Skip Navigation



American Journal of Epidemiology Advance Access published online on October 3, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn248
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
168/11/1259    most recent
kwn248v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Slickers, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Slickers, J. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Original Contribution

Maternal Body Mass Index and Lifestyle Exposures and the Risk of Bilateral Renal Agenesis or Hypoplasia

The National Birth Defects Prevention Study

Jennifer E. Slickers, Andrew F. Olshan, Anna Maria Siega-Riz, Margaret A. Honein, Arthur S. Aylsworth and for the National Birth Defects Prevention Study

Correspondence to Dr. Andrew F. Olshan, Department of Epidemiology, Campus Box 7435, School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7435 (e-mail: andy_olshan{at}unc.edu).

Received for publication March 3, 2008. Accepted for publication July 16, 2008.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Increased maternal body mass index, maternal smoking, and alcohol exposure during pregnancy have been inconsistently reported as potential risk factors for renal birth defects. The low incidence of the most severe renal anomaly, bilateral renal agenesis or hypoplasia (RA/H), has limited the ability to study this fatal defect. Using data from the National Birth Defects Prevention Study, a multicenter case-control study, the authors explored potential relations between RA/H and maternal body mass index, smoking, alcohol, and caffeine exposures. Data available for 75 infants with RA/H born between 1997 and 2003 and for randomly selected control infants without known birth defects (n = 868) were assessed by a model adjusted for folic acid use, all four exposures of interest, and study center. Bilateral RA/H was associated with a body mass index of greater than 30 kg/m2 prior to pregnancy (adjusted odds ratio (aOR) = 1.92, 95% confidence interval (CI): 1.00, 3.67), smoking during the periconceptional period (aOR = 2.09, 95% CI: 1.08, 4.03), and binge drinking during the second month of pregnancy (aOR = 3.64, 95% CI: 1.19, 11.1). These results support the need for further exploration into the potential mechanisms by which such exposures could interfere with early fetal kidney formation resulting in RA/H.

alcohol drinking; body mass index; caffeine; case-control studies; congenital abnormalities; kidney; pregnancy; smoking

Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; OR, odds ratio; RA/H, bilateral renal agenesis or hypoplasia


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Bilateral renal agenesis, or absent kidney development, is a fatal congenital anomaly affecting approximately 1–3 per 10,000 births (1, 2). The absence of kidneys in utero results in severe oligohydramnios and poor lung development, generally incompatible with survival (3, 4). Renal hypoplasia, or underdeveloped kidneys, occurring bilaterally or in combination with renal agenesis can also be fatal but even in surviving infants leads to increased risk of chronic kidney disease and hypertension (5).

