Gastroschisis in Europe – a case-malformed control study of medication and maternal illness during pregnancy as risk factors

Joanne Given, Maria Loane, Ester Garne, Vera Nelen, Ingeborg Barisic, Hanitra Randrianaivo, Babak Khoshnood, Awi Wiesel, Anke Rissmann, Catherine Lynch, Amanda, J. Neville, Anna Pierini, Marian Bakker, Kari Klungsoyr, Anna Latos Bielenska, Clara Cavero-Carbonell, Marie-Claude Addor, Natalya Zymak-Zakutnya, David Tucker, Helen Dolk

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Gastroschisis, a congenital anomaly of the abdomen, is associated with young maternal age and has increased in prevalence in many countries. Maternal illness and medication exposure are among environmental risk factors implicated in its aetiology.Methods: A population-based case-malformed control study was conducted using data from 18 European congenital anomaly registries, with information on first trimester medication use, covering 8 million births 1995-2012. 1,577 gastroschisis cases (of which 4% stillbirths, 11% terminations of pregnancy) were compared to 153,357 non-chromosomal/monogenic controls. Literature review identified previous associations concerning maternal illness and medication exposure to be tested as signals. Logistic regression adjusted for maternal age group, registry and time period was used to evaluate associations.Results: Comparing gastroschisis to other congenital anomalies, the data supported signals concerning maternal depression [aOR 2.52, 95% CI 1.45, 4.39], antidepressant use [aOR 2.03, 95% CI 1.22, 3.38], postnatal depression/psychosis following a previous pregnancy [aOR 8.32, 95% CI 2.56, 27.01], sexually transmitted infections [aOR 2.85, 95% CI 1.13, 7.24], topical antivirals [aOR 5.31, 95% CI 1.63, 17.33] and continuation of oral contraceptives in early pregnancy [aOR 2.17, 95% CI 1.13, 4.18]. Exploratory analyses suggested associations with a wider range of maternal infections and medications, including tonsillitis and the expectorant bromhexine. Conclusions: While it is difficult to disentangle the effects of the medication and underlying indication, our results add to the evidence base on preventable risk factors for gastroschisis. These risk factors may contribute to the higher risk among young mothers, and geographical and temporal variation in prevalence.
LanguageEnglish
Pages1-11
JournalPaediatric and Perinatal Epidemiology
VolumeOnline
Early online date25 Aug 2017
DOIs
Publication statusE-pub ahead of print - 25 Aug 2017

Fingerprint

Gastroschisis
Case-Control Studies
Mothers
Pregnancy
Maternal Age
Registries
Bromhexine
Expectorants
Postpartum Depression
Tonsillitis
Stillbirth
Environmental Exposure
First Pregnancy Trimester
Oral Contraceptives
Sexually Transmitted Diseases
Abdomen
Psychotic Disorders
Antidepressive Agents
Antiviral Agents
Age Groups

