2 La construcción en altura en la visión marxistade Jaramillo
3.2 Análisis de Componentes Principales (ACP)
3.2.1 Descripción de los datos y ACP
Iris ALM van Rooij, Charlotte HW Wijers, Paul NMA Rieu,
Hester S Hendriks, Marijn M Brouwers, Nine VAM Knoers,
Ivo de Blaauw, Nel Roeleveld
Birth Defects Research Part A: Clinical and Molecular Teratology
2010;88:152-158
Chapter 7
Maternal and paternal risk factors for anorectal
malformations: a Dutch case-control study
Iris ALM van Rooij, Charlotte HW Wijers, Paul NMA Rieu,
Hester S Hendriks, Marijn M Brouwers, Nine VAM Knoers,
Ivo de Blaauw, Nel Roeleveld
Birth Defects Research Part A: Clinical and Molecular Teratology
2010;88:152-158
Abstract
Background Anorectal malformations (ARM) are major congenital malformations that
usually require a multitude of surgical procedures at very early age and have a large impact on the lives of patients and their parents. The causes of ARM are still largerly unknown, but it is assumed to have a multifactorial etiology. A few studies focused on environmental risk factors, but evidence is still scarce.
Methods In this Dutch case-control study (1996-2008), we investigated the role of maternal
and paternal risk factors in the etiology of ARM. Parents of 85 ARM cases and 650 controls filled in a questionnaire. Controls were children treated with ear ventilation tubes.
Results A higher occurrence of fever during the first trimester of pregnancy was found for
case mothers compared to control mothers (odds ratio (OR), 5.1; 95% Confidence Interval (CI), 0.9, 28.1). Maternal occupational exposure to industrial cleaning agents and solvents increased the risk of ARM three times (OR, 2.9; 95% CI, 0.9, 9.3). Overweight (Body Mass Index (BMI) ≥ 25 kg/m2) before pregnancy also seemed to be associated with ARM (OR, 1.8;
95% CI, 1.1, 2.8), as well as maternal multivitamin use during pregnancy (OR, 1.6; 95% CI, 1.0, 2.7), paternal smoking (OR, 1.8; 95% CI, 1.1, 2.9) and paternal occupational exposure to exhaust fumes (OR, 1.9; 95% CI, 1.0, 3.6). Reported ARM in at least one first or second degree family member greatly increased the risk of having a child with ARM (OR, 40.3; 95% CI, 4.8, 342.8).
Conclusions This study revealed potential risk factors for ARM, including fever during
pregnancy, maternal overweight, use of multivitamins, paternal smoking, and occupational exposures, but a familial component seems important as well.
Introduction
Congenital anorectal malformations (ARM) are the most common gastrointestinal anomalies at birth. The worldwide prevalence of ARM is estimated to be 1 in 1500 to 1 in 5000 live births.1 Anorectal anomalies include a wide range of phenotypes depending on location and
size of the defect. They usually require multiple surgical procedures at very early age and have a major impact on the lives of patients and their parents. Additional congenital anomalies are present in approximately 50% of ARM cases, especially anomalies of the heart, kidneys, spine, urogenital tract, and other gastrointestinal atresias, in particular as components of the VACTERL association (Vertebral defects, Anal atresia, Cardiac defects, Tracheo-Esophageal fistula, Renal anomalies, Radial dysplasia, and Limb defects). Not much is known about the etiology of ARM, apart from a few identified genes that have been implicated in syndromes including ARM or were derived from animal studies. Townes-Brocks syndrome, with combinations of anal, renal, limb, and ear anomalies, is caused by mutations in the SALL1 zinc-finger protein.2 Linkage and mutational analyses in patients with the Currarino syndrome, in which sacral malformations are found along with ARM, identified the homeobox gene HLXB9 as a major locus.3 Mutant mice with various defects in the signaling
pathway of sonic hedgehog exhibit a spectrum of distal hindgut defects mimicking human ARM, while mutant mice lacking Gli2 or Gli3 show imperforate anus with recto-urethral fistula and anal stenosis.4,5
Although evidence exists for genetic contribution to ARM based on these studies, nonsyndromic anorectal anomalies rarely aggregate in families.6 This points towards a
substantial role for environmental risk factors. A Japanese study suggested maternal alcohol drinking in early pregnancy as a risk factor for isolated anal atresia,7 that could not be
confirmed by others.8,9 Cigarette smoking and caffeine intake were found to be associated
with anal atresia in the US,9 whereas in France and Spain, associations with medical drug use during pregnancy were found,8 in particular use of the benzodiazepine lorazepam.10 Paternal
exposure to occupational hazards, such as organic solvents and metals in vehicle manufacturers seemed to be associated with anal atresia as well.8,11 Based on a single study
in China, it has been suggested that periconceptional folic acid supplementation may reduce the risk of anal atresia.12 Most of these potential risk factors stem from only one
epidemiologic study per risk factor, which is not sufficient for conclusions about causality. Moreover, none of these studies investigated all potential risk factors simultaneously in a structured manner allowing adjustment for confounders. Therefore, the aim of this case- control study was to identify risk factors for ARM among a wide spectrum of familial, pregnancy-related, lifestyle, and occupational factors in both mothers and fathers.
