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Long-chain polyunsaturated fatty acids, gestation duration and birth size: a Mendelian randomization study using FADS variants

Long-chain polyunsaturated fatty acids, gestation duration and birth size: a Mendelian randomization study using FADS variants
Long-chain polyunsaturated fatty acids, gestation duration and birth size: a Mendelian randomization study using FADS variants
Background
In randomized trials, supplementation of n–3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy has resulted in increased size at birth, which is attributable to longer gestation.
Objective
We examined this finding by using a Mendelian randomization approach utilizing fatty acid desaturase (FADS) gene variants affecting LC-PUFA metabolism.
Design
As part of a tri-ethnic mother-offspring cohort in Singapore, 35 genetic variants in FADS1, FADS2, and FADS3 were genotyped in 898 mothers and 1103 offspring. Maternal plasma n–3 and n–6 PUFA concentrations at 26–28 wk of gestation were measured. Gestation duration was derived from an ultrasound dating scan in early pregnancy and from birth date. Birth length and weight were measured. Eight FADS variants were selected through a tagging-SNP approach and examined in association with PUFA concentrations, gestation duration among spontaneous labors, and birth size with the use of ethnicity-adjusted linear regressions and survival models that accounted for the competing risks of induced labor and prelabor cesarean delivery.
Results
Maternal FADS1 variant rs174546, tagging for 8 other variants located on FADS1 and FADS2, was strongly related to plasma n–6 but not n–3 LC-PUFA concentrations. Offspring and maternal FADS3 variants were associated with gestation duration among women who had spontaneous labor: each copy of rs174450 minor allele C was associated with a shorter gestation by 2.2 d (95% CI: 0.9, 3.4 d) and 1.9 d (0.7, 3.0 d) for maternal and offspring variants, respectively. In survival models, rs174450 minor allele homozygotes had reduced time to delivery after spontaneous labor compared with major allele homozygotes [HR (95% CI): 1.51 (1.18, 1.95) and 1.51 (1.20, 1.89) for mothers and offspring, respectively].
Conclusions
With the use of a Mendelian randomization approach, we observed associations between FADS variants and gestation duration. This suggests a potential role of LC-PUFAs in gestation duration. This trial was registered at http://www.clinicaltrials.gov as NCT01174875.
0002-9165
92-100
Bernard, Jonathan Y.
c831fc27-9e1a-46ca-b335-859e14c5083b
Pan, Hong
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Aris, Izzuddin M.
ee15a46e-ead3-4b4a-a208-d39038a85480
Moreno-Betancur, Margarita
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Soh, Shu-E
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Yap, Fabian
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Tan, Kok Hian
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Shek, Lynette P.
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Chong, Yap-Seng
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Gluckman, Peter D.
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Calder, Philip C.
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Godfrey, Keith M.
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Chong, Mary F.F.
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Kramer, Michael S.
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Karnani, Neerja
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Lee, Yung Seng
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Bernard, Jonathan Y.
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Pan, Hong
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Aris, Izzuddin M.
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Moreno-Betancur, Margarita
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Soh, Shu-E
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Yap, Fabian
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Tan, Kok Hian
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Shek, Lynette P.
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Chong, Yap-Seng
7043124b-e892-4d4b-8bb7-6d35ed94e136
Gluckman, Peter D.
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Calder, Philip C.
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Godfrey, Keith M.
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Chong, Mary F.F.
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Kramer, Michael S.
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Karnani, Neerja
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Lee, Yung Seng
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Bernard, Jonathan Y., Pan, Hong, Aris, Izzuddin M., Moreno-Betancur, Margarita, Soh, Shu-E, Yap, Fabian, Tan, Kok Hian, Shek, Lynette P., Chong, Yap-Seng, Gluckman, Peter D., Calder, Philip C., Godfrey, Keith M., Chong, Mary F.F., Kramer, Michael S., Karnani, Neerja and Lee, Yung Seng (2018) Long-chain polyunsaturated fatty acids, gestation duration and birth size: a Mendelian randomization study using FADS variants. American Journal of Clinical Nutrition, 108 (1), 92-100. (doi:10.1093/ajcn/nqy079).

Record type: Article

Abstract

Background
In randomized trials, supplementation of n–3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy has resulted in increased size at birth, which is attributable to longer gestation.
Objective
We examined this finding by using a Mendelian randomization approach utilizing fatty acid desaturase (FADS) gene variants affecting LC-PUFA metabolism.
Design
As part of a tri-ethnic mother-offspring cohort in Singapore, 35 genetic variants in FADS1, FADS2, and FADS3 were genotyped in 898 mothers and 1103 offspring. Maternal plasma n–3 and n–6 PUFA concentrations at 26–28 wk of gestation were measured. Gestation duration was derived from an ultrasound dating scan in early pregnancy and from birth date. Birth length and weight were measured. Eight FADS variants were selected through a tagging-SNP approach and examined in association with PUFA concentrations, gestation duration among spontaneous labors, and birth size with the use of ethnicity-adjusted linear regressions and survival models that accounted for the competing risks of induced labor and prelabor cesarean delivery.
Results
Maternal FADS1 variant rs174546, tagging for 8 other variants located on FADS1 and FADS2, was strongly related to plasma n–6 but not n–3 LC-PUFA concentrations. Offspring and maternal FADS3 variants were associated with gestation duration among women who had spontaneous labor: each copy of rs174450 minor allele C was associated with a shorter gestation by 2.2 d (95% CI: 0.9, 3.4 d) and 1.9 d (0.7, 3.0 d) for maternal and offspring variants, respectively. In survival models, rs174450 minor allele homozygotes had reduced time to delivery after spontaneous labor compared with major allele homozygotes [HR (95% CI): 1.51 (1.18, 1.95) and 1.51 (1.20, 1.89) for mothers and offspring, respectively].
Conclusions
With the use of a Mendelian randomization approach, we observed associations between FADS variants and gestation duration. This suggests a potential role of LC-PUFAs in gestation duration. This trial was registered at http://www.clinicaltrials.gov as NCT01174875.

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1. Manuscript_v10_and_Tables_FADS_and_GA - Accepted Manuscript
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More information

Accepted/In Press date: 23 March 2018
e-pub ahead of print date: 6 June 2018
Published date: 1 July 2018

Identifiers

Local EPrints ID: 419295
URI: http://eprints.soton.ac.uk/id/eprint/419295
ISSN: 0002-9165
PURE UUID: b7c67aa3-c2c5-4e81-abc1-3112e8f87433
ORCID for Philip C. Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

Catalogue record

Date deposited: 10 Apr 2018 16:30
Last modified: 26 Nov 2021 06:26

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Contributors

Author: Jonathan Y. Bernard
Author: Hong Pan
Author: Izzuddin M. Aris
Author: Margarita Moreno-Betancur
Author: Shu-E Soh
Author: Fabian Yap
Author: Kok Hian Tan
Author: Lynette P. Shek
Author: Yap-Seng Chong
Author: Peter D. Gluckman
Author: Mary F.F. Chong
Author: Michael S. Kramer
Author: Neerja Karnani
Author: Yung Seng Lee

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