The Journal of Nutrition. First published ahead of print June 7, 2017 as doi: 10.3945/jn.117.250639. The Journal of Nutrition Nutritional Epidemiology
Maternal Night-Fasting Interval during Pregnancy Is Directly Associated with Neonatal Head Circumference and Adiposity in Girls but Not Boys See Ling Loy,1,6 Poh Hui Wee,2 Marjorelee T Colega,9 Yin Bun Cheung,5,10 Izzuddin M Aris,9 Jerry Kok Yen Chan,1,6 Keith M Godfrey,11,12 Peter D Gluckman,9,13 Kok Hian Tan,3 Lynette Pei-Chi Shek,14,17 Yap-Seng Chong,9,15 Padmapriya Natarajan,15 Falk Mu¨ller-Riemenschneider,16,18 Ngee Lek,2,6 Victor Samuel Rajadurai,4 Mya-Thway Tint,14,15 Yung Seng Lee,7,14,17 Mary Foong-Fong Chong,8,9,16 and Fabian Yap2,6,19 Downloaded from jn.nutrition.org at CORNELL UNIV WEILL MEDICAL COLLEGE on June 10, 2017
Departments of 1Reproductive Medicine, 2Paediatrics, 3Maternal Fetal Medicine, and 4Neonatology, KK WomenÕs and ChildrenÕs Hospital, Singapore; 5Center for Quantitative Medicine, 6Duke-NUS Medical School, Singapore; 7Brenner Centre for Molecular Medicine and 8Clinical Nutrition Research Centre, 9Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore; 10Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; 11Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom; 12National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom; 13Liggins Institute, University of Auckland, Auckland, New Zealand; Departments of 14Paediatrics and 15 Obstetrics and Gynaecology, Yong Loo Lin School of Medicine and 16Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 17Khoo Teck Puat-National University ChildrenÕs Medical Institute, National University Hospital, National University Health System, Singapore; 18Institute for Social Medicine, Epidemiology and Health Economics, Charite University Medical Centre, Berlin, Germany; and 19Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
Abstract Background: Synchrony between daily feeding-fasting signals and circadian rhythms has been shown to improve metabolic health in animals and adult humans, but the potential programming effect on fetal growth is unknown. Objective: We examined the associations of the maternal night-fasting interval during pregnancy with offspring birth size and adiposity. Methods: This was a cross-sectional study of mother-offspring dyads within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. For 384 mothers aged 30.8 6 4.8 y (mean 6 SD), the night-fasting interval at 26–28 wk of gestation was determined from a 3-d food diary based on the average of the fasting duration at night (1900–0659). Offspring birth weight, length, and head circumference were measured and converted to weight-for-gestational age (GA), length-for-GA, and head circumference–for-GA z scores, respectively, by using local customized percentile charts. The percentage of neonatal total body fat (TBF) was derived by using a validated prediction equation. Multivariable general linear models, stratified by child sex, were performed. Results: The mean 6 SD maternal night-fasting interval was 9.9 6 1.3 h. In infant girls, each 1-h increase in the maternal night-fasting interval was associated with a 0.22-SD (95% CI: 0.05-, 0.40-SD; P = 0.013) increase in birth head circumference–for-GA and a 0.84% (95% CI: 0.19%, 1.49%; P = 0.012) increase in TBF at birth, after adjustment for confounders. In infant boys, no associations were observed between the maternal night-fasting interval and birth size or TBF. Conclusions: An increased maternal night-fasting interval in the late second trimester of pregnancy is associated with increased birth head circumference and TBF in girls but not boys. Our findings are in accordance with previous observations that suggest that there are sex-specific responses in fetal brain growth and adiposity, and raise the possibility of the maternal night-fasting interval as an underlying influence. This trial was registered at clinicaltrials.gov as NCT01174875. J Nutr doi: https://doi.org/10.3945/jn.117.250639
Keywords: birth outcomes, food timing, head circumference, obesity, pregnancy diet
Introduction Over time, living things have developed intrinsic timing systems of circadian rhythmicity that orchestrate multiple cellular functions necessary for life (1). Under the influence of light-dark
cycles, these rhythms have evolved to accommodate the bodyÕs dependence on alternate periods of feeding and fasting (2). Indeed, synchrony between circadian rhythms and feedingfasting signals ensure that anabolic and catabolic pathways are
