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Published in: BMC Medicine 1/2018

Open Access 01-12-2018 | Research article

The growth of assisted reproductive treatment-conceived children from birth to 5 years: a national cohort study

Authors: Mark Hann, Stephen A. Roberts, Stephen W. D’Souza, Peter Clayton, Nick Macklon, Daniel R. Brison

Published in: BMC Medicine | Issue 1/2018

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Abstract

Background

Birth weight and early child growth are important predictors of long-term cardiometabolic disease risk, in line with the Developmental Origins of Health and Disease hypothesis. As human assisted reproductive technologies (ARTs) occur during the sensitive periconceptional window of development, it has recently become a matter of urgency to investigate risk in ART-conceived children.

Methods

We have conducted the first large-scale, national cohort study of early growth in ART children from birth to school age, linking the register of ART, held by the UK’s Human Fertilisation and Embryology Authority, to Scottish maternity and child health databases.

Results

In this study of 5200 ART and 20,800 naturally conceived (NC) control children, linear regression analysis revealed the birthweight of babies born from fresh embryo transfer cycles is 93.7 g [95% CI (76.6, 110.6)g] less than NC controls, whereas babies born from frozen embryo transfer (FET) cycles are 57.5 g [95% CI (30.7, 86.5)g] heavier. Fresh ART babies grew faster from birth (by 7.2 g/week) but remained lighter (by 171 g), at 6–8 weeks, than NC babies and 133 g smaller than FET babies; FET and NC babies were similar. Length and occipital-frontal circumference followed the same pattern. By school entry (4–7 years), weight, length and BMI in boys and girls conceived by fresh ART and FET were similar to those in NC children.

