Hum. Reprod. Advance Access originally published online on March 19, 2007
Human Reproduction 2007 22(6):1730-1735; doi:10.1093/humrep/dem043
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Teenage pregnancy and congenital anomalies: which system is vulnerable?
1 OMNI Research Group, Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6 2 Clinical Epidemiology Program, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6 3 Department of Epidemiology and Community Medicine, University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada K1H 8L6 4 Pediatric Adolescent Gynecology, Children's Hospital of East Ontario, University of Ottawa, Ontario, Canada K1H 8L1
5 Correspondence address. OMNI Research Group, Department of Obstetrics and Gynecology, University of Ottawa, 501 Smyth Rd, Box 241, Ottawa, Canada K1H 8L6. Tel: +613-737-8899 ext 73912; Fax: +613-739-6266; E-mail: swwen{at}ohri.ca
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Abstract |
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BACKGROUND: Teenage pregnancy may be associated with some forms of congenital anomalies. The objective of this study was to identify the types of congenital anomalies associated with teenage pregnancy.
METHODS: We carried out a retrospective cohort study of 5 542 861 nulliparous pregnant women younger than 35 years of age with a live singleton birth between 1995 and 2000 in the USA.
RESULTS: Compared with adult pregnancy (20–34 years old), and after adjustment for confounding variables, teenage pregnancy (13–19 years old) was associated with increased risk of central nervous system anomalies [odds ratio (OR) 1.08; 95% confidence interval (CI): 1.01, 1.16], gastrointestinal anomalies (OR: 1.39; 95% CI: 1.31, 1.49) and musculoskeletal/integumental anomalies (OR: 1.06; 95% CI: 1.03, 1.10). The teenage pregnancy associated increase in risk for central nervous system anomalies was mainly attributable to anomalies other than anencephalus, spina bifida/meningocele and hydrocephalus and microcephalus; for gastrointestinal anomalies the risk was mainly attributable to omphalocele/gastroschisis; and for musculoskeletal/integumental anomalies the risk was mainly attributable to cleft lip/palate and polydactyly/syndactyly/adactyly. No increased risk was found for circulatory/respiratory anomalies, urogenital anomalies, or Down's syndrome.
CONCLUSIONS: Teenage pregnancy increases the risks of congenital anomalies in central nervous, gastrointestinal and musculoskeletal/integumental systems.
Key words: teenage/pregnancy/maternal age/congenital anomalies
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Introduction |
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Congenital anomalies are considered as leading cause of fetal and neonatal death and of childhood morbidity (Pharoah, 2005
). Based on 3% of the estimated 135 million births that occur yearly, more than 10 000 children are estimated to be born daily with congenital anomalies worldwide (Botto et al., 2004). Congenital anomalies can be attributable to intrinsic errors in a structural primordium (malformation), or some external force damaging an intrinsically well-formed structure (deformation) (Spranger et al., 1982). Chromosomal and other genetic abnormalities, environmental teratogens and certain nutritional deficiencies account for some congenital anomalies; however, the majority of congenital anomalies are of unknown etiology (Pharoah, 2005).
The majority of previous studies on the association between maternal age and congenital anomalies have focused on the strong association between advanced maternal age and chromosomal defects (Snijders et al., 1995; Reefhuis and Honein, 2004). Croen and Shaw (1995) found that the overall prevalence of all congenital anomalies across the age distribution was shown as a J shape, with women aged 20–29 years having the lowest prevalence, teenage women having an intermediate prevalence and women more than 40 years old having the highest prevalence. The prevalence of non-chromosomal anomalies tended to be a U-shaped curve, because the prevalence dropped substantially for women more than 40 years of age and only marginally for other age groups, after excluding chromosomal anomalies (Croen and Shaw, 1995). A few studies have explored the association between younger maternal age and congenital anomalies (Hay and Barbano, 1972; Haddow et al., 1993; Croen and Shaw, 1995; Hollier et al., 2000; Reefhuis and Honein, 2004), and various congenital anomalies have been identified to be associated with younger maternal age. However most previous studies on the association of maternal age with congenital anomalies did not control for potential confounders.
Based on the large population dataset in the USA, the objective of this study was to identify which types of congenital anomalies were increased in teenage pregnancy after controlling for potential confounding variables.