ã 2017 American Society for Nutrition. Manuscript received March 8, 2017. Initial review completed April 18, 2017. Revision accepted May 10, 2017. doi: https://doi.org/10.3945/jn.117.250639
Copyright (C) 2017 by the American Society for Nutrition
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Methods Study design and participants. Data were drawn from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) study (clinicaltrials.gov Supported by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of HealthÕs National Medical Research Council (NMRC) (grants NMRC/TCR/004-NUS/2008 and NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research. YBC is supported by the Singapore National Research Foundation under its Clinician Scientist Award (award NMRC/CSA/0039/2012) administered by the Singapore Ministry of HealthÕs NMRC. JKYC received salary support from the Ministry of HealthÕs NMRC (grant NMRC/CSA/043/2012). KMG was supported by the NIH Research through the NIHR Southampton Biomedical Research Centre and the European UnionÕs Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement 289346. Author disclosures: SLL, PHW, MTC, YBC, IMA, JKYC, KHT, LP-CS, PN, FM-R, NL, VSR, M-TT, and MF-FC, no conflicts of interest. KMG, PDG, Y-SC, YSL, and FY have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG, PDG, and Y-SC are part of an academic consortium that has received research funding from Abbott ´ and Danone. Nutrition, Nestle, Supplemental Table 1 is available from the ‘‘Online Supporting Material’’ link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org. MF-FC and FY were joint senior authors for this work. Address correspondence to FY (e-mail: [email protected]). Abbreviations used: GA, gestational age; GDM, gestational diabetes mellitus; GUSTO, Growing Up in Singapore Towards healthy Outcomes; GWG, gestational weight gain.
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Loy et al.
identifier NCT01174875). Details of the GUSTO study have been provided elsewhere (12). This study was conducted according to the guidelines in the Declaration of Helsinki. Ethical approval was obtained from the Domain Specific Review Board of the Singapore National Healthcare Group (reference D/09/021) and the SingHealth Centralised Institutional Review Board (reference 2009/280/D). Pregnant women who received antenatal care (
Maternal Night-Fasting Interval during Pregnancy Is Directly Associated with Neonatal Head Circumference and Adiposity in Girls but Not Boys See Ling Loy,1,6 Poh Hui Wee,2 Marjorelee T Colega,9 Yin Bun Cheung,5,10 Izzuddin M Aris,9 Jerry Kok Yen Chan,1,6 Keith M Godfrey,11,12 Peter D Gluckman,9,13 Kok Hian Tan,3 Lynette Pei-Chi Shek,14,17 Yap-Seng Chong,9,15 Padmapriya Natarajan,15 Falk Mu¨ller-Riemenschneider,16,18 Ngee Lek,2,6 Victor Samuel Rajadurai,4 Mya-Thway Tint,14,15 Yung Seng Lee,7,14,17 Mary Foong-Fong Chong,8,9,16 and Fabian Yap2,6,19 Downloaded from jn.nutrition.org at CORNELL UNIV WEILL MEDICAL COLLEGE on June 10, 2017
Departments of 1Reproductive Medicine, 2Paediatrics, 3Maternal Fetal Medicine, and 4Neonatology, KK WomenÕs and ChildrenÕs Hospital, Singapore; 5Center for Quantitative Medicine, 6Duke-NUS Medical School, Singapore; 7Brenner Centre for Molecular Medicine and 8Clinical Nutrition Research Centre, 9Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore; 10Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; 11Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom; 12National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom; 13Liggins Institute, University of Auckland, Auckland, New Zealand; Departments of 14Paediatrics and 15 Obstetrics and Gynaecology, Yong Loo Lin School of Medicine and 16Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 17Khoo Teck Puat-National University ChildrenÕs Medical Institute, National University Hospital, National University Health System, Singapore; 18Institute for Social Medicine, Epidemiology and Health Economics, Charite University Medical Centre, Berlin, Germany; and 19Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
