Acessibilidade / Reportar erro

Maternal smoking during pregnancy and birth defects in children: a systematic review with meta-analysis

El tabaquismo materno durante el embarazo y las malformaciones congénitas en niños: una revisión sistemática y meta-análisis

Abstracts

This systematic review aimed to investigate the association between maternal smoking during pregnancy and birth defects in children. We performed an electronic search of observational studies in the databases ovid MEDLINE (1950 to April 2010), LILACS and SciELO. We included 188 studies with a total of 13,564,914 participants (192,655 cases). Significant positive associations were found between maternal smoking and birth defects in the following body systems: cardiovascular (OR: 1.11; 95%CI: 1.03-1.19), digestive (OR: 1.18; 95%CI: 1.07-1.30), musculoskeletal (OR: 1.27; 95%CI: 1.16-1.39) and face and neck (OR: 1.28; 95%CI: 1.19-1.37). The strength of association between maternal smoking and birth defects measured by the OR (95%CI) is significantly related to the amount of cigarettes smoked daily (χ2 = 12.1; df = 2; p = 0.002). In conclusion, maternal smoking during pregnancy is associated with congenital malformations in children and this association is dose-dependent.

Smoking; Pregnancy; Congenital Abnormalities


Esta revisión sistemática se encargó de investigar la asociación entre el tabaquismo materno durante el embarazo y las malformaciones congénitas en los niños. Se realizó una búsqueda electrónica de los estudios de observación en las bases de datos de ovid MEDLINE (1950 hasta abril de 2010), LILACS y SciELO. 188 estudios con 13.564.914 participantes se incluyeron en esta revisión. Se encontraron asociaciones positivas significativas entre el tabaquismo materno y malformaciones de los sistemas: cardiovascular (OR: 1,11; IC95%: 1.03-1.19), digestivo (OR: 1,18; IC95%: 1,07-1,30), musculoesqueléticos (OR: 1,27; IC95%: 1,16-1,39) y de cara y cuello (OR: 1,28; IC95%: 1,19-1,37). La fuerza de la asociación entre el tabaquismo materno y los defectos de nacimiento, medidos por el OR (IC95%) está significativamente relacionada con la cantidad de cigarrillos fumados diariamente (χ2 = 12,1; p = 0,002). Llegamos a la conclusión de que el tabaquismo materno durante el embarazo se asocia con un mayor riesgo de malformaciones congénitas en los niños y esta asociación es dosis-dependiente.

Hábito de Fumar; Embarazo; Anomalías Congénitas


Esta revisão sistemática teve como objetivo investigar a associação entre fumo materno na gestação e as malformações congênitas em crianças. Uma busca eletrônica dos estudos observacionais foi realizada nas bases de dados ovid MEDLINE (1950 até abril de 2010), SciELO e LILACS. Foram incluídos nesta revisão 188 estudos com um total de 13.564.914 participantes (192.655 casos). Foram encontradas associações positivas significativas entre fumo materno e malformações dos sistemas: cardiovascular (OR: 1,11; IC95%: 1,03-1,19), digestivo (OR: 1,18; IC95%: 1,07-1,30), musculoesquelético (OR: 1,27; IC95%: 1,16-1,39) e face e pescoço (OR: 1,28; IC95%: 1,19-1,37). A força de associação entre fumo materno e malformações medida pelo OR (IC95%) está relacionada significativamente com a quantidade diária de cigarros consumidos (χ2 = 12,1; df = 2; p = 0,002). Concluímos que fumo materno na gestação está associado com maior risco de malformações congênitas em crianças e essa associação é dose-dependente.

Hábito de Fumar; Gravidez; Anormalidades Congênitas


Introduction

Birth defects are the cause of high mortality and morbidity in children. It is estimated that about 5% of live births present some abnormality in their development11. Horovitz DDG, Llerena Jr. JC, Mattos RA. Atenção aos defeitos congênitos no Brasil: panorama atual. Cad Saúde Pública 2005; 21:1055-64.. Over the past decades, birth defects have increasingly contributed to child mortality22. Powell-Griner E, Woolbright A. Trends in infant deaths from congenital anomalies: results from England and Wales, Scotland, Sweden and the United States. Int J Epidemiol 1990; 19:391-8. , 33. Neto PS, Zhang L, Nicoletti D, Munchen FB. Mortalidade infantil por malformações congênitas no Brasil. Rev AMRIGS 2012; 56:129-32.. In Brazil, the rate of child deaths due to birth defects rose from 9.7% in 1996 to 18.2% in 2008, representing an annual average increase of 0.71%33. Neto PS, Zhang L, Nicoletti D, Munchen FB. Mortalidade infantil por malformações congênitas no Brasil. Rev AMRIGS 2012; 56:129-32.. This increase may be due to a better management of infections and contagious, and nutrition-related diseases, which reduced child deaths from these conditions 11. Horovitz DDG, Llerena Jr. JC, Mattos RA. Atenção aos defeitos congênitos no Brasil: panorama atual. Cad Saúde Pública 2005; 21:1055-64. , 33. Neto PS, Zhang L, Nicoletti D, Munchen FB. Mortalidade infantil por malformações congênitas no Brasil. Rev AMRIGS 2012; 56:129-32..

Most birth defects are of multifactorial etiology. In addition to the genetic component, their occurrence may be related to exposure of the child, even before birth, or the parents to toxic substances, including tobacco44. Stillerman KP, Mattison DR, Giudice LC, Woodruff TJ. Environmental exposures and adverse pregnancy outcomes: a review of the science. Reprod Sci 2008; 15:631-50.. While this investigation was being carried out, a systematic review with 101 observational studies was published, and showed an association between maternal smoking during pregnancy and different birth defects in children 55. Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173687 malformed cases and 11.7 million controls. Hum Reprod Updat 2011; 17:589-604.. This review, however, did not include a considerable number of relevant studies66. Bird TM, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51. , 77. Bracken MB, Holford TR, White C, Kelsey JL. Role of oral contraception in congenital malformations of offspring. Int J Epidemiol 1978; 7:309-17. , 88. Cedergren MI, Selbing AJ, Källén BAJ. Risk factors for cardiovascular malformation - a study based on prospectively collected data. Scan J Work Environ Health 2002; 28:12-7. , 99. Christensen K, Olsen J, Norgaard-Pedersen B, Basso O, Stovring H, Milhollin-Johnson L, et al. Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994. Am J Epidemiol 1999; 149:248-55. , 1010. DeRoo LA, Gaudino JA, Edmonds LD. Orofacial cleft malformations: associations with maternal and infant characteristics in Washington state. Birth Defects Res A Clin Mol Teratol 2003; 67: 637-42. , 1111. Dickinson KC, Meyer RE, Kotch J. Maternal smoking and the risk for clubfoot in infants. Birth Defects Res A Clin Mol Teratol 2008; 82:86-91. , 1212. Feldkamp ML, Alder SC, Carey JC. A case control population-based study investigating smoking as a risk factor for gastroschisis in Utah, 1997-2005. Birth Defects Res A Clin Mol Teratol 2008; 82: 768-75. , 1313. Ramirez D, Lammer EJ, Iovannisci DM, Laurent C, Finnell RH, Shaw GM. Maternal smoking during early pregnancy, GSTP1 and EPHX1 variants, and risk of isolated orofacial clefts. Cleft Palate Craniofac J 2007; 44:366-73. , 1414. Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors and risk for ventricular septal defects. Birth Defects Res A Clin Mol Teratol 2004; 70:59-64.. Moreover, defects of the abdominal wall, such as congenital diaphragmatic and inguinal hernia, gastroschisis, and omphalocele, which should be considered musculoskeletal abnormalities, according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10)1515. Centro Colaborador da OMS para a Classificação de Doenças em Português. Classificação estatística internacional de doenças e problemas relacionados à saúde. 10a revisão. http://www.datasus.gov.br/cid10/V2008/cid10.htm (accessed on 20/Apr/2010).
http://www.datasus.gov.br/cid10/V2008/ci...
were classified as gastrointestinal defects.

The purpose of this systematic review is to investigate maternal smoking during pregnancy and birth defects in children. The possible dose-response relation in that association was also studied.

Methods

A systematic review with meta-analysis was conducted. The procedures for the review and reporting of the results were based on the recommendations by MOOSE (Meta-analysis of Observational Studies in Epidemiology) 1616. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000; 283:2008-12.. The protocol for the review was assessed and approved by a panel that included two experts in Pediatrics and one in Epidemiology, in 2010.

Studies that investigated the association between maternal smoking during pregnancy and birth defects in children were considered eligible for the review. Studies that contemplated the association between maternal smoking and chromosomal abnormalities were ruled out.

The electronic search of the studies was made on databases Ovid MEDLINE (1950 until April 2010), SciELO, and LILACS. The strategy to search potentially relevant studies for the review on the databse Ovid MEDLINE is composed of two parts (Figure 1): the first (from line #1 to line #4) is the search strategy to identify studies on maternal smoking, and the secons part (from line #5 to line #20) is the strategy to find birth-defects-related studies. The bibliographic references of articles whose full text was obtained were reviewed, in order to identify additional studies. The Google Translator (https://translate.google.com.br/) was used to translate two articles, one in Lithuanian and other in French.

Figure 1
Search strategy of studies in the Ovid MEDLINE database.

Study selection was independently made by four investigators (two teams of two). Selection process was made in two stages: in the first, the title and abstract of the articles identified during the electronic search were reviewed to select potential studies for this review. The full text of articles was obtained for which information from the title and the abstract met the inclusion criteria, or in cases where there was not enough information to decide about their inclusion. In the second stage, the articles were read in full for a final selection of the studies, with the inclusion and exclusion criteria being checked. Discrepancies among the investigators were resolved by consensus. Data extraction was performed by four investigators using a standard form. The extracted data were checked by the investigators.

Meta-analysis was performed using the software Stata, version 11.0 (Stata Corp., College Station, United States). A random effects model was applied. The association between maternal smoking during pregnancy and the presence of any kind of birth defects in children was evaluated by means of odds ratios (OR) and 95% confidence intervals (95%CI). When the original studies indicated the presence of more than one defect, the results of each defect were combined to obtain data of any type of defect. Whenever possible, adjusted OR was used.

The pre-defined sub-group analyses were performed to investigate the association between maternal smoking during pregnancy and birth defects in children, according to the organ systems involved. The classification of birth defects was based on the ICD-10. The pre-defined sub-group analyses were also used to assess the potential influence of the following methodological aspects in the results of the meta-analyses: design of the investigation (prospective vs. retrospective); size of the sample (cases) (≤ 200; 200-1,000; 1,000-5,000; > 5,000); adjustment/matching of confounding factors, including age of the mother (yes vs. no). Two post hocsubgroup analyses were performed to assess the potential impact of exposure definition (maternal smoking), and the period of exposure during pregnancy in the meta-analysis results. To investigate the dose-response relation between maternal smoking during pregnancy and birth defects in children, the analysis was stratified in three categories according to the number of cigarettes smoked per day (1-9, 10-19 and > 20).

Heterogeneity of results among the studies was assessed through the I22. Powell-Griner E, Woolbright A. Trends in infant deaths from congenital anomalies: results from England and Wales, Scotland, Sweden and the United States. Int J Epidemiol 1990; 19:391-8. statistic. I22. Powell-Griner E, Woolbright A. Trends in infant deaths from congenital anomalies: results from England and Wales, Scotland, Sweden and the United States. Int J Epidemiol 1990; 19:391-8. > 75% indicates significant heterogeneity1717. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analysis. BMJ 2003; 327:557-60.. Possible causes for heterogeneity were examined through the above mentioned sub-group analyses. The publication bias was investigated with the use of the funnel plot and the Egger test1717. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analysis. BMJ 2003; 327:557-60..