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Materials and Methods |
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Study population
The data were derived from the 1995–2000 nationally linked birth/infant death dataset of the USA, compiled by the National Center for Health Statistics and Centers for Disease Control and Prevention, and included information on live births and infant deaths collected from the 50 states and the District of Columbia. The dataset were pre-coded according to uniform specifications, and went through vigorous statistical quality checks by the National Center for Health Statistics. The dataset included sociodemographic information of the mothers, maternal tobacco smoking and alcohol drinking during pregnancy, status of prenatal care, complications associated with pregnancy, labour and delivery complications, congenital anomalies, birthweight, gestational age at delivery and neonatal/infant morbidity and mortality (Centers for Disease Control and Prevention/National Center for Health Statistics, 2000
).
Subjects in the present study were restricted to nulliparous women aged 13–34 years who had singleton live births between 1995 and 2000 in the USA. Because the information on congenital anomalies was not collected in New Mexico (1995–2000), subjects from this state were excluded from the study. Information on tobacco use during pregnancy was not reported from California (1995–2000), Indiana (1995–1998), South Dakota (1995–1999) and New York State (except New York City, 1995–1998). California (1995–2000) and South Dakota (1995–1999) did not include an item on alcohol use in their birth certificate. Subjects with no available information on maternal tobacco use or alcohol use from the above-mentioned states were excluded from this study, because they might be potential confounders in the observed association between teenage pregnancy and congenital anomalies (Haddow et al., 1993; Honein et al., 2000; Lorente et al., 2000). Those subjects with missing information on congenital anomalies, educational level, initiation time of prenatal care, tobacco use and alcohol use were further excluded from this study.
Definition of exposure and outcome
Maternal age was defined as the age of mother in completed years at time of delivery and was categorized into the following four groups: 13–15, 16–17, 18–19 and 20–34 years. The oldest age group was used as the reference category in the analysis, since they were considered as the normal pregnant age and had the normal risk of congenital anomalies (Centers for Disease Control and Prevention/National Center for Health Statistics, 2000).
Twenty-two categories of congenital anomalies were pre-coded by the National Center for Health Statistics according to The International Classification of Disease 9 (ICD-9) (Centers for Disease Control and Prevention/National Center for Health Statistics, 2000). The congenital anomalies in the dataset included anencephaly, spina bifida/meningocele, hydrocephaly, microcephaly, other central nervous system anomalies, heart malformations, other circulatory/respiratory anomalies, rectal atresia/stenosis, tracheo-esophageal fistula/esophageal atresia, omphalocele/gastroschisis, other gastrointestinal anomalies, malformed genitalia, renal agenesis, other urogenital anomalies, cleft lips/palate, polydactyly/syndactyly/adactyly, club foot, diaphragmatic hernia, other musculoskeletal/integumental anomalies, Down's syndrome, other chromosomal anomalies and other congenital anomalies (Centers for Disease Control and Prevention/National Center for Health Statistics, 2000). We further grouped the congenital anomalies into six categories as follows: central nervous system anomalies, circulatory/respiratory anomalies, gastrointestinal anomalies, urogenital anomalies, musculoskeletal/integumental anomalies and Down's syndrome.
Statistical analysis
We first described the distribution of maternal demographic characteristics, tobacco and alcohol use during pregnancy and initiation time of prenatal care and infant sex among different maternal age groups. In this study, the mother's educational level was defined as appropriate or inappropriate for her age, so that a consistent classification could be used for both younger and older mothers. Mothers older than 19 were considered to have an age-appropriate educational level if they had completed high school, whereas younger mothers had to have completed the minimal number of grades for their age (Fraser et al., 1995). The rates for each specific congenital anomaly were calculated within the different maternal age groups. The adjusted odds ratios (ORs) along with 95% confidence intervals (CIs) for congenital anomalies associated with teenage pregnancy were estimated by unconditional multiple logistic regression models, with the 20–34 years age group as the reference. Potential confounding variables included in the multiple regression models were state of birth, year of birth, maternal race, educational level, martial status, tobacco and alcohol use during pregnancy, initiation time of prenatal care and infant sex. All data were analysed using Statistical Analysis System, Version 9.1 (SAS Institute Inc., Cary, NC, USA).