Keywords

  • Congenital anomaly
  • medication safety
  • gastroschisis
  • epidemiology

Cite this

Given, Joanne ; Loane, Maria ; Garne, Ester ; Nelen, Vera ; Barisic, Ingeborg ; Randrianaivo, Hanitra ; Khoshnood, Babak ; Wiesel, Awi ; Rissmann, Anke ; Lynch, Catherine ; Neville, Amanda, J. ; Pierini, Anna ; Bakker, Marian ; Klungsoyr, Kari ; Latos Bielenska, Anna ; Cavero-Carbonell, Clara ; Addor, Marie-Claude ; Zymak-Zakutnya, Natalya ; Tucker, David ; Dolk, Helen. / Gastroschisis in Europe – a case-malformed control study of medication and maternal illness during pregnancy as risk factors. In: Paediatric and Perinatal Epidemiology. 2017 ; Vol. Online. pp. 1-11.
@article{80c45b5edb9d4725b4247d1975789f77,
title = "Gastroschisis in Europe – a case-malformed control study of medication and maternal illness during pregnancy as risk factors",
abstract = "Background: Gastroschisis, a congenital anomaly of the abdomen, is associated with young maternal age and has increased in prevalence in many countries. Maternal illness and medication exposure are among environmental risk factors implicated in its aetiology.Methods: A population-based case-malformed control study was conducted using data from 18 European congenital anomaly registries, with information on first trimester medication use, covering 8 million births 1995-2012. 1,577 gastroschisis cases (of which 4{\%} stillbirths, 11{\%} terminations of pregnancy) were compared to 153,357 non-chromosomal/monogenic controls. Literature review identified previous associations concerning maternal illness and medication exposure to be tested as signals. Logistic regression adjusted for maternal age group, registry and time period was used to evaluate associations.Results: Comparing gastroschisis to other congenital anomalies, the data supported signals concerning maternal depression [aOR 2.52, 95{\%} CI 1.45, 4.39], antidepressant use [aOR 2.03, 95{\%} CI 1.22, 3.38], postnatal depression/psychosis following a previous pregnancy [aOR 8.32, 95{\%} CI 2.56, 27.01], sexually transmitted infections [aOR 2.85, 95{\%} CI 1.13, 7.24], topical antivirals [aOR 5.31, 95{\%} CI 1.63, 17.33] and continuation of oral contraceptives in early pregnancy [aOR 2.17, 95{\%} CI 1.13, 4.18]. Exploratory analyses suggested associations with a wider range of maternal infections and medications, including tonsillitis and the expectorant bromhexine. Conclusions: While it is difficult to disentangle the effects of the medication and underlying indication, our results add to the evidence base on preventable risk factors for gastroschisis. These risk factors may contribute to the higher risk among young mothers, and geographical and temporal variation in prevalence.",
keywords = "Congenital anomaly, medication safety, gastroschisis, epidemiology",
author = "Joanne Given and Maria Loane and Ester Garne and Vera Nelen and Ingeborg Barisic and Hanitra Randrianaivo and Babak Khoshnood and Awi Wiesel and Anke Rissmann and Catherine Lynch and Neville, {Amanda, J.} and Anna Pierini and Marian Bakker and Kari Klungsoyr and {Latos Bielenska}, Anna and Clara Cavero-Carbonell and Marie-Claude Addor and Natalya Zymak-Zakutnya and David Tucker and Helen Dolk",
note = "Reference text: 1 Rittler M, Vauthay L, Mazzitelli N. Gastroschisis is a defect of the Umbilical ring: Evidence from Morphological evaluation of stillborn fetuses. Birth Defects Research Part A: Clinical and Molecular Teratology 2013;97:198–209. 2 Bargy F, Beaudoin S. Comprehensive developmental mechanisms in gastroschisis. Fetal Diagnosis and Therapy 2014;36:223–230. 3 Ruano R, Picone O, Bernardes L, Martinovic J, Dumez Y, Benachi A. The association of gastroschisis with other congenital anomalies: how important is it? Prenatal Diagnosis 2011;31:347–50. 4 Feldkamp ML., Carey JC., Sadler TW. Development of Gastroschisis: Review of Hypotheses, a Novel Hypothesis, and Implications for Research. American Journal of Medical Genetics Part A 2007;143A:639–652. 5 Loane M., Dolk H., Bradbury I. Increasing prevalence of gastroschisis in Europe 1980-2002: a phenomenon restricted to younger mothers? Paediatric and Perinatal Epidemiology 2007;21:363–9. 