The causes of bilateral renal agenesis or hypoplasia (RA/H) remain unknown. Several potential risk factors for renal anomalies in general are represented in the literature. Parikh et al. (6) reported evidence that renal agenesis occurs more frequently among women with lower educational levels and evidence suggesting that younger age and African-American race might also pose a higher risk, in contrast to earlier publications not supporting age or race associations (2, 7). Inconsistent findings have also been reported for a high prepregnancy body mass index, maternal smoking, alcohol ingestion, and caffeine consumption during pregnancy (6, 8–16). Honein et al. (9) reported a possible interaction between obesity and subfertility and the risk of renal anomalies. Hypothyroidism was not found to be related (17), and several studies have reported possible associations between vasoactive substances and congenital renal anomalies (18–21). Diabetic status has yielded conflicting results (6, 8, 22, 23). Interpreting these results is complicated because many of these studies group together multiple renal and urologic birth defects that likely develop from different pathophysiologic mechanisms (8, 12–14, 24). The goal of this study is to investigate potential associations between RA/H and a high prepregnancy body mass index, first trimester smoke or alcohol exposure, and caffeine intake during pregnancy, by using data from a national, population-based, case-control study.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Data for this analysis are from the National Birth Defects Prevention Study, a case-control study sponsored by the Centers for Disease Control and Prevention. Details of data collection for this study have been published (25–27). Cases represent infants diagnosed with RA/H (International Classification of Diseases, Ninth Revision, codes 753.000 and 753.005–8) identified through population-based surveillance systems in 10 states and include live- and stillbirths as well as elective terminations. Liveborn controls without identified major birth defects were randomly selected at each study center by using birth files or hospital records. Maternal medical and exposure histories were collected retrospectively through structured, computer-assisted telephone interviews within 24 months of delivery. The participation was 63% among cases with RA/H and 69% among controls. Cases were reviewed by a clinical geneticist at each center, and classification by a clinical geneticist from our study team (A. S A.) confirmed that the case definition was met. (The classification template is available from the corresponding author.) Cases of RA/H that occurred in combination with other anomalies were included unless a well-defined genetic syndrome was identified or strongly suspected, yielding a total of 80 cases with a maternal interview (51 classified as having an isolated defect). Among the cases, 71 had bilateral renal agenesis, 5 had bilateral renal hypoplasia, and 4 had one absent and one hypoplastic kidney. Approximately 10 controls for each case were selected randomly from the control pool for this analysis (n = 870). The 5 cases and 2 controls born to mothers with diabetes diagnosed before pregnancy were excluded, leaving 75 cases and 868 controls for the analysis.

The exposures included a high prepregnancy body mass index, periconceptional smoke and alcohol exposure, and caffeine consumption. Prepregnancy body mass index (weight (kg)/height (m)2) was calculated by using self-reported prepregnancy values. Women were classified according to National Institutes of Health (28) definitions, with a body mass index of 25–29.9 kg/m2 being classified as overweight and a body mass index of ≥30 kg/m2 being classified as obese; women with a body mass index of <25 kg/m2 formed the reference category. The primary analysis utilized this classification, and further analysis was conducted with additional groupings for underweight (body mass index, <18.5 kg/m2) and extreme obesity (body mass index, ≥40 kg/m2).

Maternal smoking and alcohol exposures were also obtained. Exposures reported to occur between the month prior to conception through the third month of pregnancy were classified as "periconceptional," the timeframe utilized for our analysis.

Women were asked about smoking and secondhand exposure in the home or work environment. Nonsmoking women who denied secondhand smoke exposure formed the unexposed reference group. Smoking was analyzed as a 3-category variable with secondhand smoke exposure as an intermediate classification. A secondary analysis was conducted by using the maximum level of reported smoking during periconception.

The same timeframe of "periconceptional" exposure was also applied to alcohol use. Alcohol questions for each month specifically documented the number of days and drinks that occurred during each month, as well as the maximum number of drinks that occurred at 1 sitting during each month. Alcohol exposure was represented by a 3-category variable, subdivided into that occurring with and without binge drinking (defined as ≥5 drinks on one occasion). Data on the number of binge episodes per month were not collected. For both smoke and alcohol exposures, these relations were individually explored for the 4 contributing periconceptional months.

Questions pertaining to caffeine intake were collected differently from those for the other exposures, documenting the typical daily intake of coffee, tea, and soda consumption the year prior to pregnancy. A continuous variable reflecting mean daily caffeine intake was generated on the basis of the estimated caffeine content (mg/serving) of these major caffeine sources (29, 30). Mothers were also asked about changes (more, same, less, or none ingested) in these sources of caffeine during the pregnancy when compared with the prior year. Because the calculated daily caffeine intake did not necessarily reflect intake during pregnancy, a variable was created to better represent caffeine intake during pregnancy and to broadly capture whether the intake was negligible or not. Caffeine intake during pregnancy was defined as negligible if one of the following criteria was met: 1) maternal report of no coffee, tea, or soda consumption during pregnancy; 2) a mean daily caffeine intake of less than 10 mg prior to pregnancy and no reported increase in coffee, tea, and soda consumption; or 3) a mean daily caffeine intake of less than 50 mg prior to pregnancy, reduced consumption in at least one caffeinated beverage category, and no accompanying increase in another caffeine source. A secondary analysis was also performed by using the continuous expression of caffeine intake among only those reporting the same level of consumption during pregnancy.