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Results |
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There were 23 654 785 live births in the linked 1995–2000 birth and infant death dataset, among them, 7 253 898 were singletons born to nulliparous mothers aged 13–34 years old. Subjects from New Mexico (51 166) were excluded, because congenital anomalies were not included in their birth registration dataset. Subjects from California (1 002 627) in 1995–2000, South Dakota (6111) in 1995–1999, Indiana (106 030) and New York (except for New York City) (145 457) in 1995–1998 were excluded, because they lacked information on tobacco or alcohol use in their dataset. Subjects with missing information on congenital anomalies (120 122), maternal education level (79 181), initiating time of prenatal care (132 486), maternal tobacco use (63 688) or alcohol use (79 692) during pregnancy were further excluded, leaving 5 542 861 subjects for final analysis.
The maternal and infant characteristics in different maternal age groups are shown in Table 1. Compared with women aged 20–34 years, teenage mothers were more likely to be black and unmarried, to have smoked cigarettes during pregnancy and to initiate prenatal care later.
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The rates for most congenital anomalies were higher in teenage pregnancies than in adult pregnancies. The differences in rates varied among different categories of congenital anomalies (Table 2). After adjustment for confounding factors, teenage pregnancy (13–19 years old) was significantly associated with increased risk of central nervous system anomalies, gastrointestinal anomalies and musculoskeletal/integumental anomalies compared with women aged 20–34 years old (Table 3). The increased risk for central nervous system anomalies associated with teenage pregnancy was mainly attributable to anomalies other than spina bifida/meningocele, hydrocephalus; for gastrointestinal anomalies the risk was mainly attributable to omphalocele/gastroschisis and for musculoskeletal/integumental anomalies the risk was mainly attributable to cleft lip/palate and polydactyly/syndactyly/adactyly. No association was found between teenage pregnancy and circulatory/respiratory anomalies, urogenital anomalies and Down's syndrome. There was no significant exposure–response relationship between younger maternal age and increased risk of congenital anomalies.
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Discussion |
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Our large population based study found that teenage pregnancy was significantly associated with increased risk of central nervous system anomalies, gastrointestinal anomalies and musculoskeletal/integumental anomalies. The increased risk of central nervous system anomalies was mainly attributed to anomalies other than anencephalus, spina bifida/meningocele, hydrocephalus and microcephalus for gastrointestinal anomalies the risk was mainly attributed to omphalocele/gastroschisis; and for musculoskeletal/integumental anomalies the risk was mainly attributed to cleft lip/palate and polydactyly/syndactyly/adactyly. Teenage pregnancy was not associated with increased risk of circulatory/respiratory anomalies, urogenital anomalies and Down's syndrome. No significant exposure–response relationship was found in this study between younger maternal age and increased risk of congenital anomalies.
Four previous studies based on large population datasets have investigated the association between maternal age and different categories of congenital anomalies. Hay and Barbano (1972) evaluated the effects of maternal age and birth order on 16 categories of congenital anomalies based on birth certificates of more than 8 million white singleton births from 29 states and two large cities during 1961 and 1966 in the USA. The increased risks of spina bifida, positional foot defects and a combined group of omphalocele and gastroschisis were found to be associated with young maternal age. Croen and Shaw (1995) assessed the effects of maternal age on congenital malformations in a California population of over 1 million births. Compared with 25–29 years old women, young maternal age (under 20 years old) was found to be associated with 21 categories of birth defects, which reflected nearly every organ system. Defects of the central nervous system and upper limbs and deformations were frequently represented while major heart defects were nearly absent. In a study based on data from a Health and Hospital System in Texas, Hollier et al. (2000) found that younger maternal age was associated with increased crude rates of gastroschisis and polydactyly, but the association disappeared after adjusting for parity. In a recent study, Reefhuis and Honein (2004) evaluated the association between young maternal age and non-chromosomal birth defects based on the data from the Metropolitan Atlanta Congenital Defects Program (MACDP) linked with birth certificate data. Young maternal age (14–19 years old) was found to be associated with increased risk of anencephaly, hydrocephaly without neural tube defect, all ear defects, cleft lip, female genital defects, hydronephrosis, polydactyly, omphalocele and gastroschisis, when compared with 25–29 years old group.
