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Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage

BACKGROUND: In infancy, males are at higher risk of dying than females. Birthweight and gestational age are potential confounders or mediators but are also familial and correlated, posing epidemiological challenges that can be addressed by studying male-female twin pairs. METHODS: We studied 28 558...

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Autores principales: Calais-Ferreira, Lucas, Barreto, Marcos E, Mendonça, Everton, Dite, Gillian S, Hickey, Martha, Ferreira, Paulo H, Scurrah, Katrina J, Hopper, John L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9557851/
https://www.ncbi.nlm.nih.gov/pubmed/34849953
http://dx.doi.org/10.1093/ije/dyab242
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author Calais-Ferreira, Lucas
Barreto, Marcos E
Mendonça, Everton
Dite, Gillian S
Hickey, Martha
Ferreira, Paulo H
Scurrah, Katrina J
Hopper, John L
author_facet Calais-Ferreira, Lucas
Barreto, Marcos E
Mendonça, Everton
Dite, Gillian S
Hickey, Martha
Ferreira, Paulo H
Scurrah, Katrina J
Hopper, John L
author_sort Calais-Ferreira, Lucas
collection PubMed
description BACKGROUND: In infancy, males are at higher risk of dying than females. Birthweight and gestational age are potential confounders or mediators but are also familial and correlated, posing epidemiological challenges that can be addressed by studying male-female twin pairs. METHODS: We studied 28 558 male-female twin pairs born in Brazil between 2012 and 2016, by linking their birth and death records. Using a co-twin control study matched for gestational age and familial factors, we applied logistic regression with random effects (to account for paired data) to study the association between male sex and infant death, adjusting for: birthweight, within- and between-pair effects of birthweight, birth order and gestational age, including interactions. The main outcome was infant mortality (0–365 days) stratified by neonatal (early and late) and postneonatal deaths. RESULTS: Males were 100 g heavier and more at risk of infant death than their female co-twins before [odds ratio (OR)  = 1.28, 95% confidence interval (CI): 1.11–1.49, P = 0.001] and after (OR = 1.60, 95% CI: 1.39–1.83, P <0.001) adjusting for birthweight and birth order. When adjusting for birthweight within-pair difference and mean separately, the OR attenuated to 1.40 (95% CI: 1.21–1.61, P <0.001), with evidence of familial confounding (likelihood ratio test, P <0.001). We found evidence of interaction (P = 0.001) between male sex and gestational age for early neonatal death. CONCLUSIONS: After matching for gestational age and familial factors by design and controlling for birthweight and birth order, males remain at greater risk of infant death than their female co-twins. Birthweight’s role as a confounder can be partially explained by familial factors.
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spelling pubmed-95578512022-10-14 Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage Calais-Ferreira, Lucas Barreto, Marcos E Mendonça, Everton Dite, Gillian S Hickey, Martha Ferreira, Paulo H Scurrah, Katrina J Hopper, John L Int J Epidemiol Perinatal and Infant Health BACKGROUND: In infancy, males are at higher risk of dying than females. Birthweight and gestational age are potential confounders or mediators but are also familial and correlated, posing epidemiological challenges that can be addressed by studying male-female twin pairs. METHODS: We studied 28 558 male-female twin pairs born in Brazil between 2012 and 2016, by linking their birth and death records. Using a co-twin control study matched for gestational age and familial factors, we applied logistic regression with random effects (to account for paired data) to study the association between male sex and infant death, adjusting for: birthweight, within- and between-pair effects of birthweight, birth order and gestational age, including interactions. The main outcome was infant mortality (0–365 days) stratified by neonatal (early and late) and postneonatal deaths. RESULTS: Males were 100 g heavier and more at risk of infant death than their female co-twins before [odds ratio (OR)  = 1.28, 95% confidence interval (CI): 1.11–1.49, P = 0.001] and after (OR = 1.60, 95% CI: 1.39–1.83, P <0.001) adjusting for birthweight and birth order. When adjusting for birthweight within-pair difference and mean separately, the OR attenuated to 1.40 (95% CI: 1.21–1.61, P <0.001), with evidence of familial confounding (likelihood ratio test, P <0.001). We found evidence of interaction (P = 0.001) between male sex and gestational age for early neonatal death. CONCLUSIONS: After matching for gestational age and familial factors by design and controlling for birthweight and birth order, males remain at greater risk of infant death than their female co-twins. Birthweight’s role as a confounder can be partially explained by familial factors. Oxford University Press 2021-11-29 /pmc/articles/PMC9557851/ /pubmed/34849953 http://dx.doi.org/10.1093/ije/dyab242 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Perinatal and Infant Health
Calais-Ferreira, Lucas
Barreto, Marcos E
Mendonça, Everton
Dite, Gillian S
Hickey, Martha
Ferreira, Paulo H
Scurrah, Katrina J
Hopper, John L
Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
title Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
title_full Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
title_fullStr Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
title_full_unstemmed Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
title_short Birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of Brazilian male-female twin pairs identified by population data linkage
title_sort birthweight, gestational age and familial confounding in sex differences in infant mortality: a matched co-twin control study of brazilian male-female twin pairs identified by population data linkage
topic Perinatal and Infant Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9557851/
https://www.ncbi.nlm.nih.gov/pubmed/34849953
http://dx.doi.org/10.1093/ije/dyab242
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