Conclusions

ART babies born from fresh embryo transfer grow more slowly in utero and in the first few weeks of life, but then show postnatal catch up growth by school age, compared to NC and FET babies. As low birth weight and postnatal catch-up are independent risk factors for cardiometabolic disease over the life-course, we suggest that further studies in this area are now warranted.
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Literature
1.
go back to reference Kupka MS, Ferraretti AP, de Mouzon J, et al. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014;29(10):2099–113.CrossRef Kupka MS, Ferraretti AP, de Mouzon J, et al. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHREdagger. Hum Reprod. 2014;29(10):2099–113.CrossRef
2.
go back to reference Helmerhorst FM, Perquin DA, Donker D, Keirse MJ. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. Bmj. 2004;328(7434):261.CrossRef Helmerhorst FM, Perquin DA, Donker D, Keirse MJ. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. Bmj. 2004;328(7434):261.CrossRef
3.
go back to reference Kamphuis EI, Bhattacharya S, van der Veen F, Mol BW, Templeton A. Evidence Based IVFG. Are we overusing IVF? BMJ. 2014;348:g252.CrossRef Kamphuis EI, Bhattacharya S, van der Veen F, Mol BW, Templeton A. Evidence Based IVFG. Are we overusing IVF? BMJ. 2014;348:g252.CrossRef
4.
go back to reference Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med. 2002;346(10):731–7.CrossRef Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med. 2002;346(10):731–7.CrossRef
5.
go back to reference Sunde A, Brison D, Dumoulin J, et al. Time to take human embryo culture seriously. Hum Reprod. 2016;31(10):2174–82.CrossRef Sunde A, Brison D, Dumoulin J, et al. Time to take human embryo culture seriously. Hum Reprod. 2016;31(10):2174–82.CrossRef
6.
go back to reference Barker DJ. Intrauterine programming of adult disease. Mol Med Today. 1995;1(9):418–23.CrossRef Barker DJ. Intrauterine programming of adult disease. Mol Med Today. 1995;1(9):418–23.CrossRef
7.
go back to reference Roseboom TJ, Painter RC, van Abeelen AF, Veenendaal MV, de Rooij SR. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas. 2011;70(2):141–5.CrossRef Roseboom TJ, Painter RC, van Abeelen AF, Veenendaal MV, de Rooij SR. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas. 2011;70(2):141–5.CrossRef
8.
go back to reference Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000;127(19):4195–202.PubMed Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000;127(19):4195–202.PubMed
9.
go back to reference Vrooman LA, Bartolomei MS. Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse. Reprod Toxicol. 2017;68:72–84.CrossRef Vrooman LA, Bartolomei MS. Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse. Reprod Toxicol. 2017;68:72–84.CrossRef
10.
go back to reference Martin A, Connelly A, Bland RM, Reilly JJ. Health impact of catch-up growth in low-birth weight infants: systematic review, evidence appraisal, and meta-analysis. Matern Child Nutr. 2017;13(1). Martin A, Connelly A, Bland RM, Reilly JJ. Health impact of catch-up growth in low-birth weight infants: systematic review, evidence appraisal, and meta-analysis. Matern Child Nutr. 2017;13(1).
11.
go back to reference Kerkhof GF, Hokken-Koelega AC. Rate of neonatal weight gain and effects on adult metabolic health. Nat Rev Endocrinol. 2012;8(11):689–92.CrossRef Kerkhof GF, Hokken-Koelega AC. Rate of neonatal weight gain and effects on adult metabolic health. Nat Rev Endocrinol. 2012;8(11):689–92.CrossRef
12.
go back to reference Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment: part I--general health outcomes. Hum Reprod Update. 2013;19(3):232–43.CrossRef Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment: part I--general health outcomes. Hum Reprod Update. 2013;19(3):232–43.CrossRef
13.
go back to reference Ceelen M, van Weissenbruch MM, Prein J, et al. Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents. Hum Reprod. 2009;24(11):2788–95.CrossRef Ceelen M, van Weissenbruch MM, Prein J, et al. Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents. Hum Reprod. 2009;24(11):2788–95.CrossRef
14.
go back to reference Maheshwari A, Pandey S, Amalraj Raja E, Shetty A, Hamilton M, Bhattacharya S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update. 2018;24(1):35–58.CrossRef Maheshwari A, Pandey S, Amalraj Raja E, Shetty A, Hamilton M, Bhattacharya S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update. 2018;24(1):35–58.CrossRef
15.
go back to reference Kleijkers SH, Mantikou E, Slappendel E, et al. Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT. Hum Reprod. 2016;31(10):2219–30.CrossRef Kleijkers SH, Mantikou E, Slappendel E, et al. Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT. Hum Reprod. 2016;31(10):2219–30.CrossRef
16.
go back to reference Chen ZJ, Shi Y, Sun Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523–33.CrossRef Chen ZJ, Shi Y, Sun Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523–33.CrossRef
17.
go back to reference Belva F, Henriet S, Van den Abbeel E, et al. Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles. Hum Reprod. 2008;23(10):2227–38.CrossRef Belva F, Henriet S, Van den Abbeel E, et al. Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles. Hum Reprod. 2008;23(10):2227–38.CrossRef
18.
go back to reference Williams CL, Bunch KJ, Stiller CA, et al. Cancer risk among children born after assisted conception. N Engl J Med. 2013;369(19):1819–27.CrossRef Williams CL, Bunch KJ, Stiller CA, et al. Cancer risk among children born after assisted conception. N Engl J Med. 2013;369(19):1819–27.CrossRef
21.
go back to reference Cole TJ. The development of growth references and growth charts. Ann Hum Biol. 2012;39(5):382–94.CrossRef Cole TJ. The development of growth references and growth charts. Ann Hum Biol. 2012;39(5):382–94.CrossRef
22.
