Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults:  a parental negative control study

Kushala W M Abeysekera; James Orr; Paul C Madley-Dowd; Gwen Sascha Fernandes; Luisa Zuccolo; Fiona H Gordon; Debbie A Lawlor; Jon E Heron; Matt  Hickman

doi:10.1016/j.lanepe.2021.100206

Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study

Kushala W M Abeysekera^*, James Orr, Paul C Madley-Dowd, Gwen Sascha Fernandes, Luisa Zuccolo, Fiona H Gordon, Debbie A Lawlor, Jon E Heron, Matt Hickman

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Background
The importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.

Methods
4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch®. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI.

Findings
There was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74].

Interpretation
Higher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD.

Funding
Medical Research Council UK, Alcohol Research UK, David Telling Charitable Trust

Keywords
ALSPACNon-alcoholic fatty liver diseaseYoung adultsTransient elastographyControlled attenuation parameterBreastfeedingMaternal pre-pregnancy BMI

Original language	English
Article number	100206
Journal	The Lancet Regional Health - Europe
Volume	10
Early online date	5 Sep 2021
DOIs	https://doi.org/10.1016/j.lanepe.2021.100206
Publication status	Published - Nov 2021

Bibliographical note

Funding Information:
The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This work was undertaken with the support of the MRC and Alcohol Research UK (MR/L022206/1), and the David Telling Charitable Trust. We also acknowledge support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer), a UKCRC Public Health Research Centre of Excellence (joint funding (MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, the NIHR School of Public Health Research, NIHR Health Protection Research Unit in Behavioural Science and Evaluation and NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust. LZ, DAL and HM work in a unit that receive funds from the University of Bristol and Medical Research Council (MC_UU_00011/6) and DAL's contribution to this paper is also supported by the Bristol NIHR Biomedical Research Centre. DAL (NF-0616-10102) and MH (G123511-101) are NIHR Senior Investigators. None of the funders influenced the research question, analysis plan or interpretation of results. The views expressed in this paper are those of the authors and not necessarily any listed funders.

Publisher Copyright:
© 2021

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8073 MRC IEU - Programme 6
Lawlor, D. A.
1/04/18 → 31/03/23
Project: Research

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@article{f39ec0cfe6a7470cbe21eb7c60cf35cb,

title = "Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study",

abstract = "BackgroundThe importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.Methods4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch{\textregistered}. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI.FindingsThere was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74].InterpretationHigher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD.FundingMedical Research Council UK, Alcohol Research UK, David Telling Charitable TrustKeywordsALSPACNon-alcoholic fatty liver diseaseYoung adultsTransient elastographyControlled attenuation parameterBreastfeedingMaternal pre-pregnancy BMI",

author = "Abeysekera, {Kushala W M} and James Orr and Madley-Dowd, {Paul C} and Fernandes, {Gwen Sascha} and Luisa Zuccolo and Gordon, {Fiona H} and Lawlor, {Debbie A} and Heron, {Jon E} and Matt Hickman",

note = "Funding Information: The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This work was undertaken with the support of the MRC and Alcohol Research UK (MR/L022206/1), and the David Telling Charitable Trust. We also acknowledge support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer), a UKCRC Public Health Research Centre of Excellence (joint funding (MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, the NIHR School of Public Health Research, NIHR Health Protection Research Unit in Behavioural Science and Evaluation and NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust. LZ, DAL and HM work in a unit that receive funds from the University of Bristol and Medical Research Council (MC_UU_00011/6) and DAL's contribution to this paper is also supported by the Bristol NIHR Biomedical Research Centre. DAL (NF-0616-10102) and MH (G123511-101) are NIHR Senior Investigators. None of the funders influenced the research question, analysis plan or interpretation of results. The views expressed in this paper are those of the authors and not necessarily any listed funders. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = nov,

doi = "10.1016/j.lanepe.2021.100206",

language = "English",

volume = "10",

journal = "The Lancet Regional Health - Europe",

issn = "2666-7762",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults

T2 - a parental negative control study

AU - Abeysekera, Kushala W M

AU - Orr, James

AU - Madley-Dowd, Paul C

AU - Fernandes, Gwen Sascha

AU - Zuccolo, Luisa

AU - Gordon, Fiona H

AU - Lawlor, Debbie A

AU - Heron, Jon E

AU - Hickman, Matt

N1 - Funding Information: The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This work was undertaken with the support of the MRC and Alcohol Research UK (MR/L022206/1), and the David Telling Charitable Trust. We also acknowledge support from The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer), a UKCRC Public Health Research Centre of Excellence (joint funding (MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, the NIHR School of Public Health Research, NIHR Health Protection Research Unit in Behavioural Science and Evaluation and NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust. LZ, DAL and HM work in a unit that receive funds from the University of Bristol and Medical Research Council (MC_UU_00011/6) and DAL's contribution to this paper is also supported by the Bristol NIHR Biomedical Research Centre. DAL (NF-0616-10102) and MH (G123511-101) are NIHR Senior Investigators. None of the funders influenced the research question, analysis plan or interpretation of results. The views expressed in this paper are those of the authors and not necessarily any listed funders. Publisher Copyright: © 2021

PY - 2021/11

Y1 - 2021/11

N2 - BackgroundThe importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.Methods4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch®. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI.FindingsThere was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74].InterpretationHigher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD.FundingMedical Research Council UK, Alcohol Research UK, David Telling Charitable TrustKeywordsALSPACNon-alcoholic fatty liver diseaseYoung adultsTransient elastographyControlled attenuation parameterBreastfeedingMaternal pre-pregnancy BMI

AB - BackgroundThe importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.Methods4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch®. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI.FindingsThere was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74].InterpretationHigher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD.FundingMedical Research Council UK, Alcohol Research UK, David Telling Charitable TrustKeywordsALSPACNon-alcoholic fatty liver diseaseYoung adultsTransient elastographyControlled attenuation parameterBreastfeedingMaternal pre-pregnancy BMI

U2 - 10.1016/j.lanepe.2021.100206

DO - 10.1016/j.lanepe.2021.100206

M3 - Article (Academic Journal)

C2 - 34806068

VL - 10

JO - The Lancet Regional Health - Europe

JF - The Lancet Regional Health - Europe

SN - 2666-7762

M1 - 100206

ER -

Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study

Abstract

Bibliographical note

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Projects

8073 MRC IEU - Programme 6

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