Results

Out of the 1,043 citations identified by the electronic search, 129 studies were selected. Fifty-nine additional studies were included, found in reviews of original articles and from the systematic review. Therefore, a total of 188 studies (153 projects or independent databases) 66. Bird TM, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51. , 77. Bracken MB, Holford TR, White C, Kelsey JL. Role of oral contraception in congenital malformations of offspring. Int J Epidemiol 1978; 7:309-17. , 88. Cedergren MI, Selbing AJ, Källén BAJ. Risk factors for cardiovascular malformation - a study based on prospectively collected data. Scan J Work Environ Health 2002; 28:12-7. , 99. Christensen K, Olsen J, Norgaard-Pedersen B, Basso O, Stovring H, Milhollin-Johnson L, et al. Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994. Am J Epidemiol 1999; 149:248-55. , 1010. DeRoo LA, Gaudino JA, Edmonds LD. Orofacial cleft malformations: associations with maternal and infant characteristics in Washington state. Birth Defects Res A Clin Mol Teratol 2003; 67: 637-42. , 1111. Dickinson KC, Meyer RE, Kotch J. Maternal smoking and the risk for clubfoot in infants. Birth Defects Res A Clin Mol Teratol 2008; 82:86-91. , 1212. Feldkamp ML, Alder SC, Carey JC. A case control population-based study investigating smoking as a risk factor for gastroschisis in Utah, 1997-2005. Birth Defects Res A Clin Mol Teratol 2008; 82: 768-75. , 1313. Ramirez D, Lammer EJ, Iovannisci DM, Laurent C, Finnell RH, Shaw GM. Maternal smoking during early pregnancy, GSTP1 and EPHX1 variants, and risk of isolated orofacial clefts. Cleft Palate Craniofac J 2007; 44:366-73. , 1414. Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors and risk for ventricular septal defects. Birth Defects Res A Clin Mol Teratol 2004; 70:59-64. , 1818. Adams MM, Mulinare J, Dooley K. Risk factors for conotruncal cardiac defects in Atlanta. J Am Coll Cardiol 1989; 14:432-42. , 1919. Akre O, Lipworth L, Cnattingius S, Sparen P, Ekbom A. Risk factor patterns for cryptorchidism and hypospadias. Epidemiology 1999; 10:364-9. , 2020. Alderman BW, Takahashi ER, LeMier MK. Risk indicators for talipes equinovarus in Washington State, 1987-1989. Epidemiology 1991; 2:289-92. , 2121. Alderman BW, Bradley CM, Greene C, Fernbach SK, Baron AE. Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy. Teratology 1994; 50:13-8. , 2222. Ananijevic-Pandey J, Jarebinski M, Kastratovic B, Vlajinac H, Radojkovic Z, Brankovic D. Case-control study of congenital malformations. Eur J Epidemiol 1992; 8:871-4. , 2323. Aro T. Maternal diseases, alcohol consumption and smoking during pregnancy associated with reduction limb defects. Early Hum Dev 1983; 9: 49-57. , 2424. Bailey RR. The effect of maternal smoking on the infant birth weight. N Z Med J 1970; 71:293-4. , 2525. Batra M, Heike CL, Phillips RC, Weiss NS. Geographic and occupational risk factors for ventricular septal defects: Washington State, 1987-2003. Arch Pediatr Adolesc Med 2007; 161:89-95. , 2626. Beard CM, Melton LJ, O'Fallon WM, Noller KL, Benson RC. Cryptorchism and maternal estrogen exposure. Am J Epidemiol 1984; 120:707-16. , 2727. Beaty TH, Maestri NE, Hetmanski JB, Wyszynski DF, Vanderkolk CA, Simpson JC, et al. Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992-1996. Cleft Palate Craniofac J 1997; 34: 447-54. , 2828. Beaty TH, Wang H, Hetmanski JB, Fan YT, Zeiger JS, Liang KY, et al. A case-control study of nonsyndromic oral clefts in Maryland. Ann Epidemiol 2001; 11:434-42. , 2929. Bell R, Lumley J. Alcohol consumption, cigarette smoking and fetal outcome in Victoria, 1985. Community Health Stud 1989; 13:484-91. , 3030. Berkowitz GS, Lapinski RH. Risk factors for cryptorchidism: a nested case-control study. Paediatr Perinat Epidemiol 1996; 10:39-51. , 3131. Biggs ML, Baer A, Critchlow CW. Maternal, delivery, and perinatal characteristics associated with cryptorchidism: a population-based case-control study among births in Washington State. Epidemiology 2002; 13:197-204. , 3232. Bille C, Olsen J, Vach W, Knudsen VK, Olsen SF, Rasmussen K, et al. Oral clefts and life style factors: a case-cohort study based on prospective Danish data. Eur J Epidemiol 2007; 22:173-81. , 3333. Bitsko RH, Reefhuis J, Romitti PA, Moore CA, Honein MA. Periconceptional consumption of vitamins containing folic acid and risk for multiple congenital anomalies. Am J Med Genet A 2007; 143A:2397-405. , 3434. Blatter BM, Roeleveld N, Zielhuis GA, Gabreels FJ, Verbeek AL. Maternal occupational exposure during pregnancy and the risk of spina bifida. Occup Environ Med 1996; 53:80-6. , 3535. Botto LD, Lynberg MC, Erickson JD. Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study. Epidemiology 2001; 12:485-90. , 3636. Brouwers MM, Feitz WF, Roelofs LA, Kiemeney LA, de Gier RP, Roeleveld N. Risk factors for hypospadias. Eur J Pediatr 2007; 166:671-8. , 3737. Brouwers MM, van der Zanden LF, de Gier RP, Barten EJ, Zielhuis GA, Feitz WF, et al. Hypospadias: risk factor patterns and different phenotypes. BJU Int. 2010; 105:254-62. , 3838. Browne ML, Bell EM, Druschel CM, Gensburg LJ, Mitchell AA, Lin AE, et al. Maternal caffeine consuption and risk of cardiovascular malformations. Birth Defects Res A Clin Mol Teratol 2007; 79: 533-43. , 3939. Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, et al. The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. Int J Androl 2007; 30:3-13. , 4040. Cardy AH, Barker S, Chesney D, Sharp L, Maffulli N, Miedzybrodzka Z. Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study. BMC Musculoskelet Disord 2007; 8:62. , 4141. Carmichael SL, Shaw GM. Maternal life event stress and congenital anomalies. Epidemiology 2000; 11:30-5. , 4242. Carmichael SL, Nelson V, Shaw GM, Wasserman CR, Croen LA. Socio-economic status and risk of conotruncal heart defects and orofacial clefts. Paediatr Perinat Epidemiol 2003; 17:264-71. , 4343. Carmichael SL, Shaw GM, Laurent C, Lammer EJ, Olney RS. Hypospadias and maternal exposures to cigarette smoke. Pediatr Perinat Epidemiol 2005; 19:406-12. , 4444. Carmichael SL, Ma C, Rasmussen SA, Honein MA, Lammer EJ, Shaw GM. Craniosynostosis and maternal smoking. Birth Defects Res A Clin Mol Teratol 2008; 82:78-85. , 4545. Caton AR, Bell EM, Druschel CM, Werler MM, Mitchell AA, Browne ML, et al. Maternal hypertension, antihypertensive medication use, and the risk of severe hypospadias. Birth Defects Res A Clin Mol Teratol 2008; 82:34-40. , 4646. Chambers CD, Chen BH, Kalla K, Jernigan L, Jones KL. Novel risk factor in gastroschisis: change of paternity. Am J Med Genet A 2007; 143A:653-9. , 4747. Chevrier C, Bahuau M, Perret C, Iovannisci DM, Nelva A, Herman C, et al. Genetic susceptibilities in the association between maternal exposure to tobacco smoke and the risk of nonsyndromic oral cleft. Am J Med Genet A 2008; 146A:2396-406. , 4848. Chew E, Remaley NA, Tamboli A, Zhao J, Podgor MJ, Klebanoff M. Risk factors for esotropia and exotropia. Arch Ophthalmol 1994; 112:1349-55. , 4949. Christianson RE. The relationship between maternal smoking and the incidence of congenital anomalies. Am J Epidemiol 1980; 112:684-95. , 5050. Chung CS, Myrianthopoulos NC. Factors affecting risks of congenital malformations. I. Analysis of epidemiologic factors in congenital malformations. Report from the Collaborative Perinatal Project. Birth Defects Orig Artic Ser 1975; 11:1-22. , 5151. Chung KC, Kowalski CP, Kim HM, Buchman SR. Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate. Plast Reconstr Surg 2000; 105:485-91. , 5252. Cordier S, Ha MC, Ayme S, Goujard J. Maternal occupational exposure and congenital malformations. Scand J Work Environ Health 1992; 18:11-7. , 5353. Correy JF, Newman NM, Collins JA, Burrows EA, Burrows RF, Curran JT. Use of prescription drugs in the first trimester and congenital malformations. Aust N Z J Obstet Gynaecol 1991; 31:340-4. , 5454. Croen LA, Shaw GM, Lammer EJ. Risk factors for cytogenetically normal holoprosencephaly in California: a population-based case-control study. Am J Med Genet 2000; 90:320-5. , 5555. Czeizel A, Vitez M. Etiological study of omphalocele. Hum Genet 1981; 58:390-5. , 5656. Czeizel A, Nagy E. A recent aetiological study on facial clefting in Hungary. Acta Paediatr Hung 1986; 27:145-66. , 5757. Czeizel AE, Kodaj I, Lenz W. Smoking during pregnancy and congenital limb deficiency. BMJ 1994; 308:1473-6. , 5858. Czeizel AE, Petik D, Puho E. Smoking and alcohol drinking during pregnancy. The reliability of retrospective maternal self-reported information. Cent Eur J Public Health 2004; 12:179-83. , 5959. Costa CMS, Gama SGN, Leal MC. Congenital malformations in Rio de Janeiro, Brazil: prevalence and associated factors. Cad Saúde Pública 2006; 22:2423-31. , 6060. Damgaard IN, Jensen TK; Nordic Cryptorchidism Study Group; Petersen JH, Skakkebaek NE, Toppari J, et al. Risk factors for congenital cryptorchidism in a prospective birth cohort study. PLoS One 2008; 3:e3051. , 6161. Davies TW, Williams DR, Whitaker RH. Risk factors for undescended testis. Int J Epidemiol 1986; 15:197-201. , 6262. Draper ES, Rankin J, Tonks A, Boyd P, Wellesley D, Tucker D, et al. Recreational drug use: a major risk factor for gastroschisis? Am J Epidemiol 2008; 167:485-91. , 6363. Erickson JD. Risk factors for birth defects: data from the Atlanta Birth Defects Case-Control Study. Teratology 1991; 43:41-51. , 6464. Ericson A, Kallen B, Westerholm P. Cigarette smoking as an etiologic factor in cleft lip and palate. Am J Obstet Gynecol 1979; 135:348-51. , 6565. Evans DR, Newcombe RG, Campbell H. Maternal smoking habits and congenital malformations: a population study. Br Med J 1979; 2:171-3. , 6666. Fedrick J, Alberman ED, Goldstein H. Possible teratogenic effect of cigarette smoking. Nature 1971; 231:529-30. , 6767. Felix JF, van Dooren MF, Klaassens M, Hop WC, Torfs CP, Tibboel D. Environmental factors in the etiology of esophageal atresia and congenital diaphragmatic hernia: results of a case-control study. Birth Defects Res A Clin Mol Teratol 2008; 82: 98-105. , 6868. Ferencz C, Loffredo CA, Correa-Villasenor A. Genetic and environmental risk factors of major cardiovascular malformations: The Baltimore-Washington Infant Study 1981-1989. Armonk: Futura Publishing Co.; 1997. , 6969. Garcia AM, Fletcher T, Benavides FG, Orts E. Parental agricultural work and selected congenital malformations. Am J Epidemiol 1999; 149:64-74. , 7070. Goldbaum G, Daling J, Milham S. Risk factors for gastroschisis. Teratology 1990; 42:397-403. , 7171. Golding J, Butler NR. Maternal smoking and anencephaly. Br Med J (Clin Res Ed) 1983; 287:533-4. , 7272. Grewal J, Carmichael SL, Ma C, Lammer EJ, Shaw GM. Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies. Birth Defects Res A Clin Mol Teratol 2008; 82:519-26. , 7373. Haddow JE, Palomaki GE, Holman MS. Young maternal age and smoking during pregnancy as risk factors for gastroschisis. Teratology 1993; 47:225-8. , 7474. Hakim RB, Tielsch JM. Maternal cigarette smoking during pregnancy. A risk factor for childhood strabismus. Arch Ophthalmol 1992; 110:1459-62. , 7575. Hearey CD, Harris JA, Usatin MS, Epstein DM, Ury HK, Neutra RR. Investigation of a cluster of anencephaly and spina bifida. Am J Epidemiol 1984; 120:559-64. , 7676. Heinonen OP. Birth defects and drugs in pregnancy. Littleton: Publishing Sciences Group, Inc.; 1977. , 7777. Hemminki K, Mutanen P, Saloniemi I, Luoma K. Congenital malformations and maternal occupation in Finland: multivariate analysis. J Epidemiol Community Health 1981; 35:5-10. , 7878. Himmelberger DU, Brown Jr. BW, Cohen EN. Cigarette smoking during pregnancy and the occurrence of spontaneous abortion and congenital abnormality. Am J Epidemiol 1978; 108:470-9. , 7979. Hobbs CA, James SJ, Jernigan S, Melnyk S, Lu Y, Malik S, et al. Congenital heart defects, maternal homocysteine smoking, and the 677 C>T polymorphism in the methylenetetrahydroflate reductase gene: evaluating gene-environment interactions. Am J Obstet Gynecol 2006; 194:218-24. , 8080. Honein MA, Paulozzi LJ, Moore CA. Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction. Am J Epidemiol 2000; 152:658-65. , 8181. Honein MA, Rasmussen SA. Further evidence for an association between maternal smoking and craniosynostosis. Teratology 2000; 62:145-6. , 8282. Honein MA, Paulozzi LJ, Watkins ML. Maternal smoking and birth defects: validity of birth certificate data for effect estimation. Public Health Rep 2001; 116:327-35. , 8383. Honein MA, Rasmussen SA, Reefhuis J, Romitti PA, Lammer EJ, Sun L, et al. Maternal smoking and environmental tobacco smoke exposure and the risk of orofacial clefts. Epidemiology 2007; 18:226-33. , 8484. Hougland KT, Hanna AM, Meyers R, Null D. Increasing prevalence of gastroschisis in Utah. J Pediatr Surg 2005; 40:535-40. , 8585. Jensen MS, Toft G, Thulstrup AM, Bonde JP, Olsen J. Cryptorchidism according to maternal gestational smoking. Epidemiology 2007; 18:220-5. , 8686. Johansen AM, Wilcox AJ, Lie RT, Andersen LF, Drevon CA. Maternal consumption of coffee and caffeine-containing beverages and oral clefts: a population-based case-control study in Norway. Am J Epidemiol 2009; 169:1216-22. , 8787. Jones ME, Swerdlow AJ, Griffith M, Goldacre MJ. Prenatal risk factors for cryptorchidism: a record linkage study. Paediatr Perinat Epidemiol 1998; 12:383-96. , 8888. Kallen K. Maternal smoking and craniosynostosis. Teratology 1999; 60:146-50. , 8989. Kallen K. Multiple malformations and maternal smoking. Paediatr Perinat Epidemiol 2000; 14: 227-33. , 9090. Kelsey JL, Dwyer T, Holford TR, Bracken MB. Maternal smoking and congenital malformations: an epidemiological study. J Epidemiol Community Health 1978; 32:102-7. , 9191. Khoury MJ, Gomez-Farias M, Mulinare J. Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring? Am J Dis Child 1989; 143:333-7. , 9292. Krapels IP, Zielhuis GA, Vroom F, de Jong-van den Berg LT, Kuijpers-Jagtman AM, van der Molen AB, et al. Periconceptional health and lifestyle factors of both parents affect the risk of live-born children with orofacial clefts. Birth Defects Res A Clin Mol Teratol 2006; 76:613-20. , 9393. Krauss MJ, Morrissey AE, Winn HN, Amon E, Leet TL. Microcephaly: an epidemiologic analysis. Am J Obstet Gynecol 2003; 188:1484-9. , 9494. Kricker A, Elliott JW, Forrest JM, McCredie J. Congenital limb reduction deformities and use of oral contraceptives. Am J Obstet Gynecol 1986; 155:1072-8. , 9595. Kuciene R, Dulskiene V. Maternal socioeconomic and lifestyle factors during pregnancy and the risk of congenital heart defects. Medicina (Kaunas) 2009; 45:904-9. , 9696. Kullander S, Kallen B. A prospective study of smoking and pregnancy. Acta Obstet Gynecol Scand 1971; 50:83-94. , 9797. Kurahashi N, Kasai S, Shibata T, Kakizaki H, Nonomura K, Sata F, et al. Parental and neonatal risk factors for cryptorchidism. Med Sci Monit 2005; 11:CR274-83. , 9898. Kurahashi N, Sata F, Kasai S, Shibata T, Moriya K, Yamada H, et al. Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias. Mol Hum Reprod 2005; 11:93-8. , 9999. Lam PK, Torfs CP. Interaction between maternal smoking and malnutrition in infant risk of gastroschisis. Birth Defects Res A Clin Mol Teratol 2006; 76:182-6. , 100100. Leite IC, Koifman S. Oral clefts, consanguinity, parental tobacco and alcohol use: a case-control study in Rio de Janeiro, Brazil. Pesqui Odontol Bras 2009; 23:31-7. , 101101. Li DK, Mueller BA, Hickok DE, Daling JR, Fantel AG, Checkoway H, et al. Maternal smoking during pregnancy and the risk of congenital urinary tract anomalies. Am J Public Health 1996; 86: 249-53. , 102102. Li Z, Ren A, Zhang L, Guo Z, Li Z. A population-based case-control study of risk factors for neural tube defects in four high-prevalence areas of Shanxi province, China. Paediatr Perinat Epidemiol 2006; 20:43-53. , 103103. Lie RT, Wilcox AJ, Taylor J, Gjessing HK, Saugstad OD, Aabyholm F, et al. Maternal smoking and oral clefts. Epidemiology 2008; 19:606-15. , 104104. Lieff S, Olshan AF, Werler M, Strauss RP, Smith J, Mitchell A. Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns. Am J Epidemiol 1999; 150:683-94. , 105105. Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ryan KJ. Lack of association between contraceptive usage and congenital malformations in offspring. Am J Obstet Gynecol 1983; 147:923-8. , 106106. Little J, Cardy A, Arslan MT, Gilmour M, Mossey PA. Smoking and orofacial clefts: a United Kingdom-based case-control study. Cleft Palate Craniofac J 2004; 41:381-6. , 107107. Liu S, Liu J, Tang J, Ji J, Chen J, Liu C. Environmental risk factors for congenital heart disease in the Shandong Peninsula, China: a hospital-based case-control study. J Epidemiol 2009; 19:122-30. , 108108. Lorente C, Cordier S, Goujard J, Aymé S, Bianchi F, Calzolari E, et al. Tobacco and alcohol use during pregnancy and risk of oral clefts. Am J Public Health 2000; 90:415-9. , 109109. Lowe CR. Effect of mothers' smoking habits on birth weight of their children. Br Med J 1959; 2:673-6. , 110110. Lubs ML. Racial differences in maternal smoking effects on the newborn infant. Am J Obstet Gynecol 1973; 115:66-76. , 111111. Lumley J, Correy JF, Newman NM, Curran JT. Cigarette smoking, alcohol consumption and fetal outcome in Tasmania 1981-82. Aust N Z J Obstet Gynaecol 1985; 25:33-40. , 112112. MacBird T, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51. , 113113. Malik S, Cleves MA, Honein MA, Romitti PA, Botto LD, Yang S, et al. Maternal smoking and congenital heart defects. Pediatrics 2008; 121:e810-6. , 114114. Malloy MH, Kleinman JC, Bakewell JM, Schramm WF, Land GH. Maternal smoking during pregnancy: no association with congenital malformations in Missouri 1980-83. Am J Public Health 1989; 79:1243-6. , 115115. Man LX, Chang B. Maternal cigarette smoking during pregnancy increases the risk of having a child with a congenital digital anomaly. Plast Reconst Surg 2006; 117:301-8. , 116116. Mandiracioglu A, Ulman I, Luleci E, Ulman C. The incidence and risk factors of neural tube defects in Izmir, Turkey: a nested case-control study. Turk J Pediatr 2004; 46:214-20. , 117117. Martinez-Frias ML, Rodriguez-Pinilla E, Prieto L. Prenatal exposure to salicylates and gastroschisis: a case-control study. Teratology 1997; 56: 241-3. , 118118. McBride ML, van den Steen N, Lamb CW, Gallagher RP. Maternal and gestational factors in cryptorchidism. Int J Epidemiol 1991; 20:964-70. , 119119. McDonald AD, Armstrong BG, Sloan M. Cigarette, alcohol, and coffee consumption and congenital defects. Am J Public Health 1992; 82:91-3. , 120120. McGlynn KA, Graubard BI, Klebanoff MA, Longnecker MP. Risk factors for cryptorchism among populations at differing risks of testicular cancer. Int J Epidemiol 2006; 35:787-95. , 121121. Miller EA, Manning SE, Rasmussen SA, Reefhuis J, Honein MA; National Birth Defects Prevention Study. Maternal exposure to tobacco smoke, alcohol and caffeine, and risk of anorectal atresia: National Birth Defects Prevention Study 1997-2003. Paediatr Perinat Epidemiol 2009; 23:9-17. , 122122. Miller EA, Rasmussen SA, Siega-Riz AM, Frías JL, Honein MA. Risk factors for non-syndromic holoprosencephaly in the national birth defects prevention study. Am J Med Genet C Semin Med Genet 2010; 154C:62-72. , 123123. Mitchell LE, Murray JC, O'Brien S, Christensen K. Evaluation of two putative susceptibility loci for oral clefts in the Danish population. Am J Epidemiol 2001; 153:1007-15. , 124124. Morales-Suárez-Varela MM, Bille C, Christensen K, Olsen J. Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol 2006; 107:51-7. , 125125. Morgana LM, Cohn BA, Cohen RD, Christianson RE. Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies Cohort, 1959-1967. Am J Epidemiol 2008; 167:257-61. , 126126. Mori M, Davies TW, Tsukamoto T, Kumamoto Y, Fukuda K. Maternal and other factors of cryptorchidism: a case-control study in Japan. Kurume Med J 1992; 39:53-60. , 127127. Mossey PA, Davies JA, Little J. Prevention of orofacial clefts: does pregnancy planning have a role? Cleft Palate Craniofac J 2007; 44:244-50. , 128128. Munoz JB, Lacasana M, Aburto VHB, Sanchez LET, Garcia AMG, Carrillo LL. Socioeconomic factors and the risk of anencephaly in a Mexican population: a case-control study. Public Health Rep 2005; 120:39-45. , 129129. Mygind H, Thulstrup AM, Pedersen L, Larsen H. Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy. Acta Obstet Gynecol Scand 2002; 81:234-9. , 130130. Niebyl JR, Blake DA, Rocco LE, Baumgardner R, Mellits ED. Lack of maternal metabolic, endocrine, and environmental influences in the etiology of cleft lip with or without cleft palate. Cleft Palate J 1985; 22:20-8. , 131131. Nørgaard M, Wogelius P, Pedersen L, Rothman KJ, Sørensen HT. Maternal use of oral contraceptives during early pregnancy and risk of hypospadias in male offspring. Urology 2009; 74:583-7. , 132132. Oddsberg J, Jia C, Nilsson E, Ye W, Lagergren J. Maternal tobacco smoking, obesity, and low socioeconomic status during early pregnancy in the etiology of esophageal atresia. J Pediatr Surg 2008; 43:1791-5. , 133133. Ormond G, Nieuwenhuijsen MJ, Nelson P, Toledano MB, Iszatt N, Geneletti S, et al. Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ Health Perspect 2009; 117:303-7. , 134134. Parikh CR, McCall D, Engelman C, Schrier RW. Congenital renal agenesis: case-control analysis of birth characteristics. Am J Kidney Dis 2002 39:689-94. , 135135. Parker SE, Mai CT, Strickland MJ, Olney RS, Rickard R, Marengo L, et al. Multistate study of the epidemiology of clubfoot. Birth Defects Res A Clin Mol Teratol 2009; 85:897-904. , 136136. Pierik FH, Burdorf A, Deddens JA, Juttmann RE, Weber RF. Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Environ Health Perspect 2004; 112:1570-6. , 137137. Porter MP, Faizan MK, Grady RW, Mueller BA. Hypospadias in Washington State: maternal risk factors and prevalence trends. Pediatrics 2005; 115:e495-9. , 138138. Preiksa RT, Zilaitiene B, Matulevicius V, Skakkebaek NE, Petersen JH, Jorgensen N, et al. Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod 2005; 20:1928-32. , 139139. Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J. Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998). Arch Gynecol Obstet 2002; 266: 163-7. , 140140. Rantakallio P. Relationship of maternal smoking to morbidity and mortality of the child up to the age of five. Acta Paediatr Scand 1978; 67:621-31. , 141141. Reefhuis J, de Walle HE, Cornel MC. Maternal smoking and deformities of the foot: results of the EUROCAT Study. European Registries of Congenital Anomalies. Am J Public Health 1998; 88:1554-5. , 142142. Robitaille J, Carmichael SL, Shaw GM, Olney RS; National Birth Defects Prevention Study. Maternal nutrient intake and risks for transverse and longitudinal limb deficiencies: data from the National Birth Defects Prevention Study, 1997-2003. Birth Defects Res A Clin Mol Teratol 2009; 85: 773-9. , 143143. Rodríguez-Pinilla E, Mejías C, Prieto-Merino D, Fernández P, Martínez-Frias ML; ECEMC Working Group. Risk of hypospadias in newborn infants exposed to valproic acid during the first trimester of pregnancy: a case-control study in Spain. Drug Saf 2008; 31:537-43. , 144144. Romitti PA, Sun L, Honein MA, Reefhuis J, Correa A, Rasmussen SA. Maternal periconceptional alcohol consumption and risk of orofacial clefts. Am J Epidemiol 2007; 166:775-85. , 145145. Salemi JL, Pierre M, Tanner JP, Kornosky JL, Hauser KW, Kirby RS, et al. Maternal nativity as a risk factor for gastroschisis: a population-based study. Birth Defects Res A Clin Mol Teratol 2009; 85:890-6. , 146146. Saxen I. Cleft lip and palate in Finland: parental histories, course of pregnancy and selected environmental factors. Int J Epidemiol 1974; 3: 263-70. , 147147. Schmidt RJ, Romitti PA, Burns TL, Browne ML, Druschel CM, Olney RS. Maternal caffeine consumption and risk of neural tube defects. Birth Defects Res A Clin Mol Teratol 2009; 85:879-89. , 148148. Seidman DS, Ever-Hadani P, Gale R. Effect of maternal smoking and age on congenital anomalies. Obstet Gynecol 1990; 76:1046-50. , 149149. Shaw GM, Malcoe LH, Swan SH, Cummins SK, Schulman J. Congenital cardiac anomalies relative to selected maternal exposures and conditions during early pregnancy. Eur J Epidemiol 1992; 8:757-60. , 150150. Shaw GM, Wasserman CR, Lammer EJ, O'Malley CD, Murray JC, Basart AM, et al. Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants. Am J Hum Genet 1996; 58:551-61. , 151151. Shaw GM, Velie EM, Morland KB. Parental recreational drug use and risk for neural tube defects. Am J Epidemiol 1996; 144:1155-60. , 152152. Shaw GM, Wasserman CR, O'Malley CD, Nelson V, Jackson RJ. Maternal pesticide exposure from multiple sources and selected congenital anomalies. Epidemiology 1999; 10:60-6. , 153153. Shaw GM, Croen LA, Todoroff K, Tolarova MM. Periconceptional intake of vitamin supplements and risk of multiple congenital anomalies. Am J Med Genet 2000; 93:188-93. , 154154. Shi M, Christensen K, Weinberg CR, Romitti P, Bathum L, Lozada A, et al. Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants. Am J Hum Genet 2007; 80:76-90. , 155155. Shiono PH, Klebanoff MA, Berendes HW. Congenital malformations and maternal smoking during pregnancy. Teratology 1986; 34:65-71. , 156156. Skelly AC, Holt VL, Mosca VS, Alderman BW. Talipes equinovarus and maternal smoking: a population-based case-control study in Washington state. Teratology 2002; 66:91-100. , 157157. Slickers JE, Olshan AF, Siega-Riz AM, Honein MA, Aylsworth AS. Maternal body mass index and lifestyle exposures and the risk of bilateral renal agenesis or hypoplasia: the National Birth Defects Prevention Study. Am J Epidemiol 2008; 168:1259-67. , 158158. Smedts HP, de Vries JH, Rakhshandehroo M, Wildhagen MF, Verkleij-Hagoort AC, Steegers EA, et al. High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring. BJOG 2009; 116:416-23. , 159159. Sorensen HT, Norgard B, Pedersen L, Larsen H, Johnsen SP. Maternal smoking and risk of hypertrophic infantile pyloric stenosis: 10 year population based cohort study. BMJ 2002; 325:1011-2. , 160160. Steinberger EK, Ferencz C, Loffredo CA. Infants with single ventricle: a population-based epidemiological study. Teratology 2002; 65:106-15. , 161161. Stoll C, Alembik Y, Roth MP, Dott B. Risk factors in congenital anal atresias. Ann Genet 1997; 40: 197-204. , 162162. Stoll C, Alembik Y, Dott B, Roth MP. Risk factors in congenital abdominal wall defects (omphalocele and gastroschisi): a study in a series of 265,858 consecutive births. Ann Genet 2001; 44:201-8. ,163.164, 165165. Tamura T, Munger RG, Corcoran C, Bacayao JY, Nepomuceno B, Solon F. Plasma zinc concentrations of mothers and the risk of nonsyndromic oral clefts in their children: a case-control study in the Philippines. Birth Defects Res A Clin Mol Teratol 2005; 73:612-6. , 166166. Targett CS, Ratten GJ, Abell DA, Beischer NA. The influence of smoking on intrauterine fetal growth and on maternal oestriol excretion. Aust N Z J Obstet Gynecol 1977; 17:126-30. , 167167. Tata LJ, Lewis SA, McKeever TM, Smith CJ, Doyle P, Smeeth L, et al. Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study. Thorax 2008; 63:981-7. , 168168. The NS, Honein MA, Caton AR, Moore CA, Siega-Riz AM, Druschel CM. Risk factors for isolated biliary atresia, National Birth Defects Prevention Study, 1997-2002. Am J Med Genet A 2007; 143A:2274-84. , 169169. Tikkanen J, Heinonen OP. Maternal exposure to chemical and physical factors during pregnancy and cardiovascular malformations in the offspring. Teratology 1991; 43:591-600. , 170170. To WW, Tang MH. The association between maternal smoking and fetal hydranencephaly. J Obstet Gynaecol Res 1999; 25:39-42. , 171171. Torfs CP, Velie EM, Oechsli FW, Bateson TF, Curry CJ. A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 1994; 50:44-53. , 172172. Tornqvist K, Ericsson A, Kallen B. Optic nerve hypoplasia: risk factors and epidemiology. Acta Ophthalmol Scand 2002; 80:300-4. , 173173. Torp-Pedersen T, Boyd HA, Poulsen G, Haargaard B, Wohlfahrt J, Holmes JM, et al. In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus. Am J Epidemiol 2010; 171:868-75. , 174174. Tuohy PG, Counsell AM, Geddis DC. The Plunket National Child Health Study: birth defects and sociodemographic factors. N Z Med J 1993; 106:489-92. , 175175. Underwood P, Hester LL, Laffitte Jr. T, Gregg KV. The relationship of smoking to the outcome of pregnancy. Am J Obstet Gynecol 1965; 91:270-6. , 176176. van den Boogaard MJ, de Costa D, Krapels IP, Liu F, van Duijn C, Sinke RJ, et al. The MSX1 allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts. Hum Genet 2008; 124:525-34. , 177177. van den Eeden SK, Karagas MR, Daling JR, Vaughan TL. A case-control study of maternal smoking and congenital malformations. Paediatr Perinat Epidemiol 1990; 4:147-55. , 178178. van Rooij IA, Wegerif MJ, Roelofs HM, Peters WH, Kuijpers-Jagtman AM, Zielhuis GA, et al. Smoking, genetic polymorphisms in biotransformation enzymes, and nonsyndromic oral clefting: a gene-environment interaction. Epidemiology 2001; 12:502-7. , 179179. van Rooij IA, Groenen PM, van Drongelen M, Te Morsche RH, Peters WH, Steegers-Theunissen RP. Orofacial clefts and spina bifida: N-acetyltransferase phenotype, maternal smoking, and medication use. Teratology 2002; 66:260-6. , 180180. Verkerk PH, Buitendijk SE, Verloove-Vanhorick SP. Differential misclassification of alcohol and cigarette consumption by pregnancy outcome. Int J Epidemiol 1994; 23:1218-25. , 181181. Virtanen HE, Tapanainen AE, Kaleva MM, Suomi AM, Main KM, Skakkebaek NE, et al. Mild gestational diabetes as a risk factor for congenital cryptorchidism. J Clin Endocrinol Metab 2006; 91:4862-5. , 182182. Wang W, Guan P, Xu W, Zhou B. Risk factors for oral clefts: a population-based case-control study in Shenyang, China. Paediatr Perinat Epidemiol 2009; 23:310-20. , 183183. Wasserman CR, Shaw GM, O'Malley CD, Tolarova MM, Lammer EJ. Parental cigarette smoking and risk for congenital anomalies of the heart, neural tube, or limb. Teratology 1996; 53:261-7. , 184184. Watkins ML, Scanlon KS, Mulinare J, Khoury MJ. Is maternal obesity a risk factor for anencephaly and spina bifida? Epidemiology 1996; 7:507-12. , 185185. Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA. Maternal obesity and risk for birth defects. Pediatrics 2003; 111:1152-8. , 186186. Werler MM, Sheehan JE, Mitchell AA. Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia. Epidemiology 2003; 14:349-54. , 187187. Werler MM, Starr JR, Cloonan YK, Speltz ML. Hemifacial microsomia: from gestation to childhood. J Craniofac Surg 2009; 20 Suppl 1:664-9. , 188188. Werler MM, Bosco JLF, Shapira SK. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects. Birth Defects Res A Clin Mol Teratol 2009; 85:52-7. , 189189. Werler MM, Mitchell AA, Moore CA, Honein MA. Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis? Am J Med Genet A 2009; 149A:1399-406. , 190190. Wong-Gibbons DL, Romitti PA, Sun L, Moore CA, Reefhuis J, Bell EM, et al. Maternal periconceptional exposure to cigarette smoking and alcohol and esophageal atresia tracheo-esophageal fistula. Birth Defects Res A Clin Mol Teratol 2008; 82:776-84. , 191191. Woods SE, Raju U. Maternal smoking and the risk of congenital birth defects: a cohort study. J Am Board Fam Pract 2001; 14:330-4. , 192192. Wyszynski DF, Wu T. Use of US birth certificate data to estimate the risk of maternal cigarette smoking for oral clefting. Cleft Palate Craniofac J 2002; 39:188-92. , 193193. Yerushalmy J. The relationship of parents' cigarette smoking to outcome of pregnancy - implications as to the problem of inferring causation from the observed associations. Am J Epidemiol 1971; 93:443-56. , 194194. Yerushalmy J. Congenital heart disease and maternal smoking habits. Nature 1973; 242:262-3. , 195195. Yuan P, Okazaki I, Kuroki Y. Anal atresia: effect of smoking and drinking habits during pregnancy. Jpn J Hum Genet 1995; 40:327-32. , 196196. Zeiger JS, Beaty TH, Hetmanski JB, Wang H, Scott AF, Kasch L, et al. Genetic and environmental risk factors for sagittal craniosynostosis. J Craniofac Surg 2002; 13:602-6. with a total of 13,564,914 subjects (192,655 birth defect cases, and 13,372,259 controls with no defects) were included in this review (Figure 2). Twenty-nine were prospective studies (cohort, or nested-case control studies), and 159 were retrospective (case-control, or cross-sectional studies). The overall characteristics of the 188 studies included are shown in Table 1.