In the above-mentioned studies, different populations, categories of congenital anomalies, sources of data, categorizations of age group, and referent groups have been applied, affecting the comparability of the research findings. The association identified in this study between younger maternal age and omphalocele/gastroschisis (Hay and Barbano, 1972; Haddow et al., 1993; Hollier et al., 2000; Reefhuis and Honein, 2004), cleft lip/palate (Croen and Shaw, 1995; Reefhuis and Honein, 2004) and polydactyly/syndactyly/adactyly (Hollier et al., 2000; Reefhuis and Honein, 2004) was consistent with some previous studies. Previous studies have found that there was no significant association between teenage pregnancy and heart malformation (Croen and Shaw, 1995; Hollier et al., 2000), consistent with the present study. In the study by Reefhuis and Honein (2004), parity, race, sex of the child and year of birth were adjusted for when they assessed the association, whereas other studies did not control for the effects of potential confounding variables (Haddow et al., 1993; Hay and Barbano, 1972; Croen and Shaw, 1995; Hollier et al., 2000).
Down's syndrome (Trisomy 21) is the most common chromosome abnormality among live births (CDC, 2006). Previous studies have indicated that the incidence increased with advancing maternal age and rose exponentially after age 35 (Hsu, 1998). So far, there has been no evidence showing the association between younger maternal age and the risk of Down's syndrome (Hsu, 1998), which was consistent with our present study. The negative finding on the association between teenage pregnancy and Down's syndrome in this study lends validity to our data.
The association between teenage pregnancy and gastroschisis has been well-established by previous studies (Goldbaum et al., 1990; Werler et al., 1992; Haddow et al., 1993; Torfs et al., 1994); such an association was further confirmed by the present study, although omphalocele and gastroschisis were not separately coded in our dataset. Since gastroschisis makes up a larger proportion of omphalocele/gastroschisis, the observed association between teenage pregnancy and this category could be largely attributed to gastroschisis. A prospective population based study indicated that pregnant women younger than 20 years of age were more likely to be affected with gastroschisis than women aged 25 years or older (OR: 7.3; 95% CI: 2.4, 22) (Haddow et al., 1993). A population based case-control study found that a short interval between menarche and first pregnancy was associated with increased risk of gastroschisis (Torfs et al., 1994). In a case-control surveillance program of births defects (76 gastroschisis cases versus 2581 malformed controls), Werler et al (1992) found a strong inverse association between maternal age and gastroschisis. Compared with women 30 years or older, the relative risks of gastroschisis for 25–29, 20–24 and younger than 20-year-old women were 1.7 (95% CI: 0.7, 4.1), 5.4 (95% CI: 2.6, 11) and 16 (95% CI: 8.1, 30). In another matched case-control study (62 gastroschisis cases and 617 unaffected infants matched for birth year), mothers less than 20 years old was found to be associated with increased risk of gastroschisis with reference to mothers 25 years and older (OR: 4.1; 95% CI: 1.4, 12.0) (Goldbaum et al., 1990). The magnitude of the observed association was lower in the present study than in previously published studies, which might be attributable to the different study population, the different design of study, the different reference group used and incompleteness of congenital anomalies reporting in the birth registration dataset.
Compared with previous studies, the most important strength of this study was the abundant maternal information in this dataset including maternal race, marital status, tobacco smoking and alcohol drinking during pregnancy, initiation time of prenatal care and infant sex, which allowed us to control for more potential confounders than did previous studies. Another important strength of our study was the large sample size, which made it possible to assess the association between teenage pregnancy and specific types of congenital anomalies and congenital anomalies in different systems. Chance and confounding factors were unlikely to explain the results of our study, because of the large sample size and adjustment for potential confounders using multivariate regression models.