6 Rittler M., Campana H., Ermini ML., Gili JA., Poletta FA., Pawluk MA., et al. Gastroschisis and young mothers: What makes them different from other mothers of the same age? Birth Defects Research Part A - Clinical and Molecular Teratology 2015;103:536–543. 7 Benjamin BG, Ethen MK, Van Hook CL, Myers C a, Canfield M a. Gastroschisis prevalence in Texas 1999-2003. Birth Defects Research. Part A, Clinical and Molecular Teratology 2010;88:178–85. 8 Whitehall JS, Kandasamy Y, Stalewski H, Gill A. Perinatal demography of gastroschisis in North Queensland. Journal of Paediatrics and Child Health 2010;46:749–753. 9 Werler MM., Mitchell AA., Moore CA., Honein MA. Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis? American Journal of Medical Genetics, Part A 2009;149:1399–1406. 10 Mac Bird T, Robbins JM. JM, Druschel CC., Cleves MA. MA, Yang S. S, Hobbs CA. CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. Journal of Pediatric Surgery 2009;44:1546–51. 11 Morrison JJ, Chitty LS, Peebles D, Rodeck CH, J.J. M, L.S. C, et al. Recreational drugs and fetal gastroschisis: maternal hair analysis in the peri-conceptional period and during pregnancy. British Journal of Obstetrics and Gynaecology: An International Journal of Obstetrics & Gynaecology 2005;112:1022–1025. 12 Alwan S., Reefhuis J., Rasmussen SA., Olney RS., Friedman JM., for the National Birth Defects Prevention Study.; Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. The New England Journal of Medicine 2007;356:2684–92. 13 Feldkamp ML., Reefhuis J., Kucik J., Krikov S., Wilson A., Moore CA., et al. Case-control study of self reported genitourinary infections and risk of gastroschisis: findings from the national birth defects prevention study, 1997-2003. British Medical Journal (Clinical Research Edition) 2008;336:1420–3. 14 Siega-Riz AM, Herring AH, Olshan AF, Smith J, Moore C. The joint effects of maternal prepregnancy body mass index and age on the risk of gastroschisis. Paediatric and Perinatal Epidemiology 2009;23:51–57. 15 Loane M, Dolk H, Kelly A, Teljeur C, Greenlees R, Densem J. Paper 4: EUROCAT statistical monitoring: identification and investigation of ten year trends of congenital anomalies in Europe. Birth Defects Research. Part A, Clinical and Molecular Teratology 2011;91 Suppl 1:S31-43. 16 Boyd PA., Haeusler M., Barisic I., Loane M., Garne E., Dolk H. Paper 1: The EUROCAT network-organization and processes. Birth Defects Research Part A - Clinical and Molecular Teratology 2011;91:2–15. 17 Bakker M., de Jonge L. EUROCAT Special Report: Sources of Information on Medication Use in Pregnancy. Newtownabbey: EUROCAT Central Registry; 2014. 18 Hook EB. Normal or affected controls in case-control studies of congenital malformations and other birth defects: reporting bias issues. Epidemiology 1993;4:182–4. 19 Schlesselman JJ. Case control studies: design, conduct, analysis. Oxford: Oxford University Press; 1982. 20 Dolk H, Wemakor A. Response to: Case–control studies require appropriate population controls: an example of error in the SSRI birth defect literature. European Journal of Epidemiology 2015;30:1219–1221. 21 Pharmacoepidemiology and Drug Safety. EUROmediCAT: Safety of Medication Use in Pregnancy. 2015;24:1–2. 22 Garne E, Dolk H, Loane M, Wellesley D, Barisic I, Calzolari E, et al. Paper 5: Surveillance of multiple congenital anomalies: implementation of a computer algorithm in European registers for classification of cases. Birth defects research. Part A, Clinical and molecular teratology 2011;91 Suppl 1:S44-50. 23 Lang JM., Rothman KJ., Cann CI. That Confounded P-Value. Epidemiology 1998;9:7–8. 24 Greenland S, Senn SJ, Rothman KJ, Carlin JB, Poole C, Goodman SN, et al. Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations. European Journal of Epidemiology 2016;31:337–350. 25 Reefhuis J., Devine O., Friedman JM., Louik C., Honein MA., for the National Birth Defects Prevention Study. Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. British Medical Journal 2015;350:h3190. 26 Werler MM., Sheehan JE., Mitchell AA. Maternal medication use and risks of gastroschisis and small intestinal atresia. American Journal of Epidemiology 2002;155:26–31. 27 Mart{\'i}nez-Fr{\'i}as ML, Rodr{\'i}guez-Pinilla E, Prieto L. Prenatal exposure to salicylates and gastroschisis: a case-control study. Teratology 1997;56:241–3. 