Figure 2
Flowchart of the selection of studies included in the review.

Table 1
General characteristics of the studies included.

Table 2 presents individual and combined results of the 188 studies about the association between maternal smoking during pregnancy and birth defect of any type in children. The meta-analysis of the 188 studies showed that children of smoking mother had a higher chance of presenting any type of birth defects (OR: 1.18; 95%CI: 1.14-1.22; p < 0.001; I22. Powell-Griner E, Woolbright A. Trends in infant deaths from congenital anomalies: results from England and Wales, Scotland, Sweden and the United States. Int J Epidemiol 1990; 19:391-8.: 77.2%).

Table 2
Association between maternal smoking during pregnancy and birth defects in children: results of the 188 studies with birth defect of any type.

In the sub-group analyses, according to the organ systems involved, there were significant positive associations between maternal smoking and defects in the cardiovascular system (OR: 1.11; 95%CI: 1.03-1.19), digestive system (OR: 1.18; 95%CI: 1.07-1.30), musculoskeletal system (OR: 1.27; 95%CI: 1.16-139), and face and neck (OR: 1.28; 95%CI: 1.19-1.37) (Figure 3). Other subgroup analyses showed that retrospective studies and those with smaller sample size (≤ 1.000 cases) has higher combined OR values. Using or not adjustment/matching in the original studies to control confounding factors, particularly the age of the mother did not significantly affect the meta-analysis results (Table 3). Two post hocsub-group analyses were performed to assess the potential impact of the definition of maternal smoking, and the period of pregnancy the pregnant mother was exposed to smoking in the meta-analysis results. There was no statistically significant difference between studies in which maternal smoking during pregnancy was explicitly defined as daily smoking (n = 91; OR: 1.21; 95%CI: 1.16-1.26) and those studies with no clear definition (n = 97; OR: 1.17; 95%CI: 1.11-1.23) (χ2 = 1.0; p = 0.32). In addition, there was no statistically significant difference between studies in which exposure to smoking occurred in the first quarter of the pregnancy (n = 80; OR: 1.22; 95%CI: 1.17-1.29) and those studies with no clear definition (n = 108; OR: 1.16; 95%CI: 1.10-1.21) (χ2 = 2.1; p = 0.15).

Figure 3
Maternal smoking during pregnancy and birth defects in children according to the body systems involved. Note: weights are of random effect analysis. 95%CI: 95% confidence interval; ES: effect size; OR: odds ratio.

Table 3
Analysis of subgroups about the association between maternal smoking during pregnancy and birth defects in children.

Figure 4 shows the dose-response relation between maternal smoking during pregnancy and birth defects in children. Sixty studies 66. Bird TM, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51. , 77. Bracken MB, Holford TR, White C, Kelsey JL. Role of oral contraception in congenital malformations of offspring. Int J Epidemiol 1978; 7:309-17. , 88. Cedergren MI, Selbing AJ, Källén BAJ. Risk factors for cardiovascular malformation - a study based on prospectively collected data. Scan J Work Environ Health 2002; 28:12-7. , 99. Christensen K, Olsen J, Norgaard-Pedersen B, Basso O, Stovring H, Milhollin-Johnson L, et al. Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994. Am J Epidemiol 1999; 149:248-55. , 1111. Dickinson KC, Meyer RE, Kotch J. Maternal smoking and the risk for clubfoot in infants. Birth Defects Res A Clin Mol Teratol 2008; 82:86-91. , 1212. Feldkamp ML, Alder SC, Carey JC. A case control population-based study investigating smoking as a risk factor for gastroschisis in Utah, 1997-2005. Birth Defects Res A Clin Mol Teratol 2008; 82: 768-75. , 1616. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000; 283:2008-12. , 2121. Alderman BW, Bradley CM, Greene C, Fernbach SK, Baron AE. Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy. Teratology 1994; 50:13-8. , 2424. Bailey RR. The effect of maternal smoking on the infant birth weight. N Z Med J 1970; 71:293-4. , 3232. Bille C, Olsen J, Vach W, Knudsen VK, Olsen SF, Rasmussen K, et al. Oral clefts and life style factors: a case-cohort study based on prospective Danish data. Eur J Epidemiol 2007; 22:173-81. , 4343. Carmichael SL, Shaw GM, Laurent C, Lammer EJ, Olney RS. Hypospadias and maternal exposures to cigarette smoke. Pediatr Perinat Epidemiol 2005; 19:406-12. , 4444. Carmichael SL, Ma C, Rasmussen SA, Honein MA, Lammer EJ, Shaw GM. Craniosynostosis and maternal smoking. Birth Defects Res A Clin Mol Teratol 2008; 82:78-85. , 4747. Chevrier C, Bahuau M, Perret C, Iovannisci DM, Nelva A, Herman C, et al. Genetic susceptibilities in the association between maternal exposure to tobacco smoke and the risk of nonsyndromic oral cleft. Am J Med Genet A 2008; 146A:2396-406. , 4848. Chew E, Remaley NA, Tamboli A, Zhao J, Podgor MJ, Klebanoff M. Risk factors for esotropia and exotropia. Arch Ophthalmol 1994; 112:1349-55. , 4949. Christianson RE. The relationship between maternal smoking and the incidence of congenital anomalies. Am J Epidemiol 1980; 112:684-95. , 5151. Chung KC, Kowalski CP, Kim HM, Buchman SR. Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate. Plast Reconstr Surg 2000; 105:485-91. , 5757. Czeizel AE, Kodaj I, Lenz W. Smoking during pregnancy and congenital limb deficiency. BMJ 1994; 308:1473-6. , 5858. Czeizel AE, Petik D, Puho E. Smoking and alcohol drinking during pregnancy. The reliability of retrospective maternal self-reported information. Cent Eur J Public Health 2004; 12:179-83. , 6464. Ericson A, Kallen B, Westerholm P. Cigarette smoking as an etiologic factor in cleft lip and palate. Am J Obstet Gynecol 1979; 135:348-51. , 6565. Evans DR, Newcombe RG, Campbell H. Maternal smoking habits and congenital malformations: a population study. Br Med J 1979; 2:171-3. , 6969. Garcia AM, Fletcher T, Benavides FG, Orts E. Parental agricultural work and selected congenital malformations. Am J Epidemiol 1999; 149:64-74. , 7474. Hakim RB, Tielsch JM. Maternal cigarette smoking during pregnancy. A risk factor for childhood strabismus. Arch Ophthalmol 1992; 110:1459-62. , 8080. Honein MA, Paulozzi LJ, Moore CA. Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction. Am J Epidemiol 2000; 152:658-65. , 8282. Honein MA, Paulozzi LJ, Watkins ML. Maternal smoking and birth defects: validity of birth certificate data for effect estimation. Public Health Rep 2001; 116:327-35. , 8585. Jensen MS, Toft G, Thulstrup AM, Bonde JP, Olsen J. Cryptorchidism according to maternal gestational smoking. Epidemiology 2007; 18:220-5. , 8888. Kallen K. Maternal smoking and craniosynostosis. Teratology 1999; 60:146-50. , 8989. Kallen K. Multiple malformations and maternal smoking. Paediatr Perinat Epidemiol 2000; 14: 227-33. , 9090. Kelsey JL, Dwyer T, Holford TR, Bracken MB. Maternal smoking and congenital malformations: an epidemiological study. J Epidemiol Community Health 1978; 32:102-7. , 9191. Khoury MJ, Gomez-Farias M, Mulinare J. Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring? Am J Dis Child 1989; 143:333-7. , 9292. Krapels IP, Zielhuis GA, Vroom F, de Jong-van den Berg LT, Kuijpers-Jagtman AM, van der Molen AB, et al. Periconceptional health and lifestyle factors of both parents affect the risk of live-born children with orofacial clefts. Birth Defects Res A Clin Mol Teratol 2006; 76:613-20. , 9999. Lam PK, Torfs CP. Interaction between maternal smoking and malnutrition in infant risk of gastroschisis. Birth Defects Res A Clin Mol Teratol 2006; 76:182-6. , 100100. Leite IC, Koifman S. Oral clefts, consanguinity, parental tobacco and alcohol use: a case-control study in Rio de Janeiro, Brazil. Pesqui Odontol Bras 2009; 23:31-7. , 101101. Li DK, Mueller BA, Hickok DE, Daling JR, Fantel AG, Checkoway H, et al. Maternal smoking during pregnancy and the risk of congenital urinary tract anomalies. Am J Public Health 1996; 86: 249-53. , 103103. Lie RT, Wilcox AJ, Taylor J, Gjessing HK, Saugstad OD, Aabyholm F, et al. Maternal smoking and oral clefts. Epidemiology 2008; 19:606-15. , 104104. Lieff S, Olshan AF, Werler M, Strauss RP, Smith J, Mitchell A. Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns. Am J Epidemiol 1999; 150:683-94. , 107107. Liu S, Liu J, Tang J, Ji J, Chen J, Liu C. Environmental risk factors for congenital heart disease in the Shandong Peninsula, China: a hospital-based case-control study. J Epidemiol 2009; 19:122-30. , 108108. Lorente C, Cordier S, Goujard J, Aymé S, Bianchi F, Calzolari E, et al. Tobacco and alcohol use during pregnancy and risk of oral clefts. Am J Public Health 2000; 90:415-9. , 113113. Malik S, Cleves MA, Honein MA, Romitti PA, Botto LD, Yang S, et al. Maternal smoking and congenital heart defects. Pediatrics 2008; 121:e810-6. , 115115. Man LX, Chang B. Maternal cigarette smoking during pregnancy increases the risk of having a child with a congenital digital anomaly. Plast Reconst Surg 2006; 117:301-8. , 119119. McDonald AD, Armstrong BG, Sloan M. Cigarette, alcohol, and coffee consumption and congenital defects. Am J Public Health 1992; 82:91-3. , 121121. Miller EA, Manning SE, Rasmussen SA, Reefhuis J, Honein MA; National Birth Defects Prevention Study. Maternal exposure to tobacco smoke, alcohol and caffeine, and risk of anorectal atresia: National Birth Defects Prevention Study 1997-2003. Paediatr Perinat Epidemiol 2009; 23:9-17. , 122122. Miller EA, Rasmussen SA, Siega-Riz AM, Frías JL, Honein MA. Risk factors for non-syndromic holoprosencephaly in the national birth defects prevention study. Am J Med Genet C Semin Med Genet 2010; 154C:62-72. , 123123. Mitchell LE, Murray JC, O'Brien S, Christensen K. Evaluation of two putative susceptibility loci for oral clefts in the Danish population. Am J Epidemiol 2001; 153:1007-15. , 124124. Morales-Suárez-Varela MM, Bille C, Christensen K, Olsen J. Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol 2006; 107:51-7. , 132132. Oddsberg J, Jia C, Nilsson E, Ye W, Lagergren J. Maternal tobacco smoking, obesity, and low socioeconomic status during early pregnancy in the etiology of esophageal atresia. J Pediatr Surg 2008; 43:1791-5. , 135135. Parker SE, Mai CT, Strickland MJ, Olney RS, Rickard R, Marengo L, et al. Multistate study of the epidemiology of clubfoot. Birth Defects Res A Clin Mol Teratol 2009; 85:897-904. , 144144. Romitti PA, Sun L, Honein MA, Reefhuis J, Correa A, Rasmussen SA. Maternal periconceptional alcohol consumption and risk of orofacial clefts. Am J Epidemiol 2007; 166:775-85. , 150150. Shaw GM, Wasserman CR, Lammer EJ, O'Malley CD, Murray JC, Basart AM, et al. Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants. Am J Hum Genet 1996; 58:551-61. , 151151. Shaw GM, Velie EM, Morland KB. Parental recreational drug use and risk for neural tube defects. Am J Epidemiol 1996; 144:1155-60. , 157157. Slickers JE, Olshan AF, Siega-Riz AM, Honein MA, Aylsworth AS. Maternal body mass index and lifestyle exposures and the risk of bilateral renal agenesis or hypoplasia: the National Birth Defects Prevention Study. Am J Epidemiol 2008; 168:1259-67. , 163163. Suarez L, Felkner M, Brender JD, Canfield M, Hendricks K. Maternal exposures to cigarette smoke, alcohol, and street drugs and neural tube defect occurrence in offspring. Matern Child Health J 2008; 12:394-401. , 169169. Tikkanen J, Heinonen OP. Maternal exposure to chemical and physical factors during pregnancy and cardiovascular malformations in the offspring. Teratology 1991; 43:591-600. , 172172. Tornqvist K, Ericsson A, Kallen B. Optic nerve hypoplasia: risk factors and epidemiology. Acta Ophthalmol Scand 2002; 80:300-4. , 173173. Torp-Pedersen T, Boyd HA, Poulsen G, Haargaard B, Wohlfahrt J, Holmes JM, et al. In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus. Am J Epidemiol 2010; 171:868-75. , 187187. Werler MM, Starr JR, Cloonan YK, Speltz ML. Hemifacial microsomia: from gestation to childhood. J Craniofac Surg 2009; 20 Suppl 1:664-9. , 188188. Werler MM, Bosco JLF, Shapira SK. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects. Birth Defects Res A Clin Mol Teratol 2009; 85:52-7. , 189189. Werler MM, Mitchell AA, Moore CA, Honein MA. Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis? Am J Med Genet A 2009; 149A:1399-406. , 190190. Wong-Gibbons DL, Romitti PA, Sun L, Moore CA, Reefhuis J, Bell EM, et al. Maternal periconceptional exposure to cigarette smoking and alcohol and esophageal atresia tracheo-esophageal fistula. Birth Defects Res A Clin Mol Teratol 2008; 82:776-84. , 192192. Wyszynski DF, Wu T. Use of US birth certificate data to estimate the risk of maternal cigarette smoking for oral clefting. Cleft Palate Craniofac J 2002; 39:188-92. with a total of 12,137,944 subjects (103,107 cases) contributed their data to the analysis, of which 11 were prospective studies. The power of association between maternal smoking and defects measured by OR (95%CI) is significantly related with the daily amount of cigarettes smoked (χ² = 12.1; p = 0.002). Post hoc sub-group analyses were performed according to the design of the investigation, control of confounders, and size of the sample (cases). The statistically significant dose-response relation was seen in sub-groups of studies that had controlled confounder factors and in studies where the number of cases ranged between 200 and 5,000 (Table 4). The design of the investigation did not substantially affect the results of the dose-response relation.

