by the type of carbohydrate in the diet (5, 6), understanding the role of quality and
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quantity of carbohydrate consumed during pregnancy, and their influence on offspring body
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composition, could bring new insights for preventive strategies for childhood obesity.
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Dietary glycemic index (GI) and glycemic load (GL) have received considerable research
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interest over the past 30 years (7–9) as ways of characterizing the quality and quantity of
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dietary carbohydrate. GI is a relative measure of the blood glucose response to a given
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amount of carbohydrate, that represents the quality of the carbohydrate consumed (10), while
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GL is the product of the GI and the carbohydrate content of the food and thus represents both
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quality and quantity of carbohydrate (11). The associations of maternal dietary GI and GL
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with pregnancy outcomes, such as birthweight, and risk of birth defects have been addressed
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in a few recent studies (12, 13). A diet with a low-GI or GL is hypothesized to have favorable
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effects on maternal glycemic control, due to the slower blood glucose and insulin response
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following consumption. There is some evidence to suggest that a low-GI or low-GL diets
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during pregnancy lower fetal glucose and insulin responses, and have been shown to be linked
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to reduced birthweight and lower fetal adiposity (14, 15). However, not all studies are
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consistent (12). To our knowledge, no previous studies have examined the effects of maternal
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dietary GI and GL in pregnancy on offspring body composition in childhood.
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In this study we describe the associations of maternal dietary GI and GL during
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pregnancy with offspring body composition at birth and childhood, among 906 mother-child
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pairs who participated in a prospective birth cohort, the Southampton Women’s Survey. We
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consider maternal dietary GI and GL assessed in early and late pregnancy, and examine their
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associations with dual-energy X-ray absorptiometry (DXA)-assessed measures of fat and lean
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mass at birth and at 4 and 6 years of age.
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SUBJECTS AND METHODS
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The Southampton Women’s Survey (SWS)
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The SWS is an ongoing, prospective cohort study that was initiated in April 1998, to assess
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the pre-conception characteristics of a general population sample of young women, and to
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investigate a wide range of maternal influences on pregnancy outcome and child health.
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Detailed description of the rationale, study design, and protocol has been published elsewhere
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(16). Briefly, between April 1998 and December 2002, all non-pregnant women aged 20–34 y,
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living in the city of Southampton, United Kingdom, were invited, via their general practitioner,
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to take part in the study. A total of 12,583 women were recruited to the study, 75% of all
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women who were contacted. A trained research nurse visited each woman at home and
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collected information about her health, diet and lifestyle, and performed anthropometric
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measurements. Women in the SWS who subsequently became pregnant were followed up at
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11, 19, and 34 weeks’ gestation; the offspring have been studied in infancy and childhood.
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The SWS was conducted according to the guidelines laid down in the Declaration of
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Helsinki and approved by the Southampton and South West Hampshire Local Research Ethics
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Committee. Written informed consent was obtained from all participating women and by a
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parent or guardian with parental responsibility on behalf of their children.
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Maternal data
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At the initial interview, details of maternal age, educational attainment (defined in six groups
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according to highest academic qualification; (17)) and parity were obtained, and height and
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weight were measured. Among women who became pregnant, smoking status in pregnancy
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was ascertained at the 11- and 34-week interviews. At 34 weeks’ gestation, the research nurses
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weighed the women again. Diet during the preceding 3 months was assessed using an
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interviewer-administered food frequency questionnaire (FFQ) at 11 and 34 weeks’ gestation
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(18). Prompt cards were used to ensure standardized responses to the FFQ. The frequency of
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consumption of foods, which were consumed regularly (≥ once per week), but not listed in the
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FFQ, were also ascertained. Daily volumes and types of milks consumed and amount of sugar
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added to foods were recorded. The FFQ was designed to assess maternal diet in pregnancy. Its
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relative validity was established in comparison with intakes assessed by 4-day food diaries in
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a population of 569 pregnant women, as described previously (18).
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Dietary glycemic index and load in early and late pregnancy
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To calculate maternal dietary GI and GL in early and late pregnancy, GI values were assigned
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to each individual food item in the FFQ and each extra food recorded. GI values were
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obtained from the GI database published by the Medical Research Council Human Nutrition
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Research (MRC HNR), Cambridge, UK, using glucose as reference (GI for glucose 100) (19).