Factors initially explored as potential confounders were based on previous studies and included maternal age, maternal race/ethnicity, maternal educational level, study center, folic acid use, gestational diabetes, hypothyroidism, subfertility, late pregnancy identification, and vasoactive substance use. Maternal age was analyzed as a continuous linear variable. Maternal race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, Hispanic, or other. Educational level was classified as either ≤12 years or >12 years of completed education and was used as a proxy for socioeconomic status instead of household income, because the latter had considerably more missing data and did not account for the number of people supported in the household. Folic acid supplementation was represented by using a variable indicating the number of periconceptional months that folic acid was reportedly used (ranging from 0 to 4 months). Hypothyroidism was determined by maternal report or the presence of thyroid replacement hormone among the reported medications. Subfertility was based upon queries regarding maternal medications or procedures to facilitate pregnancy. Late pregnancy identification was defined as reported maternal recognition of pregnancy after 12 weeks’ gestation. Vasoactive substance use incorporated the maternal report of any of the following during the first trimester: aspirin, ibuprofen, pseudoephedrine sulfate, ephedrine sulfate, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, methylendioxymethamphetamine, cocaine, or amphetamine.

Statistical analysis was performed by using Intercooled Stata 9.2 (StataCorp LP, College Station, Texas). Following univariate and bivariate analysis exploring the relations between covariates, case status, and exposures of interest, a logistic regression model was constructed to estimate odds ratios and 95% confidence intervals for all the exposures of interest, adjusting for relevant covariates. The initial model incorporated all the potential confounders that were associated with either exposure or case status or previously explored in the literature as a risk factor. We then used backward selection, dropping those whose absence was associated with a less than 10% change in the odds ratios for all of the exposures of interest. Potential interactions between each of the exposures of interest and relevant covariates were explored by using product terms and likelihood ratio testing. Subanalyses were performed by using the final adjusted model. For the secondary analyses of the individual months, parallel models were used that included the same covariates but incorporated exposure data for smoking and alcohol for the individual months rather than the entire periconceptional period. The final adjusted model was also run separately for both isolated cases of RA/H and those occurring with multiple defects.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
The analysis included 75 cases and 868 controls. The distribution of maternal age and race/ethnicity did not differ materially between cases and controls (Table 1). Nearly all case infants were deceased at the time of interview. Neither pregnancy intention nor mean time of pregnancy identification differed substantively between cases and controls, although case pregnancies were nearly twice as likely as controls to be identified after the first trimester (6.9% vs. 3.5%). Folic acid supplementation was more prevalent among controls throughout periconception, and this was associated with later pregnancy identification: When pregnancy was identified after 12 weeks, the odds ratio of periconceptional folate use was 0.06 (95% confidence interval (CI): 0.029, 0.13). When pregnancy was identified after 12 weeks, maternal education and income were lower among case mothers than controls. Gestational diabetes was more prevalent among controls than cases. The prevalences of hypothyroidism and subfertility were too low to allow further exploration.


View this table:
[in this window]
[in a new window]

  		Table 1. Characteristics of Mothers of Infants With Bilateral Renal Agenesis or Hypoplasia (Cases) and Infants With No Birth Defects (Controls), National Birth Defects Prevention Study, 1997–2003

 
Both body mass index and smoke exposure differed between cases and controls (Table 2). The mean body mass index before pregnancy among case mothers was 26.6 kg/m2 versus 24.5 kg/m2 among control mothers, with a higher proportion of case mothers classified as obese (25% vs. 15%); 36% of case mothers reported smoking at some time during periconception as opposed to 21% of control mothers, with a similar relation observed for secondhand smoke exposure. This general relation persisted when refined by monthly exposure.


