Maternal risk factors for the VACTERL association: A EUROCAT case-control study

Romy van de Putte; Iris A. L. M. Van Rooij; Cynthia P. Haanappel; Carlo L. M. Marcelis; Han G. Brunner; Marie-Claude Addor; Clara Cavero-Carbonell; Carlos M. Dias; Elizabeth S. Draper; Larraitz Etxebarriarteun; Miriam Gatt; Babak Khoshnood; Agnieszka Kinsner-Ovaskainen; Kari Klungsoyr; Jenny J. Kurinczuk; Anna Latos-Bielenska; Karen Luyt; Mary T. O'Mahony; Nicola Miller; Carmel Mullaney; Vera Nelen; Amanda J. Neville; Isabelle Perthus; Anna Pierini; Hanitra Randrianaivo; Judith Rankin; Anke Rissmann; Florence Rouget; Bruno Schaub; David Tucker; Diana Wellesley; Awi Wiesel; Natalya Zymak-Zakutnia; Maria Loane; Ingeborg Barisic; Hermien E. K. De   Walle; Jorieke E. H. Bergman; Nel Roeleveld

doi:10.1002/bdr2.1686

Maternal risk factors for the VACTERL association: A EUROCAT case-control study

Romy van de Putte^*, Iris A. L. M. Van Rooij, Cynthia P. Haanappel, Carlo L. M. Marcelis, Han G. Brunner, Marie-Claude Addor, Clara Cavero-Carbonell, Carlos M. Dias, Elizabeth S. Draper, Larraitz Etxebarriarteun, Miriam Gatt, Babak Khoshnood, Agnieszka Kinsner-Ovaskainen, Kari Klungsoyr, Jenny J. Kurinczuk, Anna Latos-Bielenska, Karen Luyt, Mary T. O'Mahony, Nicola Miller, Carmel MullaneyVera Nelen, Amanda J. Neville, Isabelle Perthus, Anna Pierini, Hanitra Randrianaivo, Judith Rankin, Anke Rissmann, Florence Rouget, Bruno Schaub, David Tucker, Diana Wellesley, Awi Wiesel, Natalya Zymak-Zakutnia, Maria Loane, Ingeborg Barisic, Hermien E. K. De Walle, Jorieke E. H. Bergman, Nel Roeleveld

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown.

Objective To identify maternal risk factors for VACTERL in offspring in a large European study.

Methods A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI).

Results The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4]).

Conclusion We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology.

Original language	English
Pages (from-to)	688-698
Number of pages	11
Journal	Birth Defects Research
Volume	112
Issue number	9
DOIs	https://doi.org/10.1002/bdr2.1686
Publication status	Published - 15 May 2020

Keywords

etiology
assisted reproductive techniques
maternal factors
pregestational diabetes
respiratory disorders
STRUCTURAL BIRTH-DEFECTS
ANORECTAL-MALFORMATIONS
REPRODUCTIVE TECHNOLOGIES
CONGENITAL-ANOMALIES
DISORDERS
SELECTION
ETIOLOGY

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van de Putte, R., Van Rooij, I. A. L. M., Haanappel, C. P., Marcelis, C. L. M., Brunner, H. G., Addor, M.-C., Cavero-Carbonell, C., Dias, C. M., Draper, E. S., Etxebarriarteun, L., Gatt, M., Khoshnood, B., Kinsner-Ovaskainen, A., Klungsoyr, K., Kurinczuk, J. J., Latos-Bielenska, A., Luyt, K., O'Mahony, M. T., Miller, N., ... Roeleveld, N. (2020). Maternal risk factors for the VACTERL association: A EUROCAT case-control study. Birth Defects Research, 112(9), 688-698. https://doi.org/10.1002/bdr2.1686