28 Garne E, Hansen AV, Morris J, Zaupper L, Addor M-C, Barisic I, et al. Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study. The Journal of Allergy and Clinical Immunology 2015;136:1496–502. 29 Lin S., Munsie JPW., Herdt-Losavio ML., Bell E., Druschel C., Romitti PA., et al. Maternal asthma medication use and the risk of gastroschisis. American Journal of Epidemiology 2008;168:73–79. 30 Garne E, Loane M, Dolk H, Barisic I, Addor M-C, Arriola L, et al. Spectrum of congenital anomalies in pregnancies with pregestational diabetes. Birth Defects Research (Part A): Clinical and Molecular Teratology 2012;94:134–40. 31 Baer RJ, Chambers CD, Jones KL, Shew SB, MacKenzie TC, Shaw GM, et al. Maternal factors associated with the occurrence of gastroschisis. American Journal of Medical Genetics Part A 2015;167:1534–1541. 32 Waters CS., Hay DF., Simmonds JR., van Goozen SHM. Antenatal depression and children’s developmental outcomes: Potential mechanisms and treatment options. European Child & Adolescent Psychiatry 2014;23:957–971. 33 Cooper WO, Willy ME, Pont SJ, Ray WA. Increasing use of antidepressants in pregnancy. American Journal of Obstetrics and Gynecology 2007;196:544.e1-544.e5. 34 Bakker MK, K{\"o}lling P, van den Berg PB, de Walle HEK, de Jong van den Berg LTW. Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. British Journal of Clinical Pharmacology 2008;65:600–6. 35 Furu K., Kieler H., Haglund B., Engeland A., Selmer R., Stephansson O., et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: Population based cohort study and sibling design. British Medical Journal (Online) 2015;350. 36 Waller DK., Gallaway MS., Taylor LG., Ramadhani TA., Canfield MA., Scheuerle A., et al. Use of oral contraceptives in pregnancy and major structural birth defects in offspring. Epidemiology 2010;21:232–239. 37 Lubinsky M. Hypothesis: Estrogen related thrombosis explains the pathogenesis and epidemiology of gastroschisis. American Journal of Medical Genetics. Part A 2012;158A:808–11. 38 Ahrens KA., Anderka MT., Feldkamp ML., Canfield MA., Mitchell AA., Werler MM., et al. Antiherpetic medication use and the risk of gastroschisis: findings from the National Birth Defects Prevention Study, 1997-2007. Paediatric and Perinatal Epidemiology 2013;27:340–345. 39 Feldkamp ML., Enioutina EY., Botto LD., Krikov S., Byrne JLB., Geisler WM. Chlamydia trachomatis IgG3 seropositivity is associated with gastroschisis. Journal of Perinatology 2015;35:930–34. 40 Werler MM, Parker SE, Hedman K, Gissler M, Ritvanen A, Surcel H-M. Maternal Antibodies to Herpes Virus Antigens and Risk of Gastroschisis in Offspring. American Journal of Epidemiology 2016;184:902–912. 41 Feldkamp ML, Meyer RE, Krikov S, Botto LD. Acetaminophen use in pregnancy and risk of birth defects: findings from the National Birth Defects Prevention Study. Obstetrics and Gynecology 2010;115:109–115. 42 Norgard B, Puho E, Czeizel AE, Skriver M V, Sorensen HT. Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. American Journal of Obstetrics and Gynecology 2005;192:922–923. 43 Draper ES., Rankin J., Tonks AM., Abrams KR., Field DJ., Clarke M., et al. Recreational drug use: a major risk factor for gastroschisis? American Journal of Epidemiology 2008;167:485–491. 44 Skarsgard EDED., Meaney CC., Bassil K. K, Brindle M. M, Arbour L. L, Moineddin RR. Maternal risk factors for gastroschisis in Canada. Birth Defects Research Part A: Clinical and Molecular Teratology 2015;103:111–118. 45 Stothard KJ, Tennant PWG, Bell R. Maternal Overweight and Obesity and the Risk of Congenital Anomalies. Journal of the American Medical Association 2009;301:363–650. 46 Garne E, Vinkel Hansen A, Morris J, Jordan S, Klungs??yr K, Engeland A, et al. Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study. BJOG: An International Journal of Obstetrics and Gynaecology 2016;123:1609–1618. 47 de Jonge L., Garne E., Gini R., Jordan SE., Klungsoyr K., Loane M., et al. Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study. Drug Safety 2015;38:1083–93.",
year = "2017",
month = "8",
day = "25",
doi = "10.1111/ppe.12401",
language = "English",
volume = "Online",
pages = "1--11",
journal = "Paediatric and Perinatal Epidemiology",
issn = "0269-5022",