go back to reference Wennerholm UB, Henningsen AK, Romundstad LB, et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod. 2013;28(9):2545–53.CrossRef Wennerholm UB, Henningsen AK, Romundstad LB, et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod. 2013;28(9):2545–53.CrossRef
23.
go back to reference Nakashima A, Araki R, Tani H, et al. Implications of assisted reproductive technologies on term singleton birth weight: an analysis of 25,777 children in the national assisted reproduction registry of Japan. Fertil Steril. 2013;99(2):450–5.CrossRef Nakashima A, Araki R, Tani H, et al. Implications of assisted reproductive technologies on term singleton birth weight: an analysis of 25,777 children in the national assisted reproduction registry of Japan. Fertil Steril. 2013;99(2):450–5.CrossRef
24.
go back to reference Lee SH, Lee MY, Chiang TL, Lee MS, Lee MC. Child growth from birth to 18 months old born after assisted reproductive technology--results of a national birth cohort study. Int J Nurs Stud. 2010;47(9):1159–66.CrossRef Lee SH, Lee MY, Chiang TL, Lee MS, Lee MC. Child growth from birth to 18 months old born after assisted reproductive technology--results of a national birth cohort study. Int J Nurs Stud. 2010;47(9):1159–66.CrossRef
25.
go back to reference Yeung EH, Sundaram R, Bell EM, et al. Infertility treatment and children's longitudinal growth between birth and 3 years of age. Hum Reprod. 2016;31(7):1621–8.CrossRef Yeung EH, Sundaram R, Bell EM, et al. Infertility treatment and children's longitudinal growth between birth and 3 years of age. Hum Reprod. 2016;31(7):1621–8.CrossRef
26.
go back to reference Woldringh GH, Hendriks JC, van Klingeren J, et al. Weight of in vitro fertilization and intracytoplasmic sperm injection singletons in early childhood. Fertil Steril. 2011;95(8):2775–7.CrossRef Woldringh GH, Hendriks JC, van Klingeren J, et al. Weight of in vitro fertilization and intracytoplasmic sperm injection singletons in early childhood. Fertil Steril. 2011;95(8):2775–7.CrossRef
27.
go back to reference Basatemur E, Shevlin M, Sutcliffe A. Growth of children conceived by IVF and ICSI up to 12 years of age. Reprod BioMed Online. 2010;20(1):144–9.CrossRef Basatemur E, Shevlin M, Sutcliffe A. Growth of children conceived by IVF and ICSI up to 12 years of age. Reprod BioMed Online. 2010;20(1):144–9.CrossRef
28.
go back to reference Sutcliffe AG, Melhuish E, Barnes J, Gardiner J. Health and development of children born after assisted reproductive technology and sub-fertility compared to naturally conceived children: data from a national study. Pediatr Rep. 2014;6(1):5118.CrossRef Sutcliffe AG, Melhuish E, Barnes J, Gardiner J. Health and development of children born after assisted reproductive technology and sub-fertility compared to naturally conceived children: data from a national study. Pediatr Rep. 2014;6(1):5118.CrossRef
29.
go back to reference Green MP, Mouat F, Miles HL, et al. Phenotypic differences in children conceived from fresh and thawed embryos in in vitro fertilization compared with naturally conceived children. Fertil Steril. 2013;99(7):1898–904.CrossRef Green MP, Mouat F, Miles HL, et al. Phenotypic differences in children conceived from fresh and thawed embryos in in vitro fertilization compared with naturally conceived children. Fertil Steril. 2013;99(7):1898–904.CrossRef
30.
go back to reference Miles HL, Hofman PL, Peek J, et al. In vitro fertilization improves childhood growth and metabolism. J Clin Endocrinol Metab. 2007;92(9):3441–5.CrossRef Miles HL, Hofman PL, Peek J, et al. In vitro fertilization improves childhood growth and metabolism. J Clin Endocrinol Metab. 2007;92(9):3441–5.CrossRef
31.
go back to reference Belfort MB, Rifas-Shiman SL, Rich-Edwards J, Kleinman KP, Gillman MW. Size at birth, infant growth, and blood pressure at three years of age. J Pediatr. 2007;151(6):670–4.CrossRef Belfort MB, Rifas-Shiman SL, Rich-Edwards J, Kleinman KP, Gillman MW. Size at birth, infant growth, and blood pressure at three years of age. J Pediatr. 2007;151(6):670–4.CrossRef
32.
go back to reference Fleming TP, Watkins AJ, Velazquez MA, et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet. 2018;391(10132):1842–52.CrossRef Fleming TP, Watkins AJ, Velazquez MA, et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet. 2018;391(10132):1842–52.CrossRef
33.
go back to reference Fabricius-Bjerre S, Jensen RB, Faerch K, et al. Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence. PLoS One. 2011;6(6):e20595.CrossRef Fabricius-Bjerre S, Jensen RB, Faerch K, et al. Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence. PLoS One. 2011;6(6):e20595.CrossRef
34.
go back to reference Sheng X, Tong M, Zhao D, et al. Randomized controlled trial to compare growth parameters and nutrient adequacy in children with picky eating behaviors who received nutritional counseling with or without an oral nutritional supplement. Nutr Metab Insights. 2014;7:85–94.CrossRef Sheng X, Tong M, Zhao D, et al. Randomized controlled trial to compare growth parameters and nutrient adequacy in children with picky eating behaviors who received nutritional counseling with or without an oral nutritional supplement. Nutr Metab Insights. 2014;7:85–94.CrossRef
35.
go back to reference Sibley C, D'Souza S, Glazier J, Greenwood S. Mechanisms of solute transfer across the human placenta: effects of intrauterine growth restriction. Fetal Matern Med Rev. 1998;10(4):197–206.CrossRef Sibley C, D'Souza S, Glazier J, Greenwood S. Mechanisms of solute transfer across the human placenta: effects of intrauterine growth restriction. Fetal Matern Med Rev. 1998;10(4):197–206.CrossRef
Metadata
Title
The growth of assisted reproductive treatment-conceived children from birth to 5 years: a national cohort study
Authors
Mark Hann
Stephen A. Roberts
Stephen W. D’Souza
Peter Clayton
Nick Macklon
Daniel R. Brison
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2018
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-018-1203-7

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