View this table:
[in this window]
[in a new window]

  		Table 2. Frequency of Selected Exposures Among Mothers of Infants With Bilateral Renal Agenesis or Hypoplasia (Cases) and Infants With No Birth Defects (Controls), National Birth Defects Prevention Study, 1997–2003

 
Exposures to alcohol and caffeine did not vary significantly between cases and controls, with the exception of those reporting binge drinking (Table 2). Exposure to alcohol anytime during the first trimester was 43% among cases versus 37% among controls. Nearly twice the proportion of case mothers reported binge drinking compared with controls. Although this observation was true for each contributing month, it was most pronounced in the second month with 8.2% of cases and 1.8% of controls reporting binge drinking. Notably, binge drinking was associated with pregnancy identification after 12 weeks’ gestation (odds ratio (OR) = 2.42, 95% CI: 1.03, 5.72). The mean intake of caffeine was very similar between cases and controls, and this persisted when restricted to only those participants reporting unchanged caffeine consumption during pregnancy and for nonnegligible caffeine classification.

The variables used for the initial adjusted model included maternal age, maternal race/ethnicity, maternal educational level, study center, folic acid use, gestational diabetes, hypothyroidism, late pregnancy identification, subfertility, vasoactive substance use, and all of the exposures of interest (body mass index, smoking, alcohol, and caffeine). Only folic acid and study center persisted as relevant covariates in the final adjusted model. Of the interactions explored, only one was marginally significant (P = 0.04 in the likelihood ratio test) between body mass index and caffeine. There was a suggestion that caffeine had a reduced risk for the overweight and an increased risk for the obese. This interaction was not pursued further, because of concerns that it was due to chance or biologic implausibility.

The adjusted odds ratio for prepregnancy body mass index of ≥30 kg/m2 was 1.90 (95% CI: 1.00, 3.59) (Table 3). Although imprecise, a stronger association was found with further subdivision of body mass index, where a body mass index of ≥40 kg/m2 conferred an adjusted odds ratio of 6.30 (95% CI: 2.13, 18.6), while the adjusted odds ratios for the other categories ranged from 1.26 to 1.44 (all 95% CIs crossing 1) when compared with a body mass index of 18.5–24.9 kg/m2. This relation persisted (adjusted odds ratio = 6.23, 95% CI: 1.89, 20.6) when restricted to those without gestational diabetes. There were insufficient cases to repeat the model among only those with gestational diabetes.


View this table:
[in this window]
[in a new window]

  		Table 3. Logistic Regression Results for Bilateral Renal Agenesis or Hypoplasia and Selected Exposures of Interest During the Month Prior to Pregnancy Through the First Trimester, National Birth Defects Prevention Study, 1997–2003

 
Smoking at anytime during periconception yielded an adjusted odds ratio of 2.08 (95% CI: 1.11, 3.90) and 1.47 (95% CI: 0.71, 3.02) for secondhand smoke exposure (Table 3). These numbers remained similar when confined to each of the 4 contributing months. Maximum daily smoking during periconception in packs per day, categorized as ≤1/2, 1, or >1 pack per day, yielded adjusted odds ratios of 1.86 (95% CI: 0.97, 3.55), 1.63 (95% CI: 0.61, 4.36), and 6.82 (95% CI: 1.15, 40.3), respectively.

Alcohol exposure during periconception yielded adjusted odds ratios of 1.35 (95% CI: 0.73, 2.51) and 1.94 (95% CI: 0.90, 4.18) for non-binge drinking and binge drinking, respectively. When examined by month, a strong effect was observed only during the second month of pregnancy for binge drinking (aOR = 3.64, 95% CI: 1.19, 11.1).

Caffeine intake was not associated with an elevated risk with either nonnegligible classification during pregnancy (aOR = 1.01, 95% CI: 0.58, 1.75) or using the continuous caffeine intake variable among those reporting unchanged caffeine intake during pregnancy (aOR = 0.997, 95% CI: 0.993, 1.002).