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The database provided direct matches for 83.2% of the foods assessed. For foods that could
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not be matched directly, GI values for similar food items were used as proxies (13.5% of
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foods). If no equivalent food was found (3.3% of foods), an arbitrary value of 70 was
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assigned according to the procedure developed by the MRC HNR (19).
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The GL of each food item was determined by multiplying the carbohydrate content of
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one serving by its GI value (divided by 100). The products for all food items were summed to
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calculate dietary GL (20). The dietary GI was calculated for each participant by dividing their
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dietary GL by their total intake of available carbohydrate.
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Infancy and childhood assessments of body composition, diet and lifestyle
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The children born to the SWS women were followed up at birth and during infancy and
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childhood. At birth, the baby was weighed on calibrated digital scales (Seca, Birmingham,
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UK), and crown-heel length at birth was measured with the use of neonatometer (CMS Ltd).
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Childhood height was measured at ages 4 and 6 years with the use of a portable stadiometer
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(Leicester height measure; Seca Ltd). Within 2 weeks of birth (Lunar DPX-L, .GE Corp,
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Madison, WI, USA) and at 4 and 6 years of age (Hologic Discovery, Hologic Inc. Bedford,
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MA, USA) subsets of children underwent an assessment of body composition by DXA. Total
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and proportionate fat and lean mass were derived from the whole-body scan through the use
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of pediatric software. The total X-ray dose for the whole-body scans were ~10.5 microsieverts
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(pediatric scan mode), which is equivalent to ~1–2 d background radiation. All scan results
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were checked independently by 2 trained operators. The coefficient of variation for body
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composition analysis using the DXA instrument was 1.4–1.9%.
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Details of the milk feeding history over the preceding 6 months were recorded for all
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infants at the 6- and 12-month visits. Duration of breastfeeding was defined according to the
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date of the last breastfeed and categorized into six groups (21). At 3 years of age, diet over the
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preceding 3 months was assessed using an 80-item FFQ that was administered by trained
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research nurses (22). Dietary GI and GL at 3 years of age were calculated using the same
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procedure as maternal dietary GI and GL, as described above. Of the foods listed on the FFQ,
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82.7% of the foods were directly matched to GI values of the MRC HNR database provided,
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16.6% of foods used those of similar foods as proxies and 0.6% of the foods used an arbitrary
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value of 70 (19). Physical activity was assessed as the reported time the child was actively on
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the move (i.e. very energetic activity including ball games, gym club, cycling and swimming)
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each day.
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Statistical analysis
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A total of 1981 women became pregnant and delivered a live-born singleton infant before the
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end of 2003. The exclusions applied were: infants who died in the neonatal period (n = 6),
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who had major congenital growth abnormalities (n = 2), or who were born before 37 weeks’
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gestation (n = 124); mothers who did not have dietary data collected in both early and late
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pregnancy (n = 492). Of the remaining 1430 mother-offspring pairs, 906 children who had
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acceptable whole-body DXA scans at any time point of birth, 4 or 6 years were included in
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the final analysis: 497 children had DXA data at birth, 480 children at 4 years and 580
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children at 6 years of age; 161 children were measured at all three time points.
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Descriptive data are presented as mean (standard deviation), or median (interquartile
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range) for continuous variables and percentages of subjects for categorical variables. The
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values of nutrient intake and dietary GI and GL were adjusted for total energy intake using the
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residual method (23). Maternal nutrient and food intakes in early and late pregnancy were
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compared by using Wilcoxon’s Signed Rank test. Spearman correlation was used to describe
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the relations of nutrient intakes with dietary GI and GL at each time point. Univariate and
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multiple linear regression analyses were performed to explore the associations of maternal
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dietary GI and GL in early and late pregnancy with offspring body composition outcomes at
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birth, 4 and 6 years. Variables of fat mass at all time points were positively skewed and thus
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were log transformed before analyses. For ease of interpretation, these values were
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standardized (mean = 0, SD = 1), as were lean mass variables to allow comparison between
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measures. Body fat mass and lean mass were dependent on child’s stature. Therefore, body
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composition measurements at birth were adjusted for sex, gestational length, age at
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measurement and crown-heel length, and those at 4 and 6 years were adjusted for sex, age at
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measurement and height. These adjusted outcomes were used throughout the analyses. Results
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are presented as standardized β coefficients which reflect the SD change in outcome per 10-
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unit increase in GI or 50-unit increase in GL. We also consider these associations after taking
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account of a number of potential confounding factors; maternal factors were age at delivery,
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height, prepregnancy BMI, educational attainment, parity, gestational weight gain (GWG)
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(24), smoking status in pregnancy, vitamin D status [serum 25(OH)D] at 34 wk (25), plasma
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n-6 polyunsaturated fatty acid (n-6 PUFA) status at 34 wk (26), intake of dietary fiber in early
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or late pregnancy; offspring factors were birthweight, duration of breastfeeding, physical
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activity and dietary GI (where maternal GI was a predictor in the model) or GL (where
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maternal GL was a predictor) at 3 years of age. In addition, effect modification by maternal
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factors (age, prepregnancy BMI, and GWG) and child factors (sex, birthweight, physical
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activity, and dietary GI and GL) was considered by adding interaction terms to the model.