}

Given, J, Loane, M, Garne, E, Nelen, V, Barisic, I, Randrianaivo, H, Khoshnood, B, Wiesel, A, Rissmann, A, Lynch, C, Neville, AJ, Pierini, A, Bakker, M, Klungsoyr, K, Latos Bielenska, A, Cavero-Carbonell, C, Addor, M-C, Zymak-Zakutnya, N, Tucker, D & Dolk, H 2017, 'Gastroschisis in Europe – a case-malformed control study of medication and maternal illness during pregnancy as risk factors', Paediatric and Perinatal Epidemiology, vol. Online, pp. 1-11. https://doi.org/10.1111/ppe.12401

Gastroschisis in Europe – a case-malformed control study of medication and maternal illness during pregnancy as risk factors. / Given, Joanne; Loane, Maria; Garne, Ester; Nelen, Vera; Barisic, Ingeborg; Randrianaivo, Hanitra; Khoshnood, Babak; Wiesel, Awi; Rissmann, Anke; Lynch, Catherine; Neville, Amanda, J.; Pierini, Anna; Bakker, Marian; Klungsoyr, Kari; Latos Bielenska, Anna; Cavero-Carbonell, Clara; Addor, Marie-Claude; Zymak-Zakutnya, Natalya; Tucker, David; Dolk, Helen.

In: Paediatric and Perinatal Epidemiology, Vol. Online, 25.08.2017, p. 1-11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gastroschisis in Europe – a case-malformed control study of medication and maternal illness during pregnancy as risk factors

AU - Given, Joanne

AU - Loane, Maria

AU - Garne, Ester

AU - Nelen, Vera

AU - Barisic, Ingeborg

AU - Randrianaivo, Hanitra

AU - Khoshnood, Babak

AU - Wiesel, Awi

AU - Rissmann, Anke

AU - Lynch, Catherine

AU - Neville, Amanda, J.

