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Breastfeeding may benefit cardiometabolic health of children exposed to increased gestational glycemia in utero

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Abstract

Purpose

There is altered breastmilk composition among mothers with gestational diabetes and conflicting evidence on whether breastfeeding is beneficial or detrimental to their offspring’s cardiometabolic health. We aimed to investigate associations between breastfeeding and offspring’s cardiometabolic health across the range of gestational glycemia.

Methods

We included 827 naturally conceived, term singletons from a prospective mother–child cohort. We measured gestational (26–28 weeks) fasting plasma glucose (FPG) and 2-h plasma glucose (2 hPG) after an oral glucose tolerance test as continuous variables. Participants were classified into 2 breastfeeding categories (high/intermediate vs. low) according to their breastfeeding duration and exclusivity. Main outcome measures included magnetic resonance imaging (MRI)-measured abdominal fat, intramyocellular lipids (IMCL), and liver fat, quantitative magnetic resonance (QMR)-measured body fat mass, blood pressure, blood lipids, and insulin resistance at 6 years old (all continuous variables). We evaluated if gestational glycemia (FPG and 2 hPG) modified the association of breastfeeding with offspring outcomes after adjusting for confounders using a multiple linear regression model that included a ‘gestational glycemia × breastfeeding’ interaction term.

Results

With increasing gestational FPG, high/intermediate (vs. low) breastfeeding was associated with lower levels of IMCL (p-interaction = 0.047), liver fat (p-interaction = 0.033), and triglycerides (p-interaction = 0.007), after adjusting for confounders. Specifically, at 2 standard deviations above the mean gestational FPG level, high/intermediate (vs. low) breastfeeding was linked to lower adjusted mean IMCL [0.39% of water signal (0.29, 0.50) vs. 0.54% of water signal (0.46, 0.62)], liver fat [0.39% by weight (0.20, 0.58) vs. 0.72% by weight (0.59, 0.85)], and triglycerides [0.62 mmol/L (0.51, 0.72) vs. 0.86 mmol/L (0.75, 0.97)]. 2 hPG did not significantly modify the association between breastfeeding and childhood cardiometabolic risk.

Conclusion

Our findings suggest breastfeeding may confer protection against adverse fat partitioning and higher triglyceride concentration among children exposed to increased glycemia in utero.

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Data availability

Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.

Code availability

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Acknowledgements

We thank all GUSTO participants as well as the GUSTO study group, which includes Allan Sheppard, Amutha Chinnadurai, Anne Eng Neo Goh, Anne Rifkin-Graboi, Anqi Qiu, Arijit Biswas, Bee Wah Lee, Birit F.P. Broekman, Boon Long Quah, Borys Shuter, Chai Kiat Chng, Cheryl Ngo, Choon Looi Bong, Christiani Jeyakumar Henry, Claudia Chi, Cornelia Yin Ing Chee, Yam Thiam Daniel Goh, Doris Fok, E Shyong Tai, Elaine Tham, Elaine Quah Phaik Ling, Evelyn Chung Ning Law, Evelyn Xiu Ling Loo, Falk Mueller-Riemenschneider, George Seow Heong Yeo, Helen Chen, Heng Hao Tan, Hugo P S van Bever, Iliana Magiati, Inez Bik Yun Wong, Ivy Yee-Man Lau, Jeevesh Kapur, Jenny L. Richmond, Jerry Kok Yen Chan, Joanna D. Holbrook, Joanne Yoong, Joao N. Ferreira., Jonathan Y. Bernard, Joshua J. Gooley, Kenneth Kwek, Krishnamoorthy Niduvaje, Kuan Jin Lee, Leher Singh, Lin Lin Su, Lourdes Mary Daniel, Mark Hanson, Mary Rauff, Mei Chien Chua, Melvin Khee-Shing Leow, Michael Meaney, Ngee Lek, Oon Hoe Teoh, P. C. Wong, Paulin Tay Straughan, Pratibha Agarwal, Queenie Ling Jun Li, Rob M. van Dam, Salome A. Rebello, Seang-Mei Saw, See Ling Loy, Seng Bin Ang, Shang Chee Chong, Sharon Ng, Shirong Cai, Shu-E Soh, Sok Bee Lim, Stella Tsotsi, Chin-Ying Stephen Hsu, Sue Anne Toh, Swee Chye Quek, Victor Samuel Rajadurai, Walter Stunkel, Wayne Cutfield, Wee Meng Han, and Yin Bun Cheung.

Funding

This work was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore [NMRC/TCR/004-NUS/2008, NMRC/TCR/012-NUHS/2014]. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research [NIHR Senior Investigator (NF-SI-0515-10042), NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20004)], the European Union (Erasmus + Programme Early Nutrition eAcademy Southeast Asia-573651-EPP-1-2016-1-DE-EPPKA2-CBHE-JP and ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation (RG/15/17/3174).

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Correspondence to Yung Seng Lee or Navin Michael.

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YSC, KMG, and SYC are part of an academic consortium that has received research funding from companies selling nutritional products. KMG and SYC have received reimbursement for speaking at conferences sponsored by companies selling nutritional products. All other authors have nothing to disclose.

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Written informed consent and approval from the National Healthcare Group Domain Specific Review Board and SingHealth Centralized Institutional Review Board were obtained (Ethics approval number: NHG DSRB Ref: 2009/00021). The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Ong, Y.Y., Pang, W.W., Huang, J.Y. et al. Breastfeeding may benefit cardiometabolic health of children exposed to increased gestational glycemia in utero. Eur J Nutr 61, 2383–2395 (2022). https://doi.org/10.1007/s00394-022-02800-7

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