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Dietary GI and GL were categorized into quarters for presentation purposes. All statistical
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analyses were performed using Stata version 13.0 (Statacorp LP, College Station, TX, USA).
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RESULTS
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Characteristics of study population
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Characteristics of the 906 SWS women and their children who had DXA assessments of body
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composition are shown in Table 1. Compared with SWS mothers who gave birth up to the
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end of 2003, but whose child did not have a DXA assessment (n = 524, data not shown),
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mothers with children who had a DXA assessment (n = 906) were older at delivery (P <
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0.001), had a higher level of educational attainment (P = 0.01), smoked less in pregnancy (P <
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0.001), were primiparous (P = 0.01) and breastfed for longer (P < 0.001). There was no
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difference in maternal prepregnancy BMI, GWG, energy intake, dietary GI, GL in early and
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late pregnancy, or gestational age at birth between the mother-child pairs with and without
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children’s DXA data.
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Maternal dietary intakes in early and late pregnancy
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Maternal dietary intakes in early and late pregnancy are shown in Table 2. With the exception
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of starch intakes, intakes of all nutrients increased significantly between early and late
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pregnancy (all P < 0.01). Dietary GL also increased from early to late pregnancy (P <0.01),
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whereas dietary GI decreased (P <0.01). In terms of ranking, associations of nutrient intakes
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with dietary GI and GL in early and late pregnancy, the correlations were moderate. Dietary
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GI in early pregnancy was positively correlated with GL, carbohydrate and starch intakes, and
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inversely correlated with protein, sugar and dietary fiber intakes. Dietary GL in early
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pregnancy was positively correlated with GI, carbohydrate, sugar and starch intakes, and
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inversely correlated with protein and fat intakes. Comparable relationships with nutrient
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intake were observed in late pregnancy.
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The principal food groups contributing to total dietary GL are shown in Supplemental
Table 1. These were bread, added sugar, preserves and confectionery, fruit and juices,
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crackers, cookies and cakes, breakfast cereals and potatoes. This was similar in early and late
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pregnancy, although there were small changes in the relative contributions for some food
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groups when comparing early and late pregnancy. The relative contributions of added sugar,
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preserves and confectionery, breakfast cereals, potatoes, dairy products and soft drinks
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increased in late pregnancy (all P < 0.05), but the contribution of bread and vegetables
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decreased (P < 0.001). Consumption of these food groups according to quarter of the
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distribution of maternal dietary GI and GL in early and late pregnancy is shown in
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Supplemental Tables 2 and 3. Across the distribution of dietary GI and GL there were
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differences in patterns of consumption of most food groups - the most notable differences
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being two to three-fold increases in consumption of potatoes, soft drinks and sugar &
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confectionery across the distribution of GI and GL (Supplemental Table 2). Similar trends
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were observed in late pregnancy (Supplemental Table 3).
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Associations of maternal dietary GI and GL with offspring body composition
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The associations of maternal dietary GI with offspring body composition at birth, 4 and 6
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years, in early and late pregnancy, are shown in Table 3. There was no association between
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maternal dietary GI in early pregnancy with fat mass at birth, but it was positively associated
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with fat mass at 4 and 6 years. These associations remained after adjustment for potential
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confounding factors. Maternal dietary GI in late pregnancy was also positively associated
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with fat mass at 4 and 6 years, but these associations were not robust to adjustment for
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confounding factors. No associations were observed between maternal dietary GI in early or
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late pregnancy and offspring lean mass at any stage of ages.
