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Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort

STUDY QUESTION: Do twins conceived through assisted reproductive treatments (ART) grow differently from naturally conceived (NC) twins in early life? SUMMARY ANSWER: Assessments at 6–8 weeks old and at school entry show that ART twins conceived from frozen embryo transfer (FET) grow faster than both...

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Autores principales: Kondowe, Fiskani J M, Clayton, Peter, Gittins, Matthew, D’Souza, Stephen W, Brison, Daniel R, Roberts, Stephen A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068277/
https://www.ncbi.nlm.nih.gov/pubmed/36763679
http://dx.doi.org/10.1093/humrep/dead018
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author Kondowe, Fiskani J M
Clayton, Peter
Gittins, Matthew
D’Souza, Stephen W
Brison, Daniel R
Roberts, Stephen A
author_facet Kondowe, Fiskani J M
Clayton, Peter
Gittins, Matthew
D’Souza, Stephen W
Brison, Daniel R
Roberts, Stephen A
author_sort Kondowe, Fiskani J M
collection PubMed
description STUDY QUESTION: Do twins conceived through assisted reproductive treatments (ART) grow differently from naturally conceived (NC) twins in early life? SUMMARY ANSWER: Assessments at 6–8 weeks old and at school entry show that ART twins conceived from frozen embryo transfer (FET) grow faster than both NC twins and ART twins conceived from fresh embryo transfer (ET). WHAT IS KNOWN ALREADY: Singletons born from fresh ET 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. Evidence on early child growth of ART twins relative to NC twins is inconsistent; most studies are small and do not distinguish FET from fresh ET cycles. STUDY DESIGN, SIZE, DURATION: This cohort study included 13 528 live-born twin babies conceived by ART (fresh ET: 2792, FET: 556) and NC (10 180) between 1991 and 2009 in Scotland. The data were obtained by linking Human Fertilisation and Embryology Authority ART register data to the Scottish Morbidity Record (SMR02) and Scottish child health programme datasets. Outcome data were collected at birth, 6–8 weeks (first assessment), and school entry (4–7 years old) assessments. The primary outcome was growth, measured by weight at the three assessment points. Secondary outcomes were length (at birth and 6–8 weeks) or height (at school entry), BMI, occipital circumference, gestational age at birth, newborn intensive care unit admission, and growth rates (between birth and 6–8 weeks and between 6–8 weeks and school entry). PARTICIPANTS/MATERIALS, SETTING, METHODS: All twins in the linked dataset (born between 1991 and 2009) with growth data were included in the analysis. To determine outcome differences between fresh ET, FET, and NC twins, linear mixed models (or analogous logistic regression models) were used to explore the outcomes of interest. All models were adjusted for available confounders: gestational age/child age, gender, maternal age and smoking, Scottish Index of Multiple Deprivation, year of treatment, parity, ICSI, and ET stage. MAIN RESULTS AND THE ROLE OF CHANCE: In the primary birth weight models, the average birth weight of fresh ET twins was lower [–35 g; 95% CI: (−53, −16)g] than NC controls, while FET twins were heavier [71 g; 95% CI (33, 110) g] than NC controls and heavier [106 g; 95% CI (65, 146) g] than fresh ET twins. However, the difference between FET and NC twins was not significant when considering only full-term twins (≥37 weeks gestation) [26 g; 95% CI (–30, 82) g], while it was significantly higher in preterm twins [126 g; 95% CI (73, 179) g]. Growth rates did not differ significantly for the three groups from birth to 6–8 weeks. However, FET twins grew significantly faster from 6 to 8 weeks than NC (by 2.2 g/week) and fresh ET twins (by 2.1 g/week). By school entry, FET twins were 614 g [95% CI (158, 1070) g] and 581 g [95% CI (100, 1063) g] heavier than NC and fresh ET twins, respectively. Length/height and occipital frontal circumference did not differ significantly at any time point. LIMITATIONS, REASONS FOR CAUTION: Although the differences between ART and NC reflect the true ART effects, these effects are likely to be mediated partly through the different prevalence of mono/dizygotic twins in the two groups. We could not explore the mediating effect of zygosity due to the unavailability of data. The confounding variables included in the study were limited to those available in the datasets. WIDER IMPLICATIONS OF THE FINDINGS: Live-born twins from FET cycles are heavier at birth, grow faster than their fresh ET and NC counterparts, and are still heavier at school entry. This differs from that observed in singletons from the same cohort, where babies in the three conception groups had similar weights by school entry age. The results are reassuring on known differences in FET versus fresh ET and NC twin outcomes. However, FET twins grow faster and are consistently larger, and more ART twins depict catch-up growth. These may lead to an increased risk profile for non-communicable diseases in later life. As such, these twin outcomes require careful evaluation using more recent and comprehensive cohorts. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the EU H2020 Marie Sklodowska‐Curie Innovative Training Networks (ITN) grant Dohartnet (H2020‐MSCA‐ITN‐2018-812660). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.