AU - Pierini, Anna

AU - Bakker, Marian

AU - Klungsoyr, Kari

AU - Latos Bielenska, Anna

AU - Cavero-Carbonell, Clara

AU - Addor, Marie-Claude

AU - Zymak-Zakutnya, Natalya

AU - Tucker, David

AU - Dolk, Helen

N1 - Reference text: 1 Rittler M, Vauthay L, Mazzitelli N. Gastroschisis is a defect of the Umbilical ring: Evidence from Morphological evaluation of stillborn fetuses. Birth Defects Research Part A: Clinical and Molecular Teratology 2013;97:198–209. 2 Bargy F, Beaudoin S. Comprehensive developmental mechanisms in gastroschisis. Fetal Diagnosis and Therapy 2014;36:223–230. 3 Ruano R, Picone O, Bernardes L, Martinovic J, Dumez Y, Benachi A. The association of gastroschisis with other congenital anomalies: how important is it? Prenatal Diagnosis 2011;31:347–50. 4 Feldkamp ML., Carey JC., Sadler TW. Development of Gastroschisis: Review of Hypotheses, a Novel Hypothesis, and Implications for Research. American Journal of Medical Genetics Part A 2007;143A:639–652. 5 Loane M., Dolk H., Bradbury I. Increasing prevalence of gastroschisis in Europe 1980-2002: a phenomenon restricted to younger mothers? Paediatric and Perinatal Epidemiology 2007;21:363–9. 6 Rittler M., Campana H., Ermini ML., Gili JA., Poletta FA., Pawluk MA., et al. Gastroschisis and young mothers: What makes them different from other mothers of the same age? Birth Defects Research Part A - Clinical and Molecular Teratology 2015;103:536–543. 7 Benjamin BG, Ethen MK, Van Hook CL, Myers C a, Canfield M a. Gastroschisis prevalence in Texas 1999-2003. Birth Defects Research. Part A, Clinical and Molecular Teratology 2010;88:178–85. 8 Whitehall JS, Kandasamy Y, Stalewski H, Gill A. Perinatal demography of gastroschisis in North Queensland. Journal of Paediatrics and Child Health 2010;46:749–753. 9 Werler MM., Mitchell AA., Moore CA., Honein MA. Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis? American Journal of Medical Genetics, Part A 2009;149:1399–1406. 10 Mac Bird T, Robbins JM. JM, Druschel CC., Cleves MA. MA, Yang S. S, Hobbs CA. CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. Journal of Pediatric Surgery 2009;44:1546–51. 11 Morrison JJ, Chitty LS, Peebles D, Rodeck CH, J.J. M, L.S. C, et al. Recreational drugs and fetal gastroschisis: maternal hair analysis in the peri-conceptional period and during pregnancy. British Journal of Obstetrics and Gynaecology: An International Journal of Obstetrics & Gynaecology 2005;112:1022–1025. 12 Alwan S., Reefhuis J., Rasmussen SA., Olney RS., Friedman JM., for the National Birth Defects Prevention Study.; Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. The New England Journal of Medicine 2007;356:2684–92. 13 Feldkamp ML., Reefhuis J., Kucik J., Krikov S., Wilson A., Moore CA., et al. Case-control study of self reported genitourinary infections and risk of gastroschisis: findings from the national birth defects prevention study, 1997-2003. British Medical Journal (Clinical Research Edition) 2008;336:1420–3. 14 Siega-Riz AM, Herring AH, Olshan AF, Smith J, Moore C. The joint effects of maternal prepregnancy body mass index and age on the risk of gastroschisis. Paediatric and Perinatal Epidemiology 2009;23:51–57. 15 Loane M, Dolk H, Kelly A, Teljeur C, Greenlees R, Densem J. Paper 4: EUROCAT statistical monitoring: identification and investigation of ten year trends of congenital anomalies in Europe. Birth Defects Research. Part A, Clinical and Molecular Teratology 2011;91 Suppl 1:S31-43. 16 Boyd PA., Haeusler M., Barisic I., Loane M., Garne E., Dolk H. Paper 1: The EUROCAT network-organization and processes. Birth Defects Research Part A - Clinical and Molecular Teratology 2011;91:2–15. 17 Bakker M., de Jonge L. EUROCAT Special Report: Sources of Information on Medication Use in Pregnancy. Newtownabbey: EUROCAT Central Registry; 2014. 18 Hook EB. Normal or affected controls in case-control studies of congenital malformations and other birth defects: reporting bias issues. Epidemiology 1993;4:182–4. 19 Schlesselman JJ. Case control studies: design, conduct, analysis. Oxford: Oxford University Press; 1982. 20 Dolk H, Wemakor A. Response to: Case–control studies require appropriate population controls: an example of error in the SSRI birth defect literature. European Journal of Epidemiology 2015;30:1219–1221. 21 Pharmacoepidemiology and Drug Safety. EUROmediCAT: Safety of Medication Use in Pregnancy. 2015;24:1–2. 22 Garne E, Dolk H, Loane M, Wellesley D, Barisic I, Calzolari E, et al. Paper 5: Surveillance of multiple congenital anomalies: implementation of a computer algorithm in European registers for classification of cases. Birth defects research. Part A, Clinical and molecular teratology 2011;91 Suppl 1:S44-50. 23 Lang JM., Rothman KJ., Cann CI. That Confounded P-Value. Epidemiology 1998;9:7–8. 