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Comparable patterns of association were observed between maternal dietary GL and
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offspring body composition (Table 4). Maternal dietary GL in early pregnancy was strongly
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and positively associated with fat mass at 4 and 6 years, before and after adjustment for
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confounding factors. This is illustrated in Figure 1, where the graded relations of maternal
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dietary GL, as well as dietary GI, with fat mass at 4 and 6 years are evident. As observed for
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dietary GI, there were no independent associations between maternal dietary GL in late
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pregnancy with offspring body composition at any age studied.
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In further analyses, we conducted same analyses for boys and girls separately. Similar
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patterns of associations of dietary GI and GL with body composition were observed (data not
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shown, all P for interaction > 0.10). Additionally, maternal factors (age, prepregnancy BMI,
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gestational weight gain) and child factors (birthweight, breastfeeding, physical activity,
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dietary GI and GL at 3 years) were considered as effect modifiers in the association between
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maternal dietary GI, GL and offspring body composition. However, no interactions were
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identified (data not shown). We also repeated our analyses among the subgroups of mother-
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child pairs who had DXA measurements at all three time points (n = 161) and who had DXA
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measurements at both 4 and 6 years (n = 314), and found similar results (data not shown),
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observing positive associations between maternal dietary GI and GL with offspring adiposity
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in early but not in late pregnancy. As higher dietary GL has previously been shown to be
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associated with GWG (27), GWG might be an intermediate factor in the causal pathway
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between maternal dietary GI/GL and offspring adiposity. We therefore conducted the same
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analysis without adjustment for GWG, but the results did not change materially (data not
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shown).
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DISCUSSION
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Main findings
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The principal finding of the present study was that higher maternal dietary GI and GL were
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associated with offspring body fat mass measured by DXA scans in childhood, but that the
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associations with offspring adiposity depended on the timing in pregnancy. Maternal dietary
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GI and GL in early pregnancy, rather than in later pregnancy, showed a clear positive
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association with fat mass at 4 and 6 years. To our knowledge, the effects of maternal dietary
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GI and GL at different time points during pregnancy in relation to offspring adiposity have not
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been described before. The results from this cohort suggest that variations in the quality and
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quantity of carbohydrate consumed in early pregnancy have implications for offspring
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adiposity in later childhood.
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Comparison with previous studies
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Effects of variation in the quality and/or quantity of carbohydrate consumed during pregnancy
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on fetal growth have been confirmed in a growing number of intervention studies. These
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studies showed that changing to a low-GI diet during pregnancy reduced the risk of giving
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birth to a large-for-gestational-age infant (15) and macrosomia (12) when compared with
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mothers who had a high-GI diet. These data are consistent with the small number of
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observational studies that have examined effects of maternal dietary GI (28) and GL (27) on
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birthweight. In contrast, investigations into effects of maternal dietary GI/GL on neonatal
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adiposity are limited and have yielded inconsistent findings of positive (15, 29) or no (30)
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associations. In the present observational study we did not find an association between
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maternal dietary GI/GL and neonatal adiposity. The reason for differing findings is not clear,
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but, at least partly, may be explained by methodological differences, particularly in the
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assessment of GI and GL across studies, differences in the diets of the study populations, as
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well as potential confounding factors considered, which may make it difficult to compare
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results directly.
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Most previous studies have focused on the short-term effects of maternal dietary GI and
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GL on offspring birth outcomes (such as birth size and risk of birth defects) (12, 13).
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However, a recent study from Denmark examined the relation of maternal dietary GI and GL
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at 30 weeks’ gestation with biomarkers of the metabolic syndrome in offspring at age 20 years
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(31). Maternal dietary GI, but not GL, was associated with higher HOMA-IR, insulin and
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leptin concentrations in the adult offspring; higher maternal GL was associated with greater
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waist circumference (difference per 10-unit GL increase 0.26 cm [95% CI: 0.01, 0.51]),
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although this was only found in the female offspring (3). Although the Danish study differs in
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terms of the timing of exposure to high GI and GL, our finding that maternal dietary GL
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during pregnancy is linked to offspring adiposity in childhood, independent of birth size, is
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consistent with these findings. This may suggest that greater fat mass among the children who
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were exposed to relatively higher maternal dietary GI and GL in early pregnancy was not
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simply due to differences in their growth trajectories. Our findings need replication in other
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studies to confirm these relations of maternal dietary GI and GL in early pregnancy with
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offspring adiposity in childhood.