Figure 4
Dose-response relation between maternal smoking and birth defects in children. Note: weights are of random effect analysis. Test for differences among sub-groups (χ2 = 12; df = 2; p = 0.002). 95%CI: 95% confidence interval; ES: effect size; OR: odds ratio.

Table 4
Post hoc subgroup analysis amout the dose-response relation between maternal smoking during pregnancy and birth defects in children.

The cumulative meta-analysis showed a statistically significant association between maternal smoking during pregnancy and birth defects in children when 40 studies published until 1990, with a total of 26,827 were included in the analysis (OR: 1.09; 95%CI: 1.001-1.19; p = 0.035). The OR (95%CI) and the p value were respectively 1.16 (1.10-1.23) and < 0.001, when 87 studies published until 2000, with a total of 95,556 cases were included in the meta-analysis. The result of the meta-analysis remained almost unchanged when 101 studies (97,099 cases) published between 2001 and 2010 were included (Figure 5).

Figure 5
Cumulative meta-analysis about the association between maternal smoking during pregnancy and birth defects in children. Note: weights are of random effect analysis. 95%CI: 95% confidence interval; ES: effect size; OR: odds ratio.

In the funnel plot (Figure 6), a slight asymmetry in the lower left corner was observed due to lack of studies, which suggested that studies with small samples demonstrating protective effects of maternal smoking against defects in children had not been published. The Egger test also showed evidence of the "small studies" effect, which suggests the presence of publication bias (p < 0.001).

Figure 6
Funnel plot.

Discussion

This systematic review with meta-analysis has shown that children of mothers who smoked during pregnancy are at a higher risk of presenting birth defects of any type. Significant associations between maternal smoking during pregnancy and birth defects of the cardiovascular, digestive, musculoskeletal systems and of the face and neck were evidenced. Positive associations were also observed between maternal smoking and birth defects of the respiratory, nervous, and urogenital systems; however, these associations were not statistically significant.

In this systematic review a statistically significant dose-response relation was alsou found between maternal smoking during pregnancy and the risk of birth defects in children; this means, the higher the number of cigarettes a day smoked by the mother, the higher the risk of having babies with some type of birth defects. It was also observed that all the three daily doses of cigarette-smoking were significantly associated with higher risk of birth defects compared to non-smoking, suggesting that the regular use of cigarettes by the pregnant woman, even in small amounts, may cause adverse impact in the development of the fetus.

The mechanisms of action of tobacco in the increase of abnormalities in babies are not accurately understood. It is believed that the vasoconstrictor effect of nicotine may reduce the uterine and placental blood flow197197. Leopércio W, Gigliotti A. Tabagismo e suas peculiaridades durante a gestação: uma revisão crítica. J Bras Pneumol 2004; 30:176-85.. Carbon monoxide binds to the hemoglobin in such a way that less oxygen is available for the placenta. In addition, the endothelial injury caused by tobacco increases the rupture of blood vessels from neovascularization of the placenta, leading to a decrease in the blood flow to the fetus, causing hypoxia which will likely result in abnormal fetal morphogenesis198198. Quinton AE, Cook CM, Peek MJ. The relationship between cigarette smoking, endothelial function and intrauterine growth restriction in human pregnancy. BJQG 2008; 115:780-4.. Therefore, exposure to toxins in tandem with hypoxia and cellular ischemia results in abnormal cellular proliferation.

Approximately one third of Brazilian adults were smokers by the end of the 1990s; there was, however, a reduction of about 50% (from 34% to 18.2%) in the prevalence of smokers in this population between 1989 and 2008199199. Szklo AS, de Almeida LM, Figueiredo VC, Autran M, Malta D, Caixeta R, et al. Snapshot of the striking decrease in cigarette smoking prevalence in Brazil between 1989 and 2008. Prev Med 2012; 54:162-7.. A number of factors account for this reduction, including anti-tobacco policies and availability of smoking-cessation treatments. Smoking during pregnancy is of particular concern, as it is associated with many maternal-fetal outcomes, such as low-weight at birth, premature deliveries, perinatal deaths, and birth defects200200. Salihu HM, Wilson RE. Epidemiology of parental smoking and perinatal outcomes. Early Hum Dev 2007; 83:713-20. , 201201. Zhang L, González-Chica DA, Cesar JA, Mendoza-Sassi RA, Beskow B, Larentis N, et al. Tabagismo materno durante a gestação e medidas antropométricas do recém-nascido: um estudo de base populacional no extremo sul do Brasil. Cad Saúde Pública 2011; 27:1768-76.. In countries such as the United States and Canada, where anti-tobacco governmental policies are aggressive, and strong investments are made to control smoking during pregnancy, the prevalence of maternal smoking during pregnancy is currently around 10 to 12% 202202. Tong VT, Dietz PM, Morrow B, D'Angelo DV, Farr SL, Rockhill KM, et al. Trends in smoking before, during, and after pregnancy: Pregnancy Risk Assessment Monitoring System, United States, 40 sites, 2000-2010. MMWR Surveill Summ 2013; 62:1-19. , 203203. Ontario Tobacco Research Unit. Indicators of smoke-free Ontario progress. Toronto: Ontario Tobacco Research Unit; 2010.. A recent study carried out in nine countries, including Latin America (Argentina, Brazil, Ecuador, Guatemala and Uruguay), Asia (India and Pakistan), and Africa (Democratic Republic of Congo and Zambia) showed higher prevalence of maternal smoking during pregnancy in Uruguay (18.3%), followed by Argentina (10.3%) and Brazil (6.1%) 204204. Bloch M, Althabe F, Onyamboko M, Kaseba-Sata C, Castilla EE, Freire S, et al. Tobacco use and secondhand smoke exposure during pregnancy: an investigative survey of women in 9 developing nations. Am J Public Health 2008; 98:1833-40. . However, some local studies made in Brazil have shown a prevalence of active smoking of around 20% among pregnant women 201201. Zhang L, González-Chica DA, Cesar JA, Mendoza-Sassi RA, Beskow B, Larentis N, et al. Tabagismo materno durante a gestação e medidas antropométricas do recém-nascido: um estudo de base populacional no extremo sul do Brasil. Cad Saúde Pública 2011; 27:1768-76. , 205205. Reis LG, da Silva CF, Trindade A, Abrahão M, da Silva VA. Quem são as mulheres tabagistas que param de fumar na gestação? Rev Bras Saúde Matern Infant 2008; 8:217-21. , a proportion much higher than the reported in this international multicentric study. These data point the need for yet stronger actions against tobacco-use during pregnancy in Latin America, including Brazil.

There are a number of resources available to facilitate smoking cessation, such as anti-smoking patches, and anti-anxiety agents like bupropion197197. Leopércio W, Gigliotti A. Tabagismo e suas peculiaridades durante a gestação: uma revisão crítica. J Bras Pneumol 2004; 30:176-85.. These may be used prior to the patient become pregnant. For this reason, we stress the importance of pre-pregnancy counseling.

A systematic review has also shown an association between maternal smoking during pregnancy and birth defects in children55. Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173687 malformed cases and 11.7 million controls. Hum Reprod Updat 2011; 17:589-604.. Compared to that review, this one has included 20 additional studies66. Bird TM, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51. , 77. Bracken MB, Holford TR, White C, Kelsey JL. Role of oral contraception in congenital malformations of offspring. Int J Epidemiol 1978; 7:309-17. , 88. Cedergren MI, Selbing AJ, Källén BAJ. Risk factors for cardiovascular malformation - a study based on prospectively collected data. Scan J Work Environ Health 2002; 28:12-7. , 99. Christensen K, Olsen J, Norgaard-Pedersen B, Basso O, Stovring H, Milhollin-Johnson L, et al. Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994. Am J Epidemiol 1999; 149:248-55. , 1010. DeRoo LA, Gaudino JA, Edmonds LD. Orofacial cleft malformations: associations with maternal and infant characteristics in Washington state. Birth Defects Res A Clin Mol Teratol 2003; 67: 637-42. , 1111. Dickinson KC, Meyer RE, Kotch J. Maternal smoking and the risk for clubfoot in infants. Birth Defects Res A Clin Mol Teratol 2008; 82:86-91. , 1212. Feldkamp ML, Alder SC, Carey JC. A case control population-based study investigating smoking as a risk factor for gastroschisis in Utah, 1997-2005. Birth Defects Res A Clin Mol Teratol 2008; 82: 768-75. , 1313. Ramirez D, Lammer EJ, Iovannisci DM, Laurent C, Finnell RH, Shaw GM. Maternal smoking during early pregnancy, GSTP1 and EPHX1 variants, and risk of isolated orofacial clefts. Cleft Palate Craniofac J 2007; 44:366-73. , 1414. Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors and risk for ventricular septal defects. Birth Defects Res A Clin Mol Teratol 2004; 70:59-64. , 2424. Bailey RR. The effect of maternal smoking on the infant birth weight. N Z Med J 1970; 71:293-4. , 4343. Carmichael SL, Shaw GM, Laurent C, Lammer EJ, Olney RS. Hypospadias and maternal exposures to cigarette smoke. Pediatr Perinat Epidemiol 2005; 19:406-12. , 7979. Hobbs CA, James SJ, Jernigan S, Melnyk S, Lu Y, Malik S, et al. Congenital heart defects, maternal homocysteine smoking, and the 677 C>T polymorphism in the methylenetetrahydroflate reductase gene: evaluating gene-environment interactions. Am J Obstet Gynecol 2006; 194:218-24. , 8383. Honein MA, Rasmussen SA, Reefhuis J, Romitti PA, Lammer EJ, Sun L, et al. Maternal smoking and environmental tobacco smoke exposure and the risk of orofacial clefts. Epidemiology 2007; 18:226-33. , 9595. Kuciene R, Dulskiene V. Maternal socioeconomic and lifestyle factors during pregnancy and the risk of congenital heart defects. Medicina (Kaunas) 2009; 45:904-9. , 9999. Lam PK, Torfs CP. Interaction between maternal smoking and malnutrition in infant risk of gastroschisis. Birth Defects Res A Clin Mol Teratol 2006; 76:182-6. , 102102. Li Z, Ren A, Zhang L, Guo Z, Li Z. A population-based case-control study of risk factors for neural tube defects in four high-prevalence areas of Shanxi province, China. Paediatr Perinat Epidemiol 2006; 20:43-53. , 103103. Lie RT, Wilcox AJ, Taylor J, Gjessing HK, Saugstad OD, Aabyholm F, et al. Maternal smoking and oral clefts. Epidemiology 2008; 19:606-15. , 122122. Miller EA, Rasmussen SA, Siega-Riz AM, Frías JL, Honein MA. Risk factors for non-syndromic holoprosencephaly in the national birth defects prevention study. Am J Med Genet C Semin Med Genet 2010; 154C:62-72. , 125125. Morgana LM, Cohn BA, Cohen RD, Christianson RE. Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies Cohort, 1959-1967. Am J Epidemiol 2008; 167:257-61. , 188188. Werler MM, Bosco JLF, Shapira SK. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects. Birth Defects Res A Clin Mol Teratol 2009; 85:52-7. that have added about 10,000 cases of defects, and 800,000 of controls. Another difference between the two reviews is that 19 studies about abdominal wall defects were included in the meta-analysis of the gastro-intestinal system in the previous review, whereas these defects were classified as pertaining to the musculoskeletal system in this review. Despite these methodological differences, the results of these two reviews were similar in regards to the association between maternal smoking during pregnancy and defects of the cardiovascular, respiratory, digestive, nervous, urogenital and musculoskeletal systems. The meta-analysis from the previous review included 38 studies in which all defects were combined together did not show significant association between maternal smoking and birth defects (OR: 1.01; 95%CI: 0.96-1.07). The meta-analysis of the current review has included all the 188 studies in which the defects were both combined or of a particular type, and evidenced a statistically significant association between maternal smoking during pregnancy and the risk of any type of birth defect in children (OR: 1.18; 95%CI: 1.14-1.22).