7
Abstract
Background Anorectal malformations (ARM) are major congenital malformations that
usually require a multitude of surgical procedures at very early age and have a large impact on the lives of patients and their parents. The causes of ARM are still largerly unknown, but it is assumed to have a multifactorial etiology. A few studies focused on environmental risk factors, but evidence is still scarce.
Methods In this Dutch case-control study (1996-2008), we investigated the role of maternal
and paternal risk factors in the etiology of ARM. Parents of 85 ARM cases and 650 controls filled in a questionnaire. Controls were children treated with ear ventilation tubes.
Results A higher occurrence of fever during the first trimester of pregnancy was found for
case mothers compared to control mothers (odds ratio (OR), 5.1; 95% Confidence Interval (CI), 0.9, 28.1). Maternal occupational exposure to industrial cleaning agents and solvents increased the risk of ARM three times (OR, 2.9; 95% CI, 0.9, 9.3). Overweight (Body Mass Index (BMI) ≥ 25 kg/m2) before pregnancy also seemed to be associated with ARM (OR, 1.8;
95% CI, 1.1, 2.8), as well as maternal multivitamin use during pregnancy (OR, 1.6; 95% CI, 1.0, 2.7), paternal smoking (OR, 1.8; 95% CI, 1.1, 2.9) and paternal occupational exposure to exhaust fumes (OR, 1.9; 95% CI, 1.0, 3.6). Reported ARM in at least one first or second degree family member greatly increased the risk of having a child with ARM (OR, 40.3; 95% CI, 4.8, 342.8).
Conclusions This study revealed potential risk factors for ARM, including fever during
pregnancy, maternal overweight, use of multivitamins, paternal smoking, and occupational exposures, but a familial component seems important as well.
Introduction
Congenital anorectal malformations (ARM) are the most common gastrointestinal anomalies at birth. The worldwide prevalence of ARM is estimated to be 1 in 1500 to 1 in 5000 live births.1 Anorectal anomalies include a wide range of phenotypes depending on location and
size of the defect. They usually require multiple surgical procedures at very early age and have a major impact on the lives of patients and their parents. Additional congenital anomalies are present in approximately 50% of ARM cases, especially anomalies of the heart, kidneys, spine, urogenital tract, and other gastrointestinal atresias, in particular as components of the VACTERL association (Vertebral defects, Anal atresia, Cardiac defects, Tracheo-Esophageal fistula, Renal anomalies, Radial dysplasia, and Limb defects). Not much is known about the etiology of ARM, apart from a few identified genes that have been implicated in syndromes including ARM or were derived from animal studies. Townes-Brocks syndrome, with combinations of anal, renal, limb, and ear anomalies, is caused by mutations in the SALL1 zinc-finger protein.2 Linkage and mutational analyses in patients with the Currarino syndrome, in which sacral malformations are found along with ARM, identified the homeobox gene HLXB9 as a major locus.3 Mutant mice with various defects in the signaling
pathway of sonic hedgehog exhibit a spectrum of distal hindgut defects mimicking human ARM, while mutant mice lacking Gli2 or Gli3 show imperforate anus with recto-urethral fistula and anal stenosis.4,5
Although evidence exists for genetic contribution to ARM based on these studies, nonsyndromic anorectal anomalies rarely aggregate in families.6 This points towards a
substantial role for environmental risk factors. A Japanese study suggested maternal alcohol drinking in early pregnancy as a risk factor for isolated anal atresia,7 that could not be
confirmed by others.8,9 Cigarette smoking and caffeine intake were found to be associated
with anal atresia in the US,9 whereas in France and Spain, associations with medical drug use during pregnancy were found,8 in particular use of the benzodiazepine lorazepam.10 Paternal
exposure to occupational hazards, such as organic solvents and metals in vehicle manufacturers seemed to be associated with anal atresia as well.8,11 Based on a single study
in China, it has been suggested that periconceptional folic acid supplementation may reduce the risk of anal atresia.12 Most of these potential risk factors stem from only one
epidemiologic study per risk factor, which is not sufficient for conclusions about causality. Moreover, none of these studies investigated all potential risk factors simultaneously in a structured manner allowing adjustment for confounders. Therefore, the aim of this case- control study was to identify risk factors for ARM among a wide spectrum of familial, pregnancy-related, lifestyle, and occupational factors in both mothers and fathers.