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The difference in relation of dietary GI and GL according to the time during pregnancy
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The positive association of maternal dietary GI and GL in early pregnancy, but not late
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pregnancy, with offspring adiposity in childhood that we observed in the present study was of
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particular interest. The importance of timing of the diet during pregnancy in the programming
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of adult disease susceptibility has been described in the studies of the offspring from the
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Dutch famine cohort (32). In this case, maternal undernutrition during early gestation was
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associated with higher BMI and waist circumference at the age of 50 years in women,
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whereas BMI did not differ significantly in women exposed famine in mid- or late gestation
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(33). These effects were independent of birth size. Additionally, fetuses exposed to famine in
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early gestation were twice as likely to consume a high-fat diet and to be less active in adult
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life (34), implying that later lifestyles related to obesity such as dietary preferences and
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physical activity may also be influenced by prenatal nutrition. Although our data may be
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consistent with these findings, suggesting that programmed effects on offspring energy
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balance arise in early gestation, the effects we describe are of over- rather than undernutrition.
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Our findings may therefore be more comparable with those of studies comparing maternal
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elevated glucose concentration during pregnancy and offspring body composition, where
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positive associations with neonatal anthropometric characteristics (i.e. ratio of cranial/thoracic
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circumference, LGA and macrosomia) were evident already in early to mid-pregnancy (16-20
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weeks) (35). Put together, these studies suggest that in the period of early pregnancy the
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intrauterine environment may have a role in programming of offspring body composition. The
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mechanisms underlying the associations are not fully known, but exposure to high maternal
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blood glucose may linked to permanent changes in appetite control, neuroendocrine
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functioning, and/or energy metabolism in the developing fetus, thus increasing the risk of
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obesity in later life. Future studies are needed in terms of the role of maternal-placental
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nutrient supply, gene expression and epigenetic processes (36) to clarify the mechanisms
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underlying these associations.
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Strength and limitations of this study
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Strengths of the present study include a prospective design, studying a general population
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sample of mother-offspring pairs from a wide range of sociodemographic backgrounds, with
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comprehensive assessments at multiple time points in pregnancy and childhood, and the use
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of DXA to provide direct measures of fat mass and lean mass. Limitations are that DXA
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measurements were not available for the whole SWS cohort. In comparison with mother
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without available children’s DXA measurement, the subset of mothers tended to be better
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educated, less likely to smoke in pregnancy, older, and to have breastfed for longer. However,
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we adjusted for each of these factors in our statistical models, and unless the associations
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between maternal dietary GI, GL and offspring body composition are different in the
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remainder of the cohort, it is unlikely that selection bias could explain our findings. Secondly,
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there may be some error in the assignment of appropriate dietary GI values. This may partly
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be because of a restricted number of food items in the GI database, the database including
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mainly American and Australian food items, and a lack of information on differences in
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variety of foods, cooking methods, nutrient composition and mixed dishes (19). However, this
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limitation would not fully explain the reason why associations of maternal dietary GI/GL with
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offspring adiposity in childhood were observed only in early pregnancy, not in late pregnancy.
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Thirdly, the ability to estimate total food and nutrient intake remains a challenge in
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epidemiological studies. Although we used a validated food frequency questionnaire which
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was administered by trained researchers, misreporting of food intake is a source of
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measurement error. However, this error would be expected to attenuate associations and we
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do not think that misreporting on the FFQ could explain the associations we describe. Finally,
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we adjusted for a large number of potential confounding factors and other influences on
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offspring adiposity previously described in this cohort (21, 24–26). Whilst the associations
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remained independent, and were robust to adjustment, the possibility of residual confounding
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cannot be ruled out.