The cumulative meta-analysis of this current review shows that there was already evidence of the association between maternal smoking during pregnancy and birth defects in children by analyzing the results of 40 studies published until 1990 that included a total of 26,827 cases of defects (OR = 1.09; p = 0.035). The evidence of the association became more robust with the results of 87 studies published until 2000, with a total of 95,556 cases (OR = 1.16; p < 0.0001). Between 2000 and 2010, more than 100 studies were carried out with some 100,000 cases of defects; the inclusion of these studies, however, did not change significantly the results of the meta-analysis. These data indicate that findings about the association between maternal smoking during pregnancy and birth defects in children are convincing, and there is no need of further epidemiological studies to investigate this association.

Some methodological studies should be considered in interpreting the results of this systematic review. The heterogeneity of the results of the studies included in this review is to be expected, considering the differences in the research design, type of defect and method used for diagnosis, definition of maternal smoking and control of the effect of confounders. Some of the confounding factors were investigated through subgroup analyses, whose results suggest that the type of defect, the design of the research and the size of the sample are possible causes of heterogeneity. The quality of the studies included was not assessed individually due to limitations of the tools currently available206206. Sanderson S, Iain D, Tatt ID, Higgins JPT. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 2007; 36:666-76.; however, the potential influences of the methodological aspects of the studies (research design, sample size, control of the effect of confounders, and definition of exposure) in the results of the meta-analysis were investigated through the sub-group analyses. The influence of passive smoking in the association between maternal smoking during pregnancy and birth defects in children was not investigated due to lack of information in most of the original studies. Future studies should address this issue. The funnel plot and the Egger test suggest the presence of publication bias, due to non-publication of small studies that would demonstrate the protective effect of maternal smoking against defects in children. We believe that the number of this type of study is limited, and the lack of data from these studies does not significantly affect the results of the meta-analysis.

We conclude, from this systematic review with meta-analysis, that maternal smoking during pregnancy is associated with a higher risk of birth defects in children, and that this is a dose-dependent association.