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spelling pubmed-100682772023-04-04 Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort Kondowe, Fiskani J M Clayton, Peter Gittins, Matthew D’Souza, Stephen W Brison, Daniel R Roberts, Stephen A Hum Reprod Original Article STUDY QUESTION: Do twins conceived through assisted reproductive treatments (ART) grow differently from naturally conceived (NC) twins in early life? SUMMARY ANSWER: Assessments at 6–8 weeks old and at school entry show that ART twins conceived from frozen embryo transfer (FET) grow faster than both NC twins and ART twins conceived from fresh embryo transfer (ET). WHAT IS KNOWN ALREADY: Singletons born from fresh ET 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. Evidence on early child growth of ART twins relative to NC twins is inconsistent; most studies are small and do not distinguish FET from fresh ET cycles. STUDY DESIGN, SIZE, DURATION: This cohort study included 13 528 live-born twin babies conceived by ART (fresh ET: 2792, FET: 556) and NC (10 180) between 1991 and 2009 in Scotland. The data were obtained by linking Human Fertilisation and Embryology Authority ART register data to the Scottish Morbidity Record (SMR02) and Scottish child health programme datasets. Outcome data were collected at birth, 6–8 weeks (first assessment), and school entry (4–7 years old) assessments. The primary outcome was growth, measured by weight at the three assessment points. Secondary outcomes were length (at birth and 6–8 weeks) or height (at school entry), BMI, occipital circumference, gestational age at birth, newborn intensive care unit admission, and growth rates (between birth and 6–8 weeks and between 6–8 weeks and school entry). PARTICIPANTS/MATERIALS, SETTING, METHODS: All twins in the linked dataset (born between 1991 and 2009) with growth data were included in the analysis. To determine outcome differences between fresh ET, FET, and NC twins, linear mixed models (or analogous logistic regression models) were used to explore the outcomes of interest. All models were adjusted for available confounders: gestational age/child age, gender, maternal age and smoking, Scottish Index of Multiple Deprivation, year of treatment, parity, ICSI, and ET stage. MAIN RESULTS AND THE ROLE OF CHANCE: In the primary birth weight models, the average birth weight of fresh ET twins was lower [–35 g; 95% CI: (−53, −16)g] than NC controls, while FET twins were heavier [71 g; 95% CI (33, 110) g] than NC controls and heavier [106 g; 95% CI (65, 146) g] than fresh ET twins. However, the difference between FET and NC twins was not significant when considering only full-term twins (≥37 weeks gestation) [26 g; 95% CI (–30, 82) g], while it was significantly higher in preterm twins [126 g; 95% CI (73, 179) g]. Growth rates did not differ significantly for the three groups from birth to 6–8 weeks. However, FET twins grew significantly faster from 6 to 8 weeks than NC (by 2.2 g/week) and fresh ET twins (by 2.1 g/week). By school entry, FET twins were 614 g [95% CI (158, 1070) g] and 581 g [95% CI (100, 1063) g] heavier than NC and fresh ET twins, respectively. Length/height and occipital frontal circumference did not differ significantly at any time point. LIMITATIONS, REASONS FOR CAUTION: Although the differences between ART and NC reflect the true ART effects, these effects are likely to be mediated partly through the different prevalence of mono/dizygotic twins in the two groups. We could not explore the mediating effect of zygosity due to the unavailability of data. The confounding variables included in the study were limited to those available in the datasets. WIDER IMPLICATIONS OF THE FINDINGS: Live-born twins from FET cycles are heavier at birth, grow faster than their fresh ET and NC counterparts, and are still heavier at school entry. This differs from that observed in singletons from the same cohort, where babies in the three conception groups had similar weights by school entry age. The results are reassuring on known differences in FET versus fresh ET and NC twin outcomes. However, FET twins grow faster and are consistently larger, and more ART twins depict catch-up growth. These may lead to an increased risk profile for non-communicable diseases in later life. As such, these twin outcomes require careful evaluation using more recent and comprehensive cohorts. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the EU H2020 Marie Sklodowska‐Curie Innovative Training Networks (ITN) grant Dohartnet (H2020‐MSCA‐ITN‐2018-812660). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A. Oxford University Press 2023-02-10 /pmc/articles/PMC10068277/ /pubmed/36763679 http://dx.doi.org/10.1093/humrep/dead018 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Kondowe, Fiskani J M
Clayton, Peter
Gittins, Matthew
D’Souza, Stephen W
Brison, Daniel R
Roberts, Stephen A
Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
title Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
title_full Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
title_fullStr Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
title_full_unstemmed Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
title_short Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
title_sort growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068277/
https://www.ncbi.nlm.nih.gov/pubmed/36763679
http://dx.doi.org/10.1093/humrep/dead018
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