Abstract Background: Synchrony between daily feeding-fasting signals and circadian rhythms has been shown to improve metabolic health in animals and adult humans, but the potential programming effect on fetal growth is unknown. Objective: We examined the associations of the maternal night-fasting interval during pregnancy with offspring birth size and adiposity. Methods: This was a cross-sectional study of mother-offspring dyads within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. For 384 mothers aged 30.8 6 4.8 y (mean 6 SD), the night-fasting interval at 26–28 wk of gestation was determined from a 3-d food diary based on the average of the fasting duration at night (1900–0659). Offspring birth weight, length, and head circumference were measured and converted to weight-for-gestational age (GA), length-for-GA, and head circumference–for-GA z scores, respectively, by using local customized percentile charts. The percentage of neonatal total body fat (TBF) was derived by using a validated prediction equation. Multivariable general linear models, stratified by child sex, were performed. Results: The mean 6 SD maternal night-fasting interval was 9.9 6 1.3 h. In infant girls, each 1-h increase in the maternal night-fasting interval was associated with a 0.22-SD (95% CI: 0.05-, 0.40-SD; P = 0.013) increase in birth head circumference–for-GA and a 0.84% (95% CI: 0.19%, 1.49%; P = 0.012) increase in TBF at birth, after adjustment for confounders. In infant boys, no associations were observed between the maternal night-fasting interval and birth size or TBF. Conclusions: An increased maternal night-fasting interval in the late second trimester of pregnancy is associated with increased birth head circumference and TBF in girls but not boys. Our findings are in accordance with previous observations that suggest that there are sex-specific responses in fetal brain growth and adiposity, and raise the possibility of the maternal night-fasting interval as an underlying influence. This trial was registered at clinicaltrials.gov as NCT01174875. J Nutr doi: https://doi.org/10.3945/jn.117.250639
Keywords: birth outcomes, food timing, head circumference, obesity, pregnancy diet
Introduction Over time, living things have developed intrinsic timing systems of circadian rhythmicity that orchestrate multiple cellular functions necessary for life (1). Under the influence of light-dark
cycles, these rhythms have evolved to accommodate the bodyÕs dependence on alternate periods of feeding and fasting (2). Indeed, synchrony between circadian rhythms and feedingfasting signals ensure that anabolic and catabolic pathways are
ã 2017 American Society for Nutrition. Manuscript received March 8, 2017. Initial review completed April 18, 2017. Revision accepted May 10, 2017. doi: https://doi.org/10.3945/jn.117.250639
Copyright (C) 2017 by the American Society for Nutrition
1 of 8
Methods Study design and participants. Data were drawn from the GUSTO (Growing Up in Singapore Towards healthy Outcomes) study (clinicaltrials.gov Supported by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of HealthÕs National Medical Research Council (NMRC) (grants NMRC/TCR/004-NUS/2008 and NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research. YBC is supported by the Singapore National Research Foundation under its Clinician Scientist Award (award NMRC/CSA/0039/2012) administered by the Singapore Ministry of HealthÕs NMRC. JKYC received salary support from the Ministry of HealthÕs NMRC (grant NMRC/CSA/043/2012). KMG was supported by the NIH Research through the NIHR Southampton Biomedical Research Centre and the European UnionÕs Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement 289346. Author disclosures: SLL, PHW, MTC, YBC, IMA, JKYC, KHT, LP-CS, PN, FM-R, NL, VSR, M-TT, and MF-FC, no conflicts of interest. KMG, PDG, Y-SC, YSL, and FY have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG, PDG, and Y-SC are part of an academic consortium that has received research funding from Abbott ´ and Danone. Nutrition, Nestle, Supplemental Table 1 is available from the ‘‘Online Supporting Material’’ link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org. MF-FC and FY were joint senior authors for this work. Address correspondence to FY (e-mail: [email protected]). Abbreviations used: GA, gestational age; GDM, gestational diabetes mellitus; GUSTO, Growing Up in Singapore Towards healthy Outcomes; GWG, gestational weight gain.
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Loy et al.
identifier NCT01174875). Details of the GUSTO study have been provided elsewhere (12). This study was conducted according to the guidelines in the Declaration of Helsinki. Ethical approval was obtained from the Domain Specific Review Board of the Singapore National Healthcare Group (reference D/09/021) and the SingHealth Centralised Institutional Review Board (reference 2009/280/D). Pregnant women who received antenatal care (