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Conclusion
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Maternal dietary GI and GL in early pregnancy were positively associated with offspring
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adiposity in childhood. This effect was not observed in later pregnancy. Further longitudinal
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and intervention studies to reduce dietary GI and GL are needed to confirm these findings and
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to determine the importance of the quality and quantity of carbohydrate consumed before and
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in early pregnancy for preventing childhood obesity.
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Acknowledgment
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We are grateful to the women of Southampton and their children who gave their time to take
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part in these studies and to the research nurses and other staff who collected and processed the
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data.
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The authors’ responsibilities were as follows: HO performed the statistical analysis,
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interpreted the data and wrote the manuscript; SRC advised on the statistical analysis; NCH
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collected the 4 –y outcome data and revised the manuscript; KMG, HMI, CC and SMR were
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responsible for the design and conduct of the Southampton Women’s Survey, data collection
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and revised the manuscript; SMR was responsible for the collection analysis of dietary data,
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and assisted in data interpretation and manuscript preparation. All authors read and approved
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the final version of the manuscript. KMG has received reimbursement for speaking at
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conferences sponsored by companies selling nutritional products and is part of an academic
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consortium that has received research funding from Abbot Nutrition, Nestec and Danone.
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None of the other authors had any potential conflicts of interest.
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25
TABLE 1. Characteristics of the Southampton Women's Survey mothers and children studied
n
Value
Mother
Age at child's birth (years)
906
30.4 (3.7) 1
Prepregnancy BMI (kg/m2)
899
24.4 (22.4-27.7) 2
Height (cm)
904
163.6 (6.3)
Degree qualification or above (%)
215
23.8
Smoked in pregnancy (%)
116
12.8
Primiparous (%)
441
48.7
Gestational weight gain (kg)
851
12.1 (6.3)
Child
Sex, boys (%)
480
Gestational age (weeks)
906
Duration of breastfeeding (%)
Never breastfed
132
<1 month
188
1-3 months
178
4-6 months
176
7-11 months
137
≥12 months
72
Total energy intake at 3-y (kcal/d)
834
Dietary GI at 3-y
834
Dietary GL at 3-y
834
Physical activity at 3-y (hour/d)
834
Anthropometric measurement at birth 3
Weight (kg)
495
Length (cm)
494
3
Ponderal index (kg/m )
492
Fat mass (kg)
497
Lean mass (kg)
497
4
4-y measurements
Weight (kg)
480
Height (cm)
480
BMI (kg/m2)
480
Fat mass (kg)
480
Lean mass (kg)
480
4
6-y measurements
Weight (kg)
579
Height (cm)
576
BMI (kg/m2)
575
Fat mass (kg)
580
Lean mass (kg)
580
GI, glycemic index; GL, glycemic load.
1
Mean, standard deviation in parentheses (all such values).
2