Limitations in our study should not be overlooked. Some subjects were excluded because of no available information on congenital anomalies, tobacco use and alcohol use. However, these exclusions were not likely to introduce major bias into the current study, because most of them were excluded by cluster (state of birth). As an observational study, this study may be affected by residual confounding and coding errors. Birth registry data might not have complete ascertainment of congenital anomalies. There was no evidence showing the association between the accuracy of congenital anomalies reporting and maternal age. Therefore, the underreporting of congenital anomalies in birth registration was likely to occur randomly in women with different ages, and not likely to bias the observed association between teenage pregnancy and births defects. The data on smoking and alcohol consumption during pregnancy was collected retrospectively after delivery, which might lead to underreporting and recall bias on these variables. Some other potential risk factors associated with both maternal age and congenital anomalies, such as pre-pregnancy body mass index, folic acid and multivitamin supplementation before and during pregnancy and assisted reproductive technology were not collected in the present dataset, so we could not control for the effect of these confounding variables. Another limitation of our study is that the study population from birth registration data only included live-born infants. Some stillborn fetures and late abortion (selective termination) may be attributed to congenital anomalies (Hollier et al., 2000), which may affect our research findings.
The mechanisms by which teenage pregnancy may contribute to the increased risk of specific types of congenital anomalies and congenital anomalies in specific system were unclear, and our study was not designed to explore the mechanism. There may be some biological reasons why teenage mothers are at increased risk of congenital anomalies (Reefhuis and Honein, 2004), but we speculate that there are also several other possible explanations. First, the early initiation of prenatal care could lead to an increased number of terminations due to the early identification of congenital anomalies (Croen and Shaw, 1995; Reefhuis and Honein, 2004). In the present study, only 70% of teenage mothers initiated their prenatal care in the first trimester, compared to nearly 90% for adult mothers. Birth defect surveillance systems might identify more cases among younger mothers, because these cases have less opportunity to terminate an affected fetus (Hollier et al., 2000) and are more likely to be carried to term (Reefhuis and Honein, 2004). Second, factors suspected of playing a role in the etiology of some congenital anomalies such as poor diet, illicit drug use and smoking are more prevalent in teenage pregnancies than in adult pregnancies (Day et al., 1993; Croen and Shaw, 1995; Abma et al., 1997; Reefhuis and Honein, 2004). In this study, we have no available information on diet and drug use. However, we have found that the smoking rate was much higher in teenage mothers (15.97%) than in adult mothers (8.22%), which could support our hypothesis. Third, periconceptional folic acid and multivitamin supplementation have been associated with a decreased risk of neural tube defects (Czeizel and Dudas, 1992), oral clefts (Itikala et al., 2001) and heart defects (Botto et al., 2000). Previous studies have reported that younger women have lower awareness of folic acid supplementation (CDC, 1999), and have a lower use rate of multivitamins (CDC, 2001), folic acid and micronutrients (Mathews et al., 2000).
It is generally accepted that advanced maternal age (above 35 years old) is associated with increased risk of adverse birth outcome and congenital anomalies (Croen and Shaw, 1995). The information on the association of teenage pregnancy with increased congenital anomalies is not widely known (Reefhuis and Honein, 2004). This very large database study demonstrated that an increased risk of central nervous system anomalies, gastrointestinal anomalies and musculoskeletal/integumental anomalies was associated with teenage pregnancy. Although the etiology of some congenital anomalies needs further study, some lifestyle related factors associated with increased risk of congenital anomalies in teenage pregnancy offer us some opportunity for prevention. If teenage mothers get adequate prenatal care, have a healthy diet, avoid exposure to smoke, alcohol and drugs and take timely multivitamin and folic acid supplements, some of these congenital anomalies may be prevented (Reefhuis and Honein, 2004). The findings of this study have a significant public health impact.
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X-K.C. is a recipient of CIHR/STIRRHS Post-PhD fellowship. S.W.W. and M.C.W. are recipients of New Investigator's Award from CIHR.
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References |
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Abma JC, Chandra A, Mosher WD, et al. (1997) Fertility, family planning, and women's health: new data from the 1995 National Survey of Family Growth. Vital Health Stat 23:1–114.
Botto LD, Mulinare J, Erickson JD. (2000) Occurrence of congenital heart defects in relation to maternal multivitamin use. Am J Epidemiol 151:878–84.