@article{7f7a1a3a303e4bd0aab987329f4658bf,

title = "Maternal risk factors for the VACTERL association: A EUROCAT case-control study",

abstract = "Background The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown.Objective To identify maternal risk factors for VACTERL in offspring in a large European study.Methods A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI).Results The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4]).Conclusion We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology.",

keywords = "etiology, assisted reproductive techniques, maternal factors, pregestational diabetes, respiratory disorders, STRUCTURAL BIRTH-DEFECTS, ANORECTAL-MALFORMATIONS, REPRODUCTIVE TECHNOLOGIES, CONGENITAL-ANOMALIES, DISORDERS, SELECTION, ETIOLOGY",

author = "{van de Putte}, Romy and {Van Rooij}, {Iris A. L. M.} and Haanappel, {Cynthia P.} and Marcelis, {Carlo L. M.} and Brunner, {Han G.} and Marie-Claude Addor and Clara Cavero-Carbonell and Dias, {Carlos M.} and Draper, {Elizabeth S.} and Larraitz Etxebarriarteun and Miriam Gatt and Babak Khoshnood and Agnieszka Kinsner-Ovaskainen and Kari Klungsoyr and Kurinczuk, {Jenny J.} and Anna Latos-Bielenska and Karen Luyt and O'Mahony, {Mary T.} and Nicola Miller and Carmel Mullaney and Vera Nelen and Neville, {Amanda J.} and Isabelle Perthus and Anna Pierini and Hanitra Randrianaivo and Judith Rankin and Anke Rissmann and Florence Rouget and Bruno Schaub and David Tucker and Diana Wellesley and Awi Wiesel and Natalya Zymak-Zakutnia and Maria Loane and Ingeborg Barisic and {De Walle}, {Hermien E. K.} and Bergman, {Jorieke E. H.} and Nel Roeleveld",

note = "Funding Information: We would like to thank the parents of the patients included in our study and all those involved in the EUROCAT registries that participated, in particular the people that were involved in providing and processing the information of the patients, including clinicians, health professionals, medical record clerks, and registry staff. RvdP was supported by a personal research grant from the Radboud university medical center, Nijmegen, the Netherlands. EUROCAT registries are funded as fully described in the EUROCAT. Funding Information: We would like to thank the parents of the patients included in our study and all those involved in the EUROCAT registries that participated, in particular the people that were involved in providing and processing the information of the patients, including clinicians, health professionals, medical record clerks, and registry staff. RvdP was supported by a personal research grant from the Radboud university medical center, Nijmegen, the Netherlands. EUROCAT registries are funded as fully described in the EUROCAT. ?Members & Registry Descriptions? ({"}EUROCAT, 2019a; Kinsner-Ovaskainen et al., 2018). Publisher Copyright: {\textcopyright} 2020 The Authors. Birth Defects Research published by Wiley Periodicals, Inc.",

year = "2020",

month = may,

day = "15",

doi = "10.1002/bdr2.1686",

language = "English",

volume = "112",

pages = "688--698",

journal = "Birth Defects Research",

issn = "2472-1727",

publisher = "Wiley",

number = "9",

}

van de Putte, R, Van Rooij, IALM, Haanappel, CP, Marcelis, CLM, Brunner, HG, Addor, M-C, Cavero-Carbonell, C, Dias, CM, Draper, ES, Etxebarriarteun, L, Gatt, M, Khoshnood, B, Kinsner-Ovaskainen, A, Klungsoyr, K, Kurinczuk, JJ, Latos-Bielenska, A, Luyt, K, O'Mahony, MT, Miller, N, Mullaney, C, Nelen, V, Neville, AJ, Perthus, I, Pierini, A, Randrianaivo, H, Rankin, J, Rissmann, A, Rouget, F, Schaub, B, Tucker, D, Wellesley, D, Wiesel, A, Zymak-Zakutnia, N, Loane, M, Barisic, I, De Walle, HEK, Bergman, JEH & Roeleveld, N 2020, 'Maternal risk factors for the VACTERL association: A EUROCAT case-control study', Birth Defects Research, vol. 112, no. 9, pp. 688-698. https://doi.org/10.1002/bdr2.1686

TY - JOUR

T1 - Maternal risk factors for the VACTERL association

T2 - A EUROCAT case-control study

AU - van de Putte, Romy

AU - Van Rooij, Iris A. L. M.

AU - Haanappel, Cynthia P.

AU - Marcelis, Carlo L. M.

AU - Brunner, Han G.

AU - Addor, Marie-Claude

AU - Cavero-Carbonell, Clara

AU - Dias, Carlos M.

AU - Draper, Elizabeth S.

AU - Etxebarriarteun, Larraitz

AU - Gatt, Miriam

AU - Khoshnood, Babak

AU - Kinsner-Ovaskainen, Agnieszka

AU - Klungsoyr, Kari

AU - Kurinczuk, Jenny J.