Median, interquartile range in parentheses (all such values).
3
Adjusted for sex and gestational age.
4
Adjusted for sex and age at measurement.
53.0
40.1 (1.2)
15.0
21.3
20.2
19.9
15.5
8.2
1531 (1315-1821)
58.8 (56.1-61.5)
125 (114-136)
2.5 (1.5)
3.5 (0.4)
49.8 (1.8)
28.0 (2.4)
0.50 (0.42-0.63)
2.9 (0.2)
17.3 (16.1-18.7)
104.5 (3.9)
15.8 (15.1-16.7)
4.7 (4.1-5.4)
12.0 (1.4)
23.1 (21.2-25.3)
121.9 (4.9)
15.5 (14.7-16.6)
5.6 (4.7-6.9)
16.7 (2.1)
26
TABLE 2. Nutrient intakes in early and late pregnancy and associations with glycemic index (GI) and glycemic load (GL) among 906 women
studied
Nutrient intake
Spearman correlation with dietary GI and GL 5
Early pregnancy
Late pregnancy
Early pregnancy
Late pregnancy
Change 3
Spearman r 4
1
(at 11 wk)
(at 34 wk)
Nutritional intake
GI
GL
GI
GL
2
***
Glycemic index
59.6 (57.7-61.5)
58.9 (57.1-61.0)
-0.6 (-2.4-1.2)
0.50
0.51
0.56 ***
Glycemic load
170 (158-184)
183 (170-195)
12 (-1-25)
0.45
0.51 ***
0.56 ***
Total energy (kcal/d) 2108 (1766-2495) 2291 (1914-2699) 144 (-161-489)
0.59
***
***
***
Protein (g/d)
82.9 (74.8-90.8)
87.6 (79.2-96.1)
5.5 (-2.8-12.4)
0.57
-0.28
-0.54
-0.35
-0.58 ***
Fat (g/d)
84.5 (78.5-90.9)
92.1 (86.2-98.9)
8.0 (1.5-14.0)
0.49
-0.04
-0.69 ***
-0.02
-0.70 ***
Carbohydrate (g/d)
286 (268-305)
309 (291-326)
23.4 (4.3-41.2)
0.47
0.17 *** 0.92 ***
0.19 ***
0.90 ***
Sugars (g/d)
144 (124-166)
165 (146-189)
23.1 (2.5-42.0)
0.52
-0.22 *** 0.48 ***
-0.21 ***
0.50***
Starch (g/d)
135 (121-151)
136 (121-151)
0.6 (-16.1-17.8)
0.39
0.46 *** 0.31 ***
0.53 ***
0.27 ***
Dietary fiber (g/d)
25.6 (22.4-30.1)
26.4 (22.7-30.7)
0.5 (-2.9-3.7)
0.59
-0.30 ***
0.02
-0.28 ***
-0.04
1
All nutrients (except for total energy intake) are adjusted for total energy intake by residual method.
2
Median, interquartile range in parentheses (all such values).
3
Calculated as intake values in late pregnancy minus values in early pregnancy. All nutritional variables (except for starch) differed significantly
between early and late pregnancy, P <0.01 (Wilcoxon signed-rank test).
4
Spearman correlation coefficient (r) of nutrient intakes between early pregnancy and late pregnancy. (P <0.001 for all correlations).
5
Spearman correlation coefficient (r) with GI or GL at early pregnancy (11 wk) and at late pregnancy (34 wk). *P <0.05, **P <0.01, ***P <0.001.
27
TABLE 3. Relation of maternal dietary glycemic index (GI)1 during pregnancy to offspring body composition at birth, 4 years and 6 years in 906
mother-child pairs from the Southampton Women's Survey
Early pregnancy (at 11 wk)
Late pregnancy (at 34 wk)
3
4
Unadjusted
Adjusted model
Unadjusted 3
Adjusted model 4
P value
P value
P value
Outcomes 2
β (95% CI)
β (95% CI)
β (95% CI) P value
β (95% CI)
Fat mass (SD)
Birth
0.01 (-0.29, 0.31) 0.96
-0.10 (-0.43, 0.24) 0.57
0.28 (-0.03, 0.60) 0.08
0.21 (-0.13, 0.56)
0.23
4 years
0.46 (0.15, 0.77) 0.003
0.43 (0.06, 0.80)
0.02
0.37 (0.04, 0.70) 0.03
0.09 (-0.28, 0.46)
0.62
6 years
0.45 (0.17, 0.73) 0.001
0.40 (0.10, 0.70)
0.01
0.53 (0.24, 0.82) <0.001
0.11 (-0.21, 0.44)
0.49
Lean mass (SD)
Birth
-0.01 (-0.31, 0.28) 0.92
-0.15 (-0.49, 0.19) 0.38
0.03 (-0.28, 0.34) 0.85
-0.01 (-0.36, 0.34) 0.96
4 years
-0.09 (-0.40, 0.22) 0.58
-0.04 (-0.41, 0.34) 0.85
0.12 (-0.21, 0.45) 0.48
0.15 (-0.22, 0.52)
0.43
6 years
-0.12 (-0.40, 0.16) 0.39
-0.18 (-0.50, 0.15) 0.28
0.08 (-0.21, 0.37) 0.60
-0.10 (-0.45, 0.25) 0.58
1
Based on glycemic index of glucose = 100.
2
Neonatal outcomes adjusted for sex, gestation, age at measurement and length; outcomes at 4 and 6 years adjusted for sex, age at measurements
and height.
3
Associations are expressed as regression coefficients (β) (95% CI) for standardized variables (relative change in SD of outcome per 10-unit
increase of maternal dietary GI).
