Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study

doi:10.1186/s12916-024-03419-7

. 2024 May 20;22(1):203.

doi: 10.1186/s12916-024-03419-7.

Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study

Yiyuan Zhang^{1

2

3

4

5

6

7

8

9}, Kexin Dai^{1

2

3

4

5

6

7

8

9}, Xiaojing Chen^{1

2

3

4

5

6

7

8

9}, Linlin Cui^{10

11

12

13

14

15

16

17

18}, Zi-Jiang Chen^{1

3

4

5

6

7

8

9

19

20}

Affiliations

¹ Institute of Women, Children and Reproductive Health, Cheeloo College of Medicine, Shandong University, Shandong, 250012, China.
² Institute of Women, Children and Reproductive Health, the Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong, 250012, China.
³ State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, 250012, China.
⁴ National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.
⁵ Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.
⁶ Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.
⁷ Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.
⁸ Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250012, China.
⁹ Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China.
¹⁰ Institute of Women, Children and Reproductive Health, the Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong, 250012, China. liy@sdu.edu.cn.
¹¹ State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹² National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹³ Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁴ Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁵ Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁶ Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250012, China. liy@sdu.edu.cn.
¹⁷ Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁸ , Jinan, China. liy@sdu.edu.cn.
¹⁹ Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁰ Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.

PMID: 38764021
PMCID: PMC11104001
DOI: 10.1186/s12916-024-03419-7

Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study

Yiyuan Zhang et al. BMC Med. 2024.

. 2024 May 20;22(1):203.

doi: 10.1186/s12916-024-03419-7.

Authors

Affiliations

¹ Institute of Women, Children and Reproductive Health, Cheeloo College of Medicine, Shandong University, Shandong, 250012, China.
² Institute of Women, Children and Reproductive Health, the Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong, 250012, China.
³ State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, 250012, China.
⁴ National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.
⁵ Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.
⁶ Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.
⁷ Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.
⁸ Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250012, China.
⁹ Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China.
¹⁰ Institute of Women, Children and Reproductive Health, the Second Hospital, Cheeloo College of Medicine, Shandong University, Shandong, 250012, China. liy@sdu.edu.cn.
¹¹ State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹² National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹³ Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁴ Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁵ Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁶ Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250012, China. liy@sdu.edu.cn.
¹⁷ Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. liy@sdu.edu.cn.
¹⁸ , Jinan, China. liy@sdu.edu.cn.
¹⁹ Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁰ Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.

PMID: 38764021
PMCID: PMC11104001
DOI: 10.1186/s12916-024-03419-7

Abstract

Background: To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children.

Methods: This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI).

Results: 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m² and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty.

Conclusions: Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty.

Keywords: Assisted reproductive technology; Cardiovascular metabolic health; Large for gestational age; Obesity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Cited by

Associations Between Birth Characteristics, Weaning Practices, and the Metabolic Syndrome in Children: A Descriptive Study.
Bizerea-Moga TO, Moga TV, Stroescu R, Chisavu L, Mărginean O, Chisavu F. Bizerea-Moga TO, et al. Metabolites. 2025 Feb 22;15(3):148. doi: 10.3390/metabo15030148. Metabolites. 2025. PMID: 40137113 Free PMC article.

References

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[1] Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–781. doi: 10.1016/S0140-6736(14)60460-8. - DOI - PMC - PubMed

[2] Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–781. doi: 10.1016/S0140-6736(14)60460-8. - DOI - PMC - PubMed

[3] Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi-Lakeh M, Naghavi M, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13–27. doi: 10.1056/NEJMoa1614362. - DOI - PMC - PubMed

[4] Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi-Lakeh M, Naghavi M, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13–27. doi: 10.1056/NEJMoa1614362. - DOI - PMC - PubMed

[5] Haslam DW, James WP. Obesity. Lancet. 2005;366(9492):1197–1209. doi: 10.1016/S0140-6736(05)67483-1. - DOI - PubMed

[6] Haslam DW, James WP. Obesity. Lancet. 2005;366(9492):1197–1209. doi: 10.1016/S0140-6736(05)67483-1. - DOI - PubMed

[7] Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008;9(5):474–488. doi: 10.1111/j.1467-789X.2008.00475.x. - DOI - PubMed

[8] Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008;9(5):474–488. doi: 10.1111/j.1467-789X.2008.00475.x. - DOI - PubMed

[9] Mahoney LT, Burns TL, Stanford W, Thompson BH, Witt JD, Rost CA, Lauer RM. Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol. 1996;27(2):277–284. doi: 10.1016/0735-1097(95)00461-0. - DOI - PubMed

[10] Mahoney LT, Burns TL, Stanford W, Thompson BH, Witt JD, Rost CA, Lauer RM. Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol. 1996;27(2):277–284. doi: 10.1016/0735-1097(95)00461-0. - DOI - PubMed

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Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study

Affiliations

Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

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