References

  • 1
    Horovitz DDG, Llerena Jr. JC, Mattos RA. Atenção aos defeitos congênitos no Brasil: panorama atual. Cad Saúde Pública 2005; 21:1055-64.
  • 2
    Powell-Griner E, Woolbright A. Trends in infant deaths from congenital anomalies: results from England and Wales, Scotland, Sweden and the United States. Int J Epidemiol 1990; 19:391-8.
  • 3
    Neto PS, Zhang L, Nicoletti D, Munchen FB. Mortalidade infantil por malformações congênitas no Brasil. Rev AMRIGS 2012; 56:129-32.
  • 4
    Stillerman KP, Mattison DR, Giudice LC, Woodruff TJ. Environmental exposures and adverse pregnancy outcomes: a review of the science. Reprod Sci 2008; 15:631-50.
  • 5
    Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173687 malformed cases and 11.7 million controls. Hum Reprod Updat 2011; 17:589-604.
  • 6
    Bird TM, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51.
  • 7
    Bracken MB, Holford TR, White C, Kelsey JL. Role of oral contraception in congenital malformations of offspring. Int J Epidemiol 1978; 7:309-17.
  • 8
    Cedergren MI, Selbing AJ, Källén BAJ. Risk factors for cardiovascular malformation - a study based on prospectively collected data. Scan J Work Environ Health 2002; 28:12-7.
  • 9
    Christensen K, Olsen J, Norgaard-Pedersen B, Basso O, Stovring H, Milhollin-Johnson L, et al. Oral clefts, transforming growth factor alpha gene variants, and maternal smoking: a population-based case-control study in Denmark, 1991-1994. Am J Epidemiol 1999; 149:248-55.
  • 10
    DeRoo LA, Gaudino JA, Edmonds LD. Orofacial cleft malformations: associations with maternal and infant characteristics in Washington state. Birth Defects Res A Clin Mol Teratol 2003; 67: 637-42.
  • 11
    Dickinson KC, Meyer RE, Kotch J. Maternal smoking and the risk for clubfoot in infants. Birth Defects Res A Clin Mol Teratol 2008; 82:86-91.
  • 12
    Feldkamp ML, Alder SC, Carey JC. A case control population-based study investigating smoking as a risk factor for gastroschisis in Utah, 1997-2005. Birth Defects Res A Clin Mol Teratol 2008; 82: 768-75.
  • 13
    Ramirez D, Lammer EJ, Iovannisci DM, Laurent C, Finnell RH, Shaw GM. Maternal smoking during early pregnancy, GSTP1 and EPHX1 variants, and risk of isolated orofacial clefts. Cleft Palate Craniofac J 2007; 44:366-73.
  • 14
    Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors and risk for ventricular septal defects. Birth Defects Res A Clin Mol Teratol 2004; 70:59-64.
  • 15
    Centro Colaborador da OMS para a Classificação de Doenças em Português. Classificação estatística internacional de doenças e problemas relacionados à saúde. 10a revisão. http://www.datasus.gov.br/cid10/V2008/cid10.htm (accessed on 20/Apr/2010).
    » http://www.datasus.gov.br/cid10/V2008/cid10.htm
  • 16
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000; 283:2008-12.
  • 17
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analysis. BMJ 2003; 327:557-60.
  • 18
    Adams MM, Mulinare J, Dooley K. Risk factors for conotruncal cardiac defects in Atlanta. J Am Coll Cardiol 1989; 14:432-42.
  • 19
    Akre O, Lipworth L, Cnattingius S, Sparen P, Ekbom A. Risk factor patterns for cryptorchidism and hypospadias. Epidemiology 1999; 10:364-9.
  • 20
    Alderman BW, Takahashi ER, LeMier MK. Risk indicators for talipes equinovarus in Washington State, 1987-1989. Epidemiology 1991; 2:289-92.
  • 21
    Alderman BW, Bradley CM, Greene C, Fernbach SK, Baron AE. Increased risk of craniosynostosis with maternal cigarette smoking during pregnancy. Teratology 1994; 50:13-8.
  • 22
    Ananijevic-Pandey J, Jarebinski M, Kastratovic B, Vlajinac H, Radojkovic Z, Brankovic D. Case-control study of congenital malformations. Eur J Epidemiol 1992; 8:871-4.
  • 23
    Aro T. Maternal diseases, alcohol consumption and smoking during pregnancy associated with reduction limb defects. Early Hum Dev 1983; 9: 49-57.
  • 24
    Bailey RR. The effect of maternal smoking on the infant birth weight. N Z Med J 1970; 71:293-4.
  • 25
    Batra M, Heike CL, Phillips RC, Weiss NS. Geographic and occupational risk factors for ventricular septal defects: Washington State, 1987-2003. Arch Pediatr Adolesc Med 2007; 161:89-95.
  • 26
    Beard CM, Melton LJ, O'Fallon WM, Noller KL, Benson RC. Cryptorchism and maternal estrogen exposure. Am J Epidemiol 1984; 120:707-16.
  • 27
    Beaty TH, Maestri NE, Hetmanski JB, Wyszynski DF, Vanderkolk CA, Simpson JC, et al. Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992-1996. Cleft Palate Craniofac J 1997; 34: 447-54.
  • 28
    Beaty TH, Wang H, Hetmanski JB, Fan YT, Zeiger JS, Liang KY, et al. A case-control study of nonsyndromic oral clefts in Maryland. Ann Epidemiol 2001; 11:434-42.
  • 29
    Bell R, Lumley J. Alcohol consumption, cigarette smoking and fetal outcome in Victoria, 1985. Community Health Stud 1989; 13:484-91.
  • 30
    Berkowitz GS, Lapinski RH. Risk factors for cryptorchidism: a nested case-control study. Paediatr Perinat Epidemiol 1996; 10:39-51.
  • 31
    Biggs ML, Baer A, Critchlow CW. Maternal, delivery, and perinatal characteristics associated with cryptorchidism: a population-based case-control study among births in Washington State. Epidemiology 2002; 13:197-204.
  • 32
    Bille C, Olsen J, Vach W, Knudsen VK, Olsen SF, Rasmussen K, et al. Oral clefts and life style factors: a case-cohort study based on prospective Danish data. Eur J Epidemiol 2007; 22:173-81.
  • 33
    Bitsko RH, Reefhuis J, Romitti PA, Moore CA, Honein MA. Periconceptional consumption of vitamins containing folic acid and risk for multiple congenital anomalies. Am J Med Genet A 2007; 143A:2397-405.
  • 34
    Blatter BM, Roeleveld N, Zielhuis GA, Gabreels FJ, Verbeek AL. Maternal occupational exposure during pregnancy and the risk of spina bifida. Occup Environ Med 1996; 53:80-6.
  • 35
    Botto LD, Lynberg MC, Erickson JD. Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study. Epidemiology 2001; 12:485-90.
  • 36
    Brouwers MM, Feitz WF, Roelofs LA, Kiemeney LA, de Gier RP, Roeleveld N. Risk factors for hypospadias. Eur J Pediatr 2007; 166:671-8.
  • 37
    Brouwers MM, van der Zanden LF, de Gier RP, Barten EJ, Zielhuis GA, Feitz WF, et al. Hypospadias: risk factor patterns and different phenotypes. BJU Int. 2010; 105:254-62.
  • 38
    Browne ML, Bell EM, Druschel CM, Gensburg LJ, Mitchell AA, Lin AE, et al. Maternal caffeine consuption and risk of cardiovascular malformations. Birth Defects Res A Clin Mol Teratol 2007; 79: 533-43.
  • 39
    Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, et al. The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. Int J Androl 2007; 30:3-13.
  • 40
    Cardy AH, Barker S, Chesney D, Sharp L, Maffulli N, Miedzybrodzka Z. Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study. BMC Musculoskelet Disord 2007; 8:62.
  • 41
    Carmichael SL, Shaw GM. Maternal life event stress and congenital anomalies. Epidemiology 2000; 11:30-5.
  • 42
    Carmichael SL, Nelson V, Shaw GM, Wasserman CR, Croen LA. Socio-economic status and risk of conotruncal heart defects and orofacial clefts. Paediatr Perinat Epidemiol 2003; 17:264-71.
  • 43
    Carmichael SL, Shaw GM, Laurent C, Lammer EJ, Olney RS. Hypospadias and maternal exposures to cigarette smoke. Pediatr Perinat Epidemiol 2005; 19:406-12.
  • 44
    Carmichael SL, Ma C, Rasmussen SA, Honein MA, Lammer EJ, Shaw GM. Craniosynostosis and maternal smoking. Birth Defects Res A Clin Mol Teratol 2008; 82:78-85.
  • 45
    Caton AR, Bell EM, Druschel CM, Werler MM, Mitchell AA, Browne ML, et al. Maternal hypertension, antihypertensive medication use, and the risk of severe hypospadias. Birth Defects Res A Clin Mol Teratol 2008; 82:34-40.
  • 46
    Chambers CD, Chen BH, Kalla K, Jernigan L, Jones KL. Novel risk factor in gastroschisis: change of paternity. Am J Med Genet A 2007; 143A:653-9.
  • 47
    Chevrier C, Bahuau M, Perret C, Iovannisci DM, Nelva A, Herman C, et al. Genetic susceptibilities in the association between maternal exposure to tobacco smoke and the risk of nonsyndromic oral cleft. Am J Med Genet A 2008; 146A:2396-406.
  • 48
    Chew E, Remaley NA, Tamboli A, Zhao J, Podgor MJ, Klebanoff M. Risk factors for esotropia and exotropia. Arch Ophthalmol 1994; 112:1349-55.
  • 49
    Christianson RE. The relationship between maternal smoking and the incidence of congenital anomalies. Am J Epidemiol 1980; 112:684-95.
  • 50
    Chung CS, Myrianthopoulos NC. Factors affecting risks of congenital malformations. I. Analysis of epidemiologic factors in congenital malformations. Report from the Collaborative Perinatal Project. Birth Defects Orig Artic Ser 1975; 11:1-22.
  • 51
    Chung KC, Kowalski CP, Kim HM, Buchman SR. Maternal cigarette smoking during pregnancy and the risk of having a child with cleft lip/palate. Plast Reconstr Surg 2000; 105:485-91.
  • 52
    Cordier S, Ha MC, Ayme S, Goujard J. Maternal occupational exposure and congenital malformations. Scand J Work Environ Health 1992; 18:11-7.
  • 53
    Correy JF, Newman NM, Collins JA, Burrows EA, Burrows RF, Curran JT. Use of prescription drugs in the first trimester and congenital malformations. Aust N Z J Obstet Gynaecol 1991; 31:340-4.
  • 54
    Croen LA, Shaw GM, Lammer EJ. Risk factors for cytogenetically normal holoprosencephaly in California: a population-based case-control study. Am J Med Genet 2000; 90:320-5.
  • 55
    Czeizel A, Vitez M. Etiological study of omphalocele. Hum Genet 1981; 58:390-5.
  • 56
    Czeizel A, Nagy E. A recent aetiological study on facial clefting in Hungary. Acta Paediatr Hung 1986; 27:145-66.
  • 57
    Czeizel AE, Kodaj I, Lenz W. Smoking during pregnancy and congenital limb deficiency. BMJ 1994; 308:1473-6.
  • 58
    Czeizel AE, Petik D, Puho E. Smoking and alcohol drinking during pregnancy. The reliability of retrospective maternal self-reported information. Cent Eur J Public Health 2004; 12:179-83.
  • 59
    Costa CMS, Gama SGN, Leal MC. Congenital malformations in Rio de Janeiro, Brazil: prevalence and associated factors. Cad Saúde Pública 2006; 22:2423-31.
  • 60
    Damgaard IN, Jensen TK; Nordic Cryptorchidism Study Group; Petersen JH, Skakkebaek NE, Toppari J, et al. Risk factors for congenital cryptorchidism in a prospective birth cohort study. PLoS One 2008; 3:e3051.
  • 61
    Davies TW, Williams DR, Whitaker RH. Risk factors for undescended testis. Int J Epidemiol 1986; 15:197-201.
  • 62
    Draper ES, Rankin J, Tonks A, Boyd P, Wellesley D, Tucker D, et al. Recreational drug use: a major risk factor for gastroschisis? Am J Epidemiol 2008; 167:485-91.
  • 63
    Erickson JD. Risk factors for birth defects: data from the Atlanta Birth Defects Case-Control Study. Teratology 1991; 43:41-51.
  • 64
    Ericson A, Kallen B, Westerholm P. Cigarette smoking as an etiologic factor in cleft lip and palate. Am J Obstet Gynecol 1979; 135:348-51.
  • 65
    Evans DR, Newcombe RG, Campbell H. Maternal smoking habits and congenital malformations: a population study. Br Med J 1979; 2:171-3.
  • 66
    Fedrick J, Alberman ED, Goldstein H. Possible teratogenic effect of cigarette smoking. Nature 1971; 231:529-30.
  • 67
    Felix JF, van Dooren MF, Klaassens M, Hop WC, Torfs CP, Tibboel D. Environmental factors in the etiology of esophageal atresia and congenital diaphragmatic hernia: results of a case-control study. Birth Defects Res A Clin Mol Teratol 2008; 82: 98-105.
  • 68. Ferencz C, Loffredo CA, Correa-Villasenor A. Genetic and environmental risk factors of major cardiovascular malformations: The Baltimore-Washington Infant Study 1981-1989. Armonk: Futura Publishing Co.; 1997.
  • 69
    Garcia AM, Fletcher T, Benavides FG, Orts E. Parental agricultural work and selected congenital malformations. Am J Epidemiol 1999; 149:64-74.
  • 70
    Goldbaum G, Daling J, Milham S. Risk factors for gastroschisis. Teratology 1990; 42:397-403.
  • 71
    Golding J, Butler NR. Maternal smoking and anencephaly. Br Med J (Clin Res Ed) 1983; 287:533-4.
  • 72
    Grewal J, Carmichael SL, Ma C, Lammer EJ, Shaw GM. Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies. Birth Defects Res A Clin Mol Teratol 2008; 82:519-26.
  • 73
    Haddow JE, Palomaki GE, Holman MS. Young maternal age and smoking during pregnancy as risk factors for gastroschisis. Teratology 1993; 47:225-8.
  • 74
    Hakim RB, Tielsch JM. Maternal cigarette smoking during pregnancy. A risk factor for childhood strabismus. Arch Ophthalmol 1992; 110:1459-62.
  • 75
    Hearey CD, Harris JA, Usatin MS, Epstein DM, Ury HK, Neutra RR. Investigation of a cluster of anencephaly and spina bifida. Am J Epidemiol 1984; 120:559-64.
  • 76. Heinonen OP. Birth defects and drugs in pregnancy. Littleton: Publishing Sciences Group, Inc.; 1977.
  • 77
    Hemminki K, Mutanen P, Saloniemi I, Luoma K. Congenital malformations and maternal occupation in Finland: multivariate analysis. J Epidemiol Community Health 1981; 35:5-10.
  • 78
    Himmelberger DU, Brown Jr. BW, Cohen EN. Cigarette smoking during pregnancy and the occurrence of spontaneous abortion and congenital abnormality. Am J Epidemiol 1978; 108:470-9.
  • 79
    Hobbs CA, James SJ, Jernigan S, Melnyk S, Lu Y, Malik S, et al. Congenital heart defects, maternal homocysteine smoking, and the 677 C>T polymorphism in the methylenetetrahydroflate reductase gene: evaluating gene-environment interactions. Am J Obstet Gynecol 2006; 194:218-24.
  • 80
    Honein MA, Paulozzi LJ, Moore CA. Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction. Am J Epidemiol 2000; 152:658-65.
  • 81
    Honein MA, Rasmussen SA. Further evidence for an association between maternal smoking and craniosynostosis. Teratology 2000; 62:145-6.
  • 82
    Honein MA, Paulozzi LJ, Watkins ML. Maternal smoking and birth defects: validity of birth certificate data for effect estimation. Public Health Rep 2001; 116:327-35.
  • 83
    Honein MA, Rasmussen SA, Reefhuis J, Romitti PA, Lammer EJ, Sun L, et al. Maternal smoking and environmental tobacco smoke exposure and the risk of orofacial clefts. Epidemiology 2007; 18:226-33.
  • 84
    Hougland KT, Hanna AM, Meyers R, Null D. Increasing prevalence of gastroschisis in Utah. J Pediatr Surg 2005; 40:535-40.
  • 85
    Jensen MS, Toft G, Thulstrup AM, Bonde JP, Olsen J. Cryptorchidism according to maternal gestational smoking. Epidemiology 2007; 18:220-5.
  • 86
    Johansen AM, Wilcox AJ, Lie RT, Andersen LF, Drevon CA. Maternal consumption of coffee and caffeine-containing beverages and oral clefts: a population-based case-control study in Norway. Am J Epidemiol 2009; 169:1216-22.
  • 87
    Jones ME, Swerdlow AJ, Griffith M, Goldacre MJ. Prenatal risk factors for cryptorchidism: a record linkage study. Paediatr Perinat Epidemiol 1998; 12:383-96.
  • 88
    Kallen K. Maternal smoking and craniosynostosis. Teratology 1999; 60:146-50.
  • 89
    Kallen K. Multiple malformations and maternal smoking. Paediatr Perinat Epidemiol 2000; 14: 227-33.
  • 90
    Kelsey JL, Dwyer T, Holford TR, Bracken MB. Maternal smoking and congenital malformations: an epidemiological study. J Epidemiol Community Health 1978; 32:102-7.
  • 91
    Khoury MJ, Gomez-Farias M, Mulinare J. Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring? Am J Dis Child 1989; 143:333-7.
  • 92
    Krapels IP, Zielhuis GA, Vroom F, de Jong-van den Berg LT, Kuijpers-Jagtman AM, van der Molen AB, et al. Periconceptional health and lifestyle factors of both parents affect the risk of live-born children with orofacial clefts. Birth Defects Res A Clin Mol Teratol 2006; 76:613-20.
  • 93
    Krauss MJ, Morrissey AE, Winn HN, Amon E, Leet TL. Microcephaly: an epidemiologic analysis. Am J Obstet Gynecol 2003; 188:1484-9.
  • 94
    Kricker A, Elliott JW, Forrest JM, McCredie J. Congenital limb reduction deformities and use of oral contraceptives. Am J Obstet Gynecol 1986; 155:1072-8.
  • 95
    Kuciene R, Dulskiene V. Maternal socioeconomic and lifestyle factors during pregnancy and the risk of congenital heart defects. Medicina (Kaunas) 2009; 45:904-9.
  • 96
    Kullander S, Kallen B. A prospective study of smoking and pregnancy. Acta Obstet Gynecol Scand 1971; 50:83-94.
  • 97
    Kurahashi N, Kasai S, Shibata T, Kakizaki H, Nonomura K, Sata F, et al. Parental and neonatal risk factors for cryptorchidism. Med Sci Monit 2005; 11:CR274-83.
  • 98
    Kurahashi N, Sata F, Kasai S, Shibata T, Moriya K, Yamada H, et al. Maternal genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 and the risk of hypospadias. Mol Hum Reprod 2005; 11:93-8.
  • 99
    Lam PK, Torfs CP. Interaction between maternal smoking and malnutrition in infant risk of gastroschisis. Birth Defects Res A Clin Mol Teratol 2006; 76:182-6.
  • 100
    Leite IC, Koifman S. Oral clefts, consanguinity, parental tobacco and alcohol use: a case-control study in Rio de Janeiro, Brazil. Pesqui Odontol Bras 2009; 23:31-7.
  • 101
    Li DK, Mueller BA, Hickok DE, Daling JR, Fantel AG, Checkoway H, et al. Maternal smoking during pregnancy and the risk of congenital urinary tract anomalies. Am J Public Health 1996; 86: 249-53.
  • 102
    Li Z, Ren A, Zhang L, Guo Z, Li Z. A population-based case-control study of risk factors for neural tube defects in four high-prevalence areas of Shanxi province, China. Paediatr Perinat Epidemiol 2006; 20:43-53.
  • 103
    Lie RT, Wilcox AJ, Taylor J, Gjessing HK, Saugstad OD, Aabyholm F, et al. Maternal smoking and oral clefts. Epidemiology 2008; 19:606-15.
  • 104
    Lieff S, Olshan AF, Werler M, Strauss RP, Smith J, Mitchell A. Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns. Am J Epidemiol 1999; 150:683-94.
  • 105
    Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ryan KJ. Lack of association between contraceptive usage and congenital malformations in offspring. Am J Obstet Gynecol 1983; 147:923-8.
  • 106
    Little J, Cardy A, Arslan MT, Gilmour M, Mossey PA. Smoking and orofacial clefts: a United Kingdom-based case-control study. Cleft Palate Craniofac J 2004; 41:381-6.
  • 107
    Liu S, Liu J, Tang J, Ji J, Chen J, Liu C. Environmental risk factors for congenital heart disease in the Shandong Peninsula, China: a hospital-based case-control study. J Epidemiol 2009; 19:122-30.
  • 108