Analyses confined to the 51 isolated cases of RA/H yielded less precise yet similar point estimates for obesity (aOR = 1.87, 95% CI: 0.85, 4.08) and smoking (aOR = 2.69, 95% CI: 1.22, 5.92), with no relation evident for drinking (for non-binge drinking, aOR = 0.97; for binge drinking, aOR = 1.13). Repeating the model among only the 24 cases occurring with multiple anomalies yielded adjusted odds ratios of 3.07 for non-binge drinking (95% CI: 0.99, 9.54) and 5.25 for binge drinking (95% CI: 1.51, 18.2), 2.31 for obesity (95% CI: 0.79, 6.79), and 1.70 for smoking (95% CI: 0.54, 5.36). When restricted to second month exposures, the adjusted odds ratio for non-binge drinking was 6.69 (95% CI: 1.88, 23.7) and 19.0 for binge drinking (95% CI: 4.39, 82.1).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
The results from this study suggest that prepregnancy obesity and smoking during periconception independently increase the likelihood of bilateral fetal RA/H. They also suggest that alcohol consumption, particularly binge drinking and/or alcohol ingestion during the second month of pregnancy, may increase the risk of bilateral RA/H, potentially accompanied by other defects. We did not find any associations with caffeine intake.

Elevated body mass index has been reported as a potential risk factor for congenital renal anomalies in some, but not all, prior studies. Queisser-Luft et al. (31) found an association with renal agenesis and a body mass index of ≥30 kg/m2 (OR = 4.1, 95% CI: 1.3, 12.9), while Watkins et al. (10) reported none, with similar outcome and exposure specifications (OR = 0.8, 95% CI: 0.2, 3.9). Honein et al. (9) demonstrated that, among women experiencing difficulties achieving pregnancy, a body mass index of ≥25 kg/m2 conferred a higher likelihood of renal and urinary anomalies including renal agenesis (OR = 5.8, 95% CI: 2.0, 16.3). Martinez-Frias et al. (8) reported an effect of diabetes among obese women, where only among women with a body mass index of >29.9 kg/m2 was gestational diabetes associated with increased odds of congenital anomalies (including renal) (OR = 2.76, 95% CI: 1.49, 5.11); among nondiabetics, a body mass index of >29.9 kg/m2 was not associated with an increased risk (OR = 0.93, 95% CI: 0.71, 1.23). The prior association with subfertility could not fully be explored in this study because no cases reported subfertility. The results presented in the current study demonstrate that the association between obesity and RA/H is not dependent upon the presence of diabetes. Alternative endocrine products, such as those derived from adipose tissue directly, or the increased inflammation that accompanies obesity (32) could introduce epigenomic changes that interfere with gene expression critical for renal development. For instance, Zhu et al. (33) recently reported a direct link between increased levels of tumor necrosis factor-alpha, a known inflammatory agent released in high quantities from human adipose tissue (32), and interference with bone morphogenetic protein-4 expression in the lung, impeding epithelial branching during lung development. This protein plays a similar role in the kidney, guiding ureteric bud formation and branching (34), thus presenting one potential means by which adipose-related inflammation could interfere with renal development. Alternatively, obesity could be a marker of another process or exposure that we are not directly measuring that could account for this observed association.

With regard to smoking, Parikh et al. (6) found a weak association between renal agenesis and smoking with a higher proportion of smokers among cases than controls (18% vs. 14%; P = 0.059), and Kallen (11) found a weak association between renal anomalies and smoking early in pregnancy (OR = 1.22, 95% CI: 1.00, 1.48). This is in contrast to results presented by Morales-Suárez-Varela et al. (13) where urinary anomalies were not associated with first trimester smoking (OR = 0.7, 95% CI: 0.5, 1.0). The results presented here lend further support to smoking as a potential risk factor for RA/H. Although a dose-response relation was not demonstrated when representing magnitude of smoking by the maximum reported level of smoking during periconception, this variable was limited in that it did not account for the duration at which that level of smoking persisted. The fact that secondhand smoke yields an intermediate point estimate might at least suggest a potential dose-response relation.