AU - Latos-Bielenska, Anna

AU - Luyt, Karen

AU - O'Mahony, Mary T.

AU - Miller, Nicola

AU - Mullaney, Carmel

AU - Nelen, Vera

AU - Neville, Amanda J.

AU - Perthus, Isabelle

AU - Pierini, Anna

AU - Randrianaivo, Hanitra

AU - Rankin, Judith

AU - Rissmann, Anke

AU - Rouget, Florence

AU - Schaub, Bruno

AU - Tucker, David

AU - Wellesley, Diana

AU - Wiesel, Awi

AU - Zymak-Zakutnia, Natalya

AU - Loane, Maria

AU - Barisic, Ingeborg

AU - De Walle, Hermien E. K.

AU - Bergman, Jorieke E. H.

AU - Roeleveld, Nel

N1 - Funding Information: We would like to thank the parents of the patients included in our study and all those involved in the EUROCAT registries that participated, in particular the people that were involved in providing and processing the information of the patients, including clinicians, health professionals, medical record clerks, and registry staff. RvdP was supported by a personal research grant from the Radboud university medical center, Nijmegen, the Netherlands. EUROCAT registries are funded as fully described in the EUROCAT. Funding Information: We would like to thank the parents of the patients included in our study and all those involved in the EUROCAT registries that participated, in particular the people that were involved in providing and processing the information of the patients, including clinicians, health professionals, medical record clerks, and registry staff. RvdP was supported by a personal research grant from the Radboud university medical center, Nijmegen, the Netherlands. EUROCAT registries are funded as fully described in the EUROCAT. ?Members & Registry Descriptions? ("EUROCAT, 2019a; Kinsner-Ovaskainen et al., 2018). Publisher Copyright: © 2020 The Authors. Birth Defects Research published by Wiley Periodicals, Inc.

PY - 2020/5/15

Y1 - 2020/5/15

N2 - Background The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown.Objective To identify maternal risk factors for VACTERL in offspring in a large European study.Methods A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI).Results The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4]).Conclusion We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology.

AB - Background The VACTERL association (VACTERL) is the nonrandom occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Despite suggestions for involvement of several genes and nongenetic risk factors from small studies, the etiology of VACTERL remains largely unknown.Objective To identify maternal risk factors for VACTERL in offspring in a large European study.Methods A case-control study was performed using data from 28 EUROCAT registries over the period 1997-2015 with case and control ascertainment through hospital records, birth and death certificates, questionnaires, and/or postmortem examinations. Cases were diagnosed with VACTERL, while controls had a genetic syndrome and/or chromosomal abnormality. Data collected included type of birth defect and maternal characteristics, such as age, use of assisted reproductive techniques (ART), and chronic illnesses. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) with 95% confidence intervals (95% CI).Results The study population consisted of 329 VACTERL cases and 49,724 controls with recognized syndromes or chromosomal abnormality. For couples who conceived through ART, we found an increased risk of VACTERL (aOR 2.3 [95% CI 1.3, 3.9]) in offspring. Pregestational diabetes (aOR 3.1 [95% CI 1.1, 8.6]) and chronic lower obstructive pulmonary diseases (aOR 3.9 [95% CI 2.2, 6.7]) also increased the risk of having a child with VACTERL. Twin pregnancies were not associated with VACTERL (aOR 0.6 [95% CI 0.3, 1.4]).Conclusion We identified several maternal risk factors for VACTERL in offspring befitting a multifactorial etiology.

KW - etiology

KW - assisted reproductive techniques

KW - maternal factors

KW - pregestational diabetes

KW - respiratory disorders

KW - STRUCTURAL BIRTH-DEFECTS

KW - ANORECTAL-MALFORMATIONS

KW - REPRODUCTIVE TECHNOLOGIES

KW - CONGENITAL-ANOMALIES

KW - DISORDERS

KW - SELECTION

KW - ETIOLOGY

U2 - 10.1002/bdr2.1686

DO - 10.1002/bdr2.1686

M3 - Article

C2 - 32319733

SN - 2472-1727

VL - 112

SP - 688

EP - 698

JO - Birth Defects Research

JF - Birth Defects Research

IS - 9

ER -

Maternal risk factors for the VACTERL association: A EUROCAT case-control study

Abstract

Keywords

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