    Lorente C, Cordier S, Goujard J, Aymé S, Bianchi F, Calzolari E, et al. Tobacco and alcohol use during pregnancy and risk of oral clefts. Am J Public Health 2000; 90:415-9.
  • 109
    Lowe CR. Effect of mothers' smoking habits on birth weight of their children. Br Med J 1959; 2:673-6.
  • 110
    Lubs ML. Racial differences in maternal smoking effects on the newborn infant. Am J Obstet Gynecol 1973; 115:66-76.
  • 111
    Lumley J, Correy JF, Newman NM, Curran JT. Cigarette smoking, alcohol consumption and fetal outcome in Tasmania 1981-82. Aust N Z J Obstet Gynaecol 1985; 25:33-40.
  • 112
    MacBird T, Robbins JM, Druschel C, Cleves MA, Yang S, Hobbs CA. Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study. J Pediatr Surg 2009; 44:1546-51.
  • 113
    Malik S, Cleves MA, Honein MA, Romitti PA, Botto LD, Yang S, et al. Maternal smoking and congenital heart defects. Pediatrics 2008; 121:e810-6.
  • 114
    Malloy MH, Kleinman JC, Bakewell JM, Schramm WF, Land GH. Maternal smoking during pregnancy: no association with congenital malformations in Missouri 1980-83. Am J Public Health 1989; 79:1243-6.
  • 115
    Man LX, Chang B. Maternal cigarette smoking during pregnancy increases the risk of having a child with a congenital digital anomaly. Plast Reconst Surg 2006; 117:301-8.
  • 116
    Mandiracioglu A, Ulman I, Luleci E, Ulman C. The incidence and risk factors of neural tube defects in Izmir, Turkey: a nested case-control study. Turk J Pediatr 2004; 46:214-20.
  • 117
    Martinez-Frias ML, Rodriguez-Pinilla E, Prieto L. Prenatal exposure to salicylates and gastroschisis: a case-control study. Teratology 1997; 56: 241-3.
  • 118
    McBride ML, van den Steen N, Lamb CW, Gallagher RP. Maternal and gestational factors in cryptorchidism. Int J Epidemiol 1991; 20:964-70.
  • 119
    McDonald AD, Armstrong BG, Sloan M. Cigarette, alcohol, and coffee consumption and congenital defects. Am J Public Health 1992; 82:91-3.
  • 120
    McGlynn KA, Graubard BI, Klebanoff MA, Longnecker MP. Risk factors for cryptorchism among populations at differing risks of testicular cancer. Int J Epidemiol 2006; 35:787-95.
  • 121
    Miller EA, Manning SE, Rasmussen SA, Reefhuis J, Honein MA; National Birth Defects Prevention Study. Maternal exposure to tobacco smoke, alcohol and caffeine, and risk of anorectal atresia: National Birth Defects Prevention Study 1997-2003. Paediatr Perinat Epidemiol 2009; 23:9-17.
  • 122
    Miller EA, Rasmussen SA, Siega-Riz AM, Frías JL, Honein MA. Risk factors for non-syndromic holoprosencephaly in the national birth defects prevention study. Am J Med Genet C Semin Med Genet 2010; 154C:62-72.
  • 123
    Mitchell LE, Murray JC, O'Brien S, Christensen K. Evaluation of two putative susceptibility loci for oral clefts in the Danish population. Am J Epidemiol 2001; 153:1007-15.
  • 124
    Morales-Suárez-Varela MM, Bille C, Christensen K, Olsen J. Smoking habits, nicotine use, and congenital malformations. Obstet Gynecol 2006; 107:51-7.
  • 125
    Morgana LM, Cohn BA, Cohen RD, Christianson RE. Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies Cohort, 1959-1967. Am J Epidemiol 2008; 167:257-61.
  • 126
    Mori M, Davies TW, Tsukamoto T, Kumamoto Y, Fukuda K. Maternal and other factors of cryptorchidism: a case-control study in Japan. Kurume Med J 1992; 39:53-60.
  • 127
    Mossey PA, Davies JA, Little J. Prevention of orofacial clefts: does pregnancy planning have a role? Cleft Palate Craniofac J 2007; 44:244-50.
  • 128
    Munoz JB, Lacasana M, Aburto VHB, Sanchez LET, Garcia AMG, Carrillo LL. Socioeconomic factors and the risk of anencephaly in a Mexican population: a case-control study. Public Health Rep 2005; 120:39-45.
  • 129
    Mygind H, Thulstrup AM, Pedersen L, Larsen H. Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy. Acta Obstet Gynecol Scand 2002; 81:234-9.
  • 130
    Niebyl JR, Blake DA, Rocco LE, Baumgardner R, Mellits ED. Lack of maternal metabolic, endocrine, and environmental influences in the etiology of cleft lip with or without cleft palate. Cleft Palate J 1985; 22:20-8.
  • 131
    Nørgaard M, Wogelius P, Pedersen L, Rothman KJ, Sørensen HT. Maternal use of oral contraceptives during early pregnancy and risk of hypospadias in male offspring. Urology 2009; 74:583-7.
  • 132
    Oddsberg J, Jia C, Nilsson E, Ye W, Lagergren J. Maternal tobacco smoking, obesity, and low socioeconomic status during early pregnancy in the etiology of esophageal atresia. J Pediatr Surg 2008; 43:1791-5.
  • 133
    Ormond G, Nieuwenhuijsen MJ, Nelson P, Toledano MB, Iszatt N, Geneletti S, et al. Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ Health Perspect 2009; 117:303-7.
  • 134. Parikh CR, McCall D, Engelman C, Schrier RW. Congenital renal agenesis: case-control analysis of birth characteristics. Am J Kidney Dis 2002 39:689-94.
  • 135
    Parker SE, Mai CT, Strickland MJ, Olney RS, Rickard R, Marengo L, et al. Multistate study of the epidemiology of clubfoot. Birth Defects Res A Clin Mol Teratol 2009; 85:897-904.
  • 136
    Pierik FH, Burdorf A, Deddens JA, Juttmann RE, Weber RF. Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Environ Health Perspect 2004; 112:1570-6.
  • 137
    Porter MP, Faizan MK, Grady RW, Mueller BA. Hypospadias in Washington State: maternal risk factors and prevalence trends. Pediatrics 2005; 115:e495-9.
  • 138
    Preiksa RT, Zilaitiene B, Matulevicius V, Skakkebaek NE, Petersen JH, Jorgensen N, et al. Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod 2005; 20:1928-32.
  • 139
    Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J. Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998). Arch Gynecol Obstet 2002; 266: 163-7.
  • 140
    Rantakallio P. Relationship of maternal smoking to morbidity and mortality of the child up to the age of five. Acta Paediatr Scand 1978; 67:621-31.
  • 141
    Reefhuis J, de Walle HE, Cornel MC. Maternal smoking and deformities of the foot: results of the EUROCAT Study. European Registries of Congenital Anomalies. Am J Public Health 1998; 88:1554-5.
  • 142
    Robitaille J, Carmichael SL, Shaw GM, Olney RS; National Birth Defects Prevention Study. Maternal nutrient intake and risks for transverse and longitudinal limb deficiencies: data from the National Birth Defects Prevention Study, 1997-2003. Birth Defects Res A Clin Mol Teratol 2009; 85: 773-9.
  • 143
    Rodríguez-Pinilla E, Mejías C, Prieto-Merino D, Fernández P, Martínez-Frias ML; ECEMC Working Group. Risk of hypospadias in newborn infants exposed to valproic acid during the first trimester of pregnancy: a case-control study in Spain. Drug Saf 2008; 31:537-43.
  • 144
    Romitti PA, Sun L, Honein MA, Reefhuis J, Correa A, Rasmussen SA. Maternal periconceptional alcohol consumption and risk of orofacial clefts. Am J Epidemiol 2007; 166:775-85.
  • 145
    Salemi JL, Pierre M, Tanner JP, Kornosky JL, Hauser KW, Kirby RS, et al. Maternal nativity as a risk factor for gastroschisis: a population-based study. Birth Defects Res A Clin Mol Teratol 2009; 85:890-6.
  • 146
    Saxen I. Cleft lip and palate in Finland: parental histories, course of pregnancy and selected environmental factors. Int J Epidemiol 1974; 3: 263-70.
  • 147
    Schmidt RJ, Romitti PA, Burns TL, Browne ML, Druschel CM, Olney RS. Maternal caffeine consumption and risk of neural tube defects. Birth Defects Res A Clin Mol Teratol 2009; 85:879-89.
  • 148
    Seidman DS, Ever-Hadani P, Gale R. Effect of maternal smoking and age on congenital anomalies. Obstet Gynecol 1990; 76:1046-50.
  • 149
    Shaw GM, Malcoe LH, Swan SH, Cummins SK, Schulman J. Congenital cardiac anomalies relative to selected maternal exposures and conditions during early pregnancy. Eur J Epidemiol 1992; 8:757-60.
  • 150
    Shaw GM, Wasserman CR, Lammer EJ, O'Malley CD, Murray JC, Basart AM, et al. Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants. Am J Hum Genet 1996; 58:551-61.
  • 151
    Shaw GM, Velie EM, Morland KB. Parental recreational drug use and risk for neural tube defects. Am J Epidemiol 1996; 144:1155-60.
  • 152
    Shaw GM, Wasserman CR, O'Malley CD, Nelson V, Jackson RJ. Maternal pesticide exposure from multiple sources and selected congenital anomalies. Epidemiology 1999; 10:60-6.
  • 153
    Shaw GM, Croen LA, Todoroff K, Tolarova MM. Periconceptional intake of vitamin supplements and risk of multiple congenital anomalies. Am J Med Genet 2000; 93:188-93.
  • 154
    Shi M, Christensen K, Weinberg CR, Romitti P, Bathum L, Lozada A, et al. Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants. Am J Hum Genet 2007; 80:76-90.
  • 155
    Shiono PH, Klebanoff MA, Berendes HW. Congenital malformations and maternal smoking during pregnancy. Teratology 1986; 34:65-71.
  • 156
    Skelly AC, Holt VL, Mosca VS, Alderman BW. Talipes equinovarus and maternal smoking: a population-based case-control study in Washington state. Teratology 2002; 66:91-100.
  • 157
    Slickers JE, Olshan AF, Siega-Riz AM, Honein MA, Aylsworth AS. Maternal body mass index and lifestyle exposures and the risk of bilateral renal agenesis or hypoplasia: the National Birth Defects Prevention Study. Am J Epidemiol 2008; 168:1259-67.
  • 158
    Smedts HP, de Vries JH, Rakhshandehroo M, Wildhagen MF, Verkleij-Hagoort AC, Steegers EA, et al. High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring. BJOG 2009; 116:416-23.
  • 159
    Sorensen HT, Norgard B, Pedersen L, Larsen H, Johnsen SP. Maternal smoking and risk of hypertrophic infantile pyloric stenosis: 10 year population based cohort study. BMJ 2002; 325:1011-2.
  • 160
    Steinberger EK, Ferencz C, Loffredo CA. Infants with single ventricle: a population-based epidemiological study. Teratology 2002; 65:106-15.
  • 161
    Stoll C, Alembik Y, Roth MP, Dott B. Risk factors in congenital anal atresias. Ann Genet 1997; 40: 197-204.
  • 162
    Stoll C, Alembik Y, Dott B, Roth MP. Risk factors in congenital abdominal wall defects (omphalocele and gastroschisi): a study in a series of 265,858 consecutive births. Ann Genet 2001; 44:201-8.
  • 163
    Suarez L, Felkner M, Brender JD, Canfield M, Hendricks K. Maternal exposures to cigarette smoke, alcohol, and street drugs and neural tube defect occurrence in offspring. Matern Child Health J 2008; 12:394-401.
  • 164
    Szendrey T, Danyi G, Czeizel A. Etiological study on isolated esophageal atresia. Hum Genet 1985; 70:51-8.
  • 165
    Tamura T, Munger RG, Corcoran C, Bacayao JY, Nepomuceno B, Solon F. Plasma zinc concentrations of mothers and the risk of nonsyndromic oral clefts in their children: a case-control study in the Philippines. Birth Defects Res A Clin Mol Teratol 2005; 73:612-6.
  • 166
    Targett CS, Ratten GJ, Abell DA, Beischer NA. The influence of smoking on intrauterine fetal growth and on maternal oestriol excretion. Aust N Z J Obstet Gynecol 1977; 17:126-30.
  • 167
    Tata LJ, Lewis SA, McKeever TM, Smith CJ, Doyle P, Smeeth L, et al. Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study. Thorax 2008; 63:981-7.
  • 168
    The NS, Honein MA, Caton AR, Moore CA, Siega-Riz AM, Druschel CM. Risk factors for isolated biliary atresia, National Birth Defects Prevention Study, 1997-2002. Am J Med Genet A 2007; 143A:2274-84.
  • 169
    Tikkanen J, Heinonen OP. Maternal exposure to chemical and physical factors during pregnancy and cardiovascular malformations in the offspring. Teratology 1991; 43:591-600.
  • 170
    To WW, Tang MH. The association between maternal smoking and fetal hydranencephaly. J Obstet Gynaecol Res 1999; 25:39-42.
  • 171
    Torfs CP, Velie EM, Oechsli FW, Bateson TF, Curry CJ. A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 1994; 50:44-53.
  • 172
    Tornqvist K, Ericsson A, Kallen B. Optic nerve hypoplasia: risk factors and epidemiology. Acta Ophthalmol Scand 2002; 80:300-4.
  • 173
    Torp-Pedersen T, Boyd HA, Poulsen G, Haargaard B, Wohlfahrt J, Holmes JM, et al. In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus. Am J Epidemiol 2010; 171:868-75.
  • 174
    Tuohy PG, Counsell AM, Geddis DC. The Plunket National Child Health Study: birth defects and sociodemographic factors. N Z Med J 1993; 106:489-92.
  • 175
    Underwood P, Hester LL, Laffitte Jr. T, Gregg KV. The relationship of smoking to the outcome of pregnancy. Am J Obstet Gynecol 1965; 91:270-6.
  • 176
    van den Boogaard MJ, de Costa D, Krapels IP, Liu F, van Duijn C, Sinke RJ, et al. The MSX1 allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts. Hum Genet 2008; 124:525-34.
  • 177
    van den Eeden SK, Karagas MR, Daling JR, Vaughan TL. A case-control study of maternal smoking and congenital malformations. Paediatr Perinat Epidemiol 1990; 4:147-55.
  • 178
    van Rooij IA, Wegerif MJ, Roelofs HM, Peters WH, Kuijpers-Jagtman AM, Zielhuis GA, et al. Smoking, genetic polymorphisms in biotransformation enzymes, and nonsyndromic oral clefting: a gene-environment interaction. Epidemiology 2001; 12:502-7.
  • 179
    van Rooij IA, Groenen PM, van Drongelen M, Te Morsche RH, Peters WH, Steegers-Theunissen RP. Orofacial clefts and spina bifida: N-acetyltransferase phenotype, maternal smoking, and medication use. Teratology 2002; 66:260-6.
  • 180
    Verkerk PH, Buitendijk SE, Verloove-Vanhorick SP. Differential misclassification of alcohol and cigarette consumption by pregnancy outcome. Int J Epidemiol 1994; 23:1218-25.
  • 181
    Virtanen HE, Tapanainen AE, Kaleva MM, Suomi AM, Main KM, Skakkebaek NE, et al. Mild gestational diabetes as a risk factor for congenital cryptorchidism. J Clin Endocrinol Metab 2006; 91:4862-5.
  • 182
    Wang W, Guan P, Xu W, Zhou B. Risk factors for oral clefts: a population-based case-control study in Shenyang, China. Paediatr Perinat Epidemiol 2009; 23:310-20.
  • 183
    Wasserman CR, Shaw GM, O'Malley CD, Tolarova MM, Lammer EJ. Parental cigarette smoking and risk for congenital anomalies of the heart, neural tube, or limb. Teratology 1996; 53:261-7.
  • 184
    Watkins ML, Scanlon KS, Mulinare J, Khoury MJ. Is maternal obesity a risk factor for anencephaly and spina bifida? Epidemiology 1996; 7:507-12.
  • 185
    Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA. Maternal obesity and risk for birth defects. Pediatrics 2003; 111:1152-8.
  • 186
    Werler MM, Sheehan JE, Mitchell AA. Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia. Epidemiology 2003; 14:349-54.
  • 187
    Werler MM, Starr JR, Cloonan YK, Speltz ML. Hemifacial microsomia: from gestation to childhood. J Craniofac Surg 2009; 20 Suppl 1:664-9.
  • 188
    Werler MM, Bosco JLF, Shapira SK. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects. Birth Defects Res A Clin Mol Teratol 2009; 85:52-7.
  • 189
    Werler MM, Mitchell AA, Moore CA, Honein MA. Is there epidemiologic evidence to support vascular disruption as a pathogenesis of gastroschisis? Am J Med Genet A 2009; 149A:1399-406.
  • 190
    Wong-Gibbons DL, Romitti PA, Sun L, Moore CA, Reefhuis J, Bell EM, et al. Maternal periconceptional exposure to cigarette smoking and alcohol and esophageal atresia tracheo-esophageal fistula. Birth Defects Res A Clin Mol Teratol 2008; 82:776-84.
  • 191
    Woods SE, Raju U. Maternal smoking and the risk of congenital birth defects: a cohort study. J Am Board Fam Pract 2001; 14:330-4.
  • 192
    Wyszynski DF, Wu T. Use of US birth certificate data to estimate the risk of maternal cigarette smoking for oral clefting. Cleft Palate Craniofac J 2002; 39:188-92.
  • 193
    Yerushalmy J. The relationship of parents' cigarette smoking to outcome of pregnancy - implications as to the problem of inferring causation from the observed associations. Am J Epidemiol 1971; 93:443-56.
  • 194
    Yerushalmy J. Congenital heart disease and maternal smoking habits. Nature 1973; 242:262-3.
  • 195
    Yuan P, Okazaki I, Kuroki Y. Anal atresia: effect of smoking and drinking habits during pregnancy. Jpn J Hum Genet 1995; 40:327-32.
  • 196
    Zeiger JS, Beaty TH, Hetmanski JB, Wang H, Scott AF, Kasch L, et al. Genetic and environmental risk factors for sagittal craniosynostosis. J Craniofac Surg 2002; 13:602-6.
  • 197
    Leopércio W, Gigliotti A. Tabagismo e suas peculiaridades durante a gestação: uma revisão crítica. J Bras Pneumol 2004; 30:176-85.
  • 198
    Quinton AE, Cook CM, Peek MJ. The relationship between cigarette smoking, endothelial function and intrauterine growth restriction in human pregnancy. BJQG 2008; 115:780-4.
  • 199
    Szklo AS, de Almeida LM, Figueiredo VC, Autran M, Malta D, Caixeta R, et al. Snapshot of the striking decrease in cigarette smoking prevalence in Brazil between 1989 and 2008. Prev Med 2012; 54:162-7.
  • 200
    Salihu HM, Wilson RE. Epidemiology of parental smoking and perinatal outcomes. Early Hum Dev 2007; 83:713-20.
  • 201
    Zhang L, González-Chica DA, Cesar JA, Mendoza-Sassi RA, Beskow B, Larentis N, et al. Tabagismo materno durante a gestação e medidas antropométricas do recém-nascido: um estudo de base populacional no extremo sul do Brasil. Cad Saúde Pública 2011; 27:1768-76.
  • 202
    Tong VT, Dietz PM, Morrow B, D'Angelo DV, Farr SL, Rockhill KM, et al. Trends in smoking before, during, and after pregnancy: Pregnancy Risk Assessment Monitoring System, United States, 40 sites, 2000-2010. MMWR Surveill Summ 2013; 62:1-19.
  • 203
    Ontario Tobacco Research Unit. Indicators of smoke-free Ontario progress. Toronto: Ontario Tobacco Research Unit; 2010.
  • 204
    Bloch M, Althabe F, Onyamboko M, Kaseba-Sata C, Castilla EE, Freire S, et al. Tobacco use and secondhand smoke exposure during pregnancy: an investigative survey of women in 9 developing nations. Am J Public Health 2008; 98:1833-40.
  • 205
    Reis LG, da Silva CF, Trindade A, Abrahão M, da Silva VA. Quem são as mulheres tabagistas que param de fumar na gestação? Rev Bras Saúde Matern Infant 2008; 8:217-21.
  • 206
    Sanderson S, Iain D, Tatt ID, Higgins JPT. Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 2007; 36:666-76.

Publication Dates

  • Publication in this collection
    Dec 2014

History

  • Received
    15 June 2013
  • Reviewed
    30 June 2014
  • Accepted
    18 Aug 2014
Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz Rua Leopoldo Bulhões, 1480 , 21041-210 Rio de Janeiro RJ Brazil, Tel.:+55 21 2598-2511, Fax: +55 21 2598-2737 / +55 21 2598-2514 - Rio de Janeiro - RJ - Brazil
E-mail: cadernos@ensp.fiocruz.br