24 Greenland S, Senn SJ, Rothman KJ, Carlin JB, Poole C, Goodman SN, et al. Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations. European Journal of Epidemiology 2016;31:337–350. 25 Reefhuis J., Devine O., Friedman JM., Louik C., Honein MA., for the National Birth Defects Prevention Study. Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. British Medical Journal 2015;350:h3190. 26 Werler MM., Sheehan JE., Mitchell AA. Maternal medication use and risks of gastroschisis and small intestinal atresia. American Journal of Epidemiology 2002;155:26–31. 27 Martínez-Frías ML, Rodríguez-Pinilla E, Prieto L. Prenatal exposure to salicylates and gastroschisis: a case-control study. Teratology 1997;56:241–3. 28 Garne E, Hansen AV, Morris J, Zaupper L, Addor M-C, Barisic I, et al. Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study. The Journal of Allergy and Clinical Immunology 2015;136:1496–502. 29 Lin S., Munsie JPW., Herdt-Losavio ML., Bell E., Druschel C., Romitti PA., et al. Maternal asthma medication use and the risk of gastroschisis. American Journal of Epidemiology 2008;168:73–79. 30 Garne E, Loane M, Dolk H, Barisic I, Addor M-C, Arriola L, et al. Spectrum of congenital anomalies in pregnancies with pregestational diabetes. Birth Defects Research (Part A): Clinical and Molecular Teratology 2012;94:134–40. 31 Baer RJ, Chambers CD, Jones KL, Shew SB, MacKenzie TC, Shaw GM, et al. Maternal factors associated with the occurrence of gastroschisis. American Journal of Medical Genetics Part A 2015;167:1534–1541. 32 Waters CS., Hay DF., Simmonds JR., van Goozen SHM. Antenatal depression and children’s developmental outcomes: Potential mechanisms and treatment options. European Child & Adolescent Psychiatry 2014;23:957–971. 33 Cooper WO, Willy ME, Pont SJ, Ray WA. Increasing use of antidepressants in pregnancy. American Journal of Obstetrics and Gynecology 2007;196:544.e1-544.e5. 34 Bakker MK, Kölling P, van den Berg PB, de Walle HEK, de Jong van den Berg LTW. Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. British Journal of Clinical Pharmacology 2008;65:600–6. 35 Furu K., Kieler H., Haglund B., Engeland A., Selmer R., Stephansson O., et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: Population based cohort study and sibling design. British Medical Journal (Online) 2015;350. 36 Waller DK., Gallaway MS., Taylor LG., Ramadhani TA., Canfield MA., Scheuerle A., et al. Use of oral contraceptives in pregnancy and major structural birth defects in offspring. Epidemiology 2010;21:232–239. 37 Lubinsky M. Hypothesis: Estrogen related thrombosis explains the pathogenesis and epidemiology of gastroschisis. American Journal of Medical Genetics. Part A 2012;158A:808–11. 38 Ahrens KA., Anderka MT., Feldkamp ML., Canfield MA., Mitchell AA., Werler MM., et al. Antiherpetic medication use and the risk of gastroschisis: findings from the National Birth Defects Prevention Study, 1997-2007. Paediatric and Perinatal Epidemiology 2013;27:340–345. 39 Feldkamp ML., Enioutina EY., Botto LD., Krikov S., Byrne JLB., Geisler WM. Chlamydia trachomatis IgG3 seropositivity is associated with gastroschisis. Journal of Perinatology 2015;35:930–34. 40 Werler MM, Parker SE, Hedman K, Gissler M, Ritvanen A, Surcel H-M. Maternal Antibodies to Herpes Virus Antigens and Risk of Gastroschisis in Offspring. American Journal of Epidemiology 2016;184:902–912. 41 Feldkamp ML, Meyer RE, Krikov S, Botto LD. Acetaminophen use in pregnancy and risk of birth defects: findings from the National Birth Defects Prevention Study. Obstetrics and Gynecology 2010;115:109–115. 42 Norgard B, Puho E, Czeizel AE, Skriver M V, Sorensen HT. Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. American Journal of Obstetrics and Gynecology 2005;192:922–923. 43 Draper ES., Rankin J., Tonks AM., Abrams KR., Field DJ., Clarke M., et al. Recreational drug use: a major risk factor for gastroschisis? American Journal of Epidemiology 2008;167:485–491. 44 Skarsgard EDED., Meaney CC., Bassil K. K, Brindle M. M, Arbour L. L, Moineddin RR. Maternal risk factors for gastroschisis in Canada. Birth Defects Research Part A: Clinical and Molecular Teratology 2015;103:111–118. 45 Stothard KJ, Tennant PWG, Bell R. Maternal Overweight and Obesity and the Risk of Congenital Anomalies. Journal of the American Medical Association 2009;301:363–650. 46 Garne E, Vinkel Hansen A, Morris J, Jordan S, Klungs??yr K, Engeland A, et al. Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study. BJOG: An International Journal of Obstetrics and Gynaecology 2016;123:1609–1618. 47 de Jonge L., Garne E., Gini R., Jordan SE., Klungsoyr K., Loane M., et al. Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study. Drug Safety 2015;38:1083–93.