4
Adjusted for maternal age at delivery, height, prepregnancy BMI, educational attainment, parity, gestational weight gain, maternal smoking in
pregnancy, maternal serum 25-hydroxy vitamin D concentration at late pregnancy, maternal plasma n-6 polyunsaturated fatty acid concentration
and maternal dietary fiber intake in early or late pregnancy for neonatal outcomes. Further adjusted for birthweight, duration of breastfeeding,
physical activity at 3 years and dietary GI at 3 years for outcomes at 4 and 6 years.
28
TABLE 4. Relation of maternal dietary glycemic load (GL)1 during pregnancy to offspring body composition at birth, 4 years and 6 years in 906
mother-child pairs from the Southampton Women's Survey
Early pregnancy (at 11 wk)
Late pregnancy (at 34 wk)
3
4
Unadjusted
Adjusted model
Unadjusted 3
Adjusted model 4
P value
P value
P value
P value
Outcomes 2
β (95% CI)
β (95% CI)
β (95% CI)
β (95% CI)
Fat mass (SD)
Birth
-0.01 (-0.20, 0.19) 0.96
-0.00 (-0.23, 0.23) 0.99
0.13 (-0.09, 0.34) 0.24
0.15 (-0.08, 0.38) 0.20
4 years
0.30 (0.09, 0.52) 0.006
0.43 (0.19, 0.67) <0.001
0.08 (-0.11, 0.27) 0.42
0.17 (-0.04, 0.37) 0.11
6 years
0.35 (0.15, 0.54) <0.001 0.27 (0.07, 0.47) 0.007
0.17 (-0.01, 0.34) 0.07
0.05 (-0.14, 0.23) 0.61
Lean mass (SD)
Birth
0.01 (-0.18, 0.21) 0.91
-0.01 (-0.24, 0.23) 0.95
0.12 (-0.10, 0.33) 0.28
0.17 (-0.06, 0.41) 0.15
4 years
0.02 (-0.20, 0.24) 0.85
0.09 (-0.15, 0.33) 0.47
0.06 (-0.14, 0.25) 0.57
0.12 (-0.09, 0.33) 0.26
6 years
0.12 (-0.07, 0.31) 0.23
0.13 (-0.09, 0.34) 0.24
0.04 (-0.14, 0.22) 0.68
0.02 (-0.18, 0.22) 0.81
1
Based on glycemic index of glucose = 100.
2
Neonatal outcomes adjusted for sex, gestation, age at measurement and length; outcomes at 4 and 6 years adjusted for sex, age at measurements
and height.
3
Associations are expressed as regression coefficients (β) (95% CI) for standardized variables (relative change in SD of outcome per 50-unit
increase of maternal dietary GL).
4
Adjusted for maternal age at delivery, height, prepregnancy BMI, educational attainment, parity, gestational weight gain, maternal smoking in
pregnancy, maternal serum 25-hydroxy vitamin D concentration at late pregnancy, maternal plasma n-6 polyunsaturated fatty acid concentration
and maternal dietary fiber intake in early or late pregnancy for neonatal outcomes. Further adjusted for birthweight, duration of breastfeeding,
physical activity at 3 years and dietary GL at 3 years for outcomes at 4 and 6 years.
29
LEGENDS FOR FIGURE
FIGURE 1. Mean (and 95% CI) fat mass at 4 and 6 years according to quarters of dietary
glycemic index (GI) and glycemic load (GL) in early pregnancy.
Fat mass (SD) at 4 and 6 years were adjusted for sex, age at measurements, offspring height,
maternal age at delivery, maternal height, prepregnancy BMI, educational attainment, parity,
gestational weight gain, maternal smoking in pregnancy, maternal serum 25-hydroxy vitamin
D concentration at late pregnancy, maternal plasma n-6 polyunsaturated fatty acid
concentration, maternal dietary fiber intake in early pregnancy, birthweight, duration of
breastfeeding, physical activity at 3 years and dietary GL at 3 years. Median (range) GI
quarters were 56.4 (48.9-57.6), 58.7 (57.7-59.5), 60.5 (59.6-61.4) and 62.9 (61.5-71.7); GL
quarters were 149 (99-157), 164 (158-169), 177 (170-183), and 194 (184-334). Number of
subjects GI quarters were 96, 103, 105, 105 at 4 years and 118, 115, 128 and 131 at 6 years;
number of subjects GL quarters were 100, 91, 115, 103 at 4 years and 122, 112, 127 and 131
at 6 years.