One possible mechanism by which smoking could lead to RA/H, as with obesity, could be through chronic inflammation resulting from smoke exposure. Alternatively, the vasoconstrictive properties of nicotine may play a role (35), interfering with adequate oxygen delivery during renal organogenesis. This association might also arise secondarily to other components of cigarette smoke, such as aromatic amines, known for their carcinogenicity (36), also presenting potential for teratogenicity (37).

At least 2 prior studies have suggested a relation between alcohol exposure during pregnancy and renal agenesis (6, 12). Parikh et al. (6) found an odds ratio of 2.30 (95% CI: 0.97, 5.42) for any alcohol use during pregnancy and renal agenesis. Moore et al. (12) reported an association between alcohol exposure during the first trimester and RA/H, with the strongest associations for bilateral disease (OR = 3.7, 95% CI: 1.3, 10.1) and when renal agenesis was one of multiple congenital anomalies (OR = 2.6, 95% CI: 1.1, 6.3). These associations were strengthened when confined to women who reported binge drinking, defined as ≥5 drinks at one setting. Our findings are quite similar, reinforcing that binge drinking in periconception appears to be associated with RA/H, particularly among cases occurring with multiple anomalies. It should be pointed out that binge drinking was also associated with later pregnancy identification, so this association could be related to effects of delayed prenatal care or knowledge of the pregnancy. However, adjustment for these factors did not change our results.

This study also introduces the suggestion that the second month of pregnancy might represent a critical period of vulnerability during which acute exposures to teratogens could increase the risk of RA/H. This makes sense from a developmental perspective, as it is during the second month of pregnancy that the ureteric bud originates from the mesonephric duct and extends toward the metanephric mesenchyme to initiate formation of the adult kidney (38). Proposed teratogenic mechanisms of alcohol include transient vasospasm of the umbilical vessels (39) or increased oxidative stress and apoptosis (40).

The current study had several limitations that should be recognized. The small number of cases, because of the low incidence of RA/H, limited the ability to precisely explore dose-response relations and interactions. Despite this, some relatively precise effect estimates were obtained. The nature of the exposure data is also susceptible to recall bias because it is collected retrospectively, cases were often not liveborn, and the time lapse between pregnancy and interview might negatively impact reporting accuracy. Smoking and alcohol use during pregnancy are also socially undesirable behaviors, potentially leading to differential reporting, with case mothers more likely to underreport behaviors they might associate as potential contributors to the negative outcomes they experienced (41–43). This potential for differential recall bias is further enhanced by the fact that case interviews took place on average over 2 months later than control interviews, inherently increasing the level of uncertainty in the ability for case mothers to accurately recall information relative to control mothers. The caffeine exposure data are particularly susceptible to inaccurate recall, as they reflect intake recalled from the year prior to pregnancy. By using a variable that reflects intake during the pregnancy, precision was lost, potentially obscuring subtle relations. Self-reported body mass index has been shown to underestimate the true body mass index among all women (44, 45); however, the potential for differential reporting might be smaller because obesity might be less recognized than smoking or alcohol use as a potential risk factor for negative pregnancy outcomes.

Interpreting the existing literature in this area has been severely complicated by the fact that often renal and urologic anomalies that likely arise from different pathophysiologic mechanisms are grouped as a single outcome (46). This study better clarifies the potential existence of associations between bilateral RA/H and prepregnancy obesity, periconceptional smoking, and binge drinking during the second month of pregnancy because of the more narrowly defined case group of RA/H. Further investigation is needed to reproduce these results in another data set and to elucidate potential mechanisms by which these exposures might interfere with renal development. Continued research in this area could reveal preventable causes of this lethal congenital anomaly and also open lines of investigation to further understand renal development.