Botto LD, Olney RS, Erickson JD. (2004) Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet 125:12–21.[Medline]
Centers for Disease Control and Prevention (CDC). (1999) Knowledge and use of folic acid by women of childbearing age–United States, 1995 and 1998. MMWR Morb Mortal Wkly Rep 48:325–7.[Medline]
Centers for Disease Control and Prevention (CDC). (2001) Knowledge and use of folic acid among women of reproductive age–Michigan, 1998. MMWR Morb Mortal Wkly Rep 50:185–9.[Medline]
Centers for Disease Control and Prevention (CDC). (2006) Improved national prevalence estimates for 18 selected major birth defects–United States, 1999–2001. MMWR Morb Mortal Wkly Rep 54:1301–5.[Medline]
Centers for Disease Control and Prevention/National Center for Health Statistics. (2000) Linked birth/infant death data set:1998 birth cohort data. CD-ROM.
Croen LA and Shaw GM. (1995) Young maternal age and congenital malformations: a population-based study. Am J Public Health 85:710–3.
Czeizel AE and Dudas I. (1992) Prevention of the first occurrence of neural tube defects by periconceptional vitamin supplementation. N Engl J Med 327:1832–5.[Abstract]
Day NL, Cottreau CM, Richardson GA. (1993) The Epidemiology of alcohol, marijuana, and cocaine use among women of childbearing age and pregnant women. Clin Obstet Gynecol 36:232–45.[CrossRef][ISI][Medline]
Fraser AM, Brockert JE, Ward RH. (1995) Association of young maternal age with adverse reproductive outcomes. N Engl J Med 332:1113–7.
Goldbaum G, Daling J, Milham S. (1990) Risk factors for gastroschisis. Teratology 42:397–403.[CrossRef][ISI][Medline]
Haddow JE, Palomaki GE, Holman MS. (1993) Young maternal age and smoking during pregnancy as risk factors for gastroschisis. Teratology 47:225–8.[CrossRef][ISI][Medline]
Hay S and Barbano H. (1972) Independent effects of maternal age and birth order on the incidence of selected congenital malformations. Teratology 6:280.
Hollier LM, Leveno KJ, Kelly MA, et al. (2000) Maternal age and malformations in singleton births. Obstet Gynecol 96:701–6.
Honein MA, Paulozzi LJ, Moore CA. (2000) Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction. Am J Epidemiol 152:658–65.
Hsu LY. (1998) Prenatal diagnosis of chromosomal abnormalities through amniocentesis. In Milunsky W (Ed.). Genetic Disorders and the Fetus: Diagnosis, Prevention, and Treatment. Baltimore and LondonThe Johns Hopkins University Press pp. 181.
Itikala PR, Watkins ML, Mulinare J, et al. (2001) Maternal multivitamin use and orofacial clefts in offspring. Teratology 63:79–86.[CrossRef][ISI][Medline]
Lorente C, Cordier S, Goujard J, et al. (2000) Tobacco and alcohol use during pregnancy and risk of oral cleft. Occupational Exposure and Congenital Malformation Working Group. Am J Public Health 90:415–19.
Mathews F, Yudkin P, Smith RF, et al. (2000) Nutrient intakes during pregnancy: the influence of smoking status and age. J Epidemiol Community Health 54:17–23.
Pharoah PO. (2005) Causal hypothesis for some congenital anomalies. Twin Res Hum Genet 8:543–50.[CrossRef][ISI][Medline]
Reefhuis J and Honein MA. (2004) Maternal age and non-chromosomal birth defects, Atlanta-1968–2000: teenager or thirty-something, who is at risk? Birth Defects Res A Clin Mol Teratol 70:572–9.[CrossRef][ISI][Medline]
Snijders RJ, Sebire NJ, Nicolaides KH. (1995) Maternal age and gestational age-specific risk for chromosomal defects. Fetal Diagn Ther 10:356–67.[ISI][Medline]
Spranger J, Benirshke K, Hall JG, et al. (1982) Errors of morphogenesis: concepts and terms. J Pediatr 100:160–5.[CrossRef][ISI][Medline]
Torfs CP, Velie EM, Oechsli FW, et al. (1994) A population-based study of gastrochisis: demographic, and pregnancy, lifestyle risk factors. Teratology 1:53.
Werler MM, Mitchell AA, Shapiro S. (1992) Demographic, reproductive, medical, and environmental factors in relation to gastroschisis. Teratology 45:353–60.[CrossRef][ISI][Medline]
Submitted on December 6, 2006; resubmitted on January 22, 2007; accepted on January 31, 2007.
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