PY - 2017/8/25

Y1 - 2017/8/25

N2 - Background: Gastroschisis, a congenital anomaly of the abdomen, is associated with young maternal age and has increased in prevalence in many countries. Maternal illness and medication exposure are among environmental risk factors implicated in its aetiology.Methods: A population-based case-malformed control study was conducted using data from 18 European congenital anomaly registries, with information on first trimester medication use, covering 8 million births 1995-2012. 1,577 gastroschisis cases (of which 4% stillbirths, 11% terminations of pregnancy) were compared to 153,357 non-chromosomal/monogenic controls. Literature review identified previous associations concerning maternal illness and medication exposure to be tested as signals. Logistic regression adjusted for maternal age group, registry and time period was used to evaluate associations.Results: Comparing gastroschisis to other congenital anomalies, the data supported signals concerning maternal depression [aOR 2.52, 95% CI 1.45, 4.39], antidepressant use [aOR 2.03, 95% CI 1.22, 3.38], postnatal depression/psychosis following a previous pregnancy [aOR 8.32, 95% CI 2.56, 27.01], sexually transmitted infections [aOR 2.85, 95% CI 1.13, 7.24], topical antivirals [aOR 5.31, 95% CI 1.63, 17.33] and continuation of oral contraceptives in early pregnancy [aOR 2.17, 95% CI 1.13, 4.18]. Exploratory analyses suggested associations with a wider range of maternal infections and medications, including tonsillitis and the expectorant bromhexine. Conclusions: While it is difficult to disentangle the effects of the medication and underlying indication, our results add to the evidence base on preventable risk factors for gastroschisis. These risk factors may contribute to the higher risk among young mothers, and geographical and temporal variation in prevalence.

AB - Background: Gastroschisis, a congenital anomaly of the abdomen, is associated with young maternal age and has increased in prevalence in many countries. Maternal illness and medication exposure are among environmental risk factors implicated in its aetiology.Methods: A population-based case-malformed control study was conducted using data from 18 European congenital anomaly registries, with information on first trimester medication use, covering 8 million births 1995-2012. 1,577 gastroschisis cases (of which 4% stillbirths, 11% terminations of pregnancy) were compared to 153,357 non-chromosomal/monogenic controls. Literature review identified previous associations concerning maternal illness and medication exposure to be tested as signals. Logistic regression adjusted for maternal age group, registry and time period was used to evaluate associations.Results: Comparing gastroschisis to other congenital anomalies, the data supported signals concerning maternal depression [aOR 2.52, 95% CI 1.45, 4.39], antidepressant use [aOR 2.03, 95% CI 1.22, 3.38], postnatal depression/psychosis following a previous pregnancy [aOR 8.32, 95% CI 2.56, 27.01], sexually transmitted infections [aOR 2.85, 95% CI 1.13, 7.24], topical antivirals [aOR 5.31, 95% CI 1.63, 17.33] and continuation of oral contraceptives in early pregnancy [aOR 2.17, 95% CI 1.13, 4.18]. Exploratory analyses suggested associations with a wider range of maternal infections and medications, including tonsillitis and the expectorant bromhexine. Conclusions: While it is difficult to disentangle the effects of the medication and underlying indication, our results add to the evidence base on preventable risk factors for gastroschisis. These risk factors may contribute to the higher risk among young mothers, and geographical and temporal variation in prevalence.

KW - Congenital anomaly

KW - medication safety

KW - gastroschisis

KW - epidemiology

U2 - 10.1111/ppe.12401

DO - 10.1111/ppe.12401

M3 - Article

VL - Online

SP - 1

EP - 11

JO - Paediatric and Perinatal Epidemiology

T2 - Paediatric and Perinatal Epidemiology

JF - Paediatric and Perinatal Epidemiology

SN - 0269-5022

ER -