   ACKNOWLEDGMENTS
 
Author affiliations: UNC Kidney Center, University of North Carolina, Chapel Hill, North Carolina (Jennifer E. Slickers); Department of Epidemiology, School of Public Health, Chapel Hill, North Carolina (Jennifer E. Slickers, Andrew F. Olshan, Anna Maria Siega-Riz); Department of Nutrition, School of Public Health, Chapel Hill, North Carolina (Anna Maria Siega-Riz); National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia (Margaret A. Honein); and Departments of Pediatrics and Genetics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina (Arthur S. Aylsworth).

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Cohen HL, Kravets F, Zucconi W, et al. Congenital abnormalities of the genitourinary system. Semin Roentgenol (2004) 39(2):282–303.[CrossRef][Web of Science][Medline]
  2. Bianchi DW, Crombleholme TM, D'Alton ME. Renal agenesis. In: Fetology: Diagnosis and Management of the Fetal Patient (2000) New York, NY: McGraw-Hill. 641–647.
  3. Potter EL. Bilateral renal agenesis. J Pediatr (1946) 29:68.[CrossRef][Web of Science]
  4. Potter EL. Bilateral absence of ureters and kidneys: a report of 50 cases. Obstet Gynecol (1965) 25(1):3–12.[Web of Science][Medline]
  5. Brenner BM, Chertow GM. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis (1994) 23(2):171–175.[Web of Science][Medline]
  6. Parikh CR, McCall D, Engelman C, et al. Congenital renal agenesis: case-control analysis of birth characteristics. Am J Kidney Dis (2002) 39(4):689–694.[CrossRef][Web of Science][Medline]
  7. Leck I, Lancashire RJ. Birth prevalence of malformations in members of different ethnic groups and in the offspring of matings between them, in Birmingham, England. J Epidemiol Community Health (1995) 49(2):171–179.[Abstract/Free Full Text]
  8. Martínez-Frías ML, Frías JP, Bermejo E, et al. Pre-gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes. Diabet Med (2005) 22(6):775–781.[CrossRef][Web of Science][Medline]
  9. Honein MA, Moore CA, Watkins ML. Subfertility and prepregnancy overweight/obesity: possible interaction between these risk factors in the etiology of congenital renal anomalies. Birth Defects Res A Clin Mol Teratol (2003) 67(8):572–577.[CrossRef][Web of Science][Medline]
  10. Watkins ML, Rasmussen SA, Honein MA, et al. Maternal obesity and risk for birth defects. Pediatrics (2003) 111(5 pt 2):1152–1158.[Abstract/Free Full Text]
  11. Källen K. Maternal smoking and urinary organ malformations. Int J Epidemiol (1997) 26(3):571–574.[Abstract/Free Full Text]
  12. Moore CA, Khoury MJ, Liu Y. Does light-to-moderate alcohol consumption during pregnancy increase the risk for renal anomalies among offspring? [Electronic article]. Pediatrics (1997) 99(4):E11.
  13. Morales-Suárez-Varela MM, Bille C, Christensen K, et al. Smoking habits, nicotine use and congenital malformations. Obstet Gynecol (2006) 107(1):51–57.[Web of Science][Medline]
  14. Taylor CL, Jones KL, Jones MC, et al. Incidence of renal anomalies in children prenatally exposed to ethanol. Pediatrics (1994) 94(2 pt 1):209–212.[Abstract/Free Full Text]
  15. McDonald AD, Armstrong BG, Sloan M. Cigarette, alcohol and coffee consumption and congenital defects. Am J Public Health (1992) 82(1):91–93.[Abstract/Free Full Text]
  16. Browne ML. Maternal exposure to caffeine and risk of congenital anomalies: a systematic review. Epidemiology (2006) 17(3):324–331.[CrossRef][Web of Science][Medline]
  17. Khoury MJ, Becerra JE, d'Almada PJ. Maternal thyroid disease and risk of birth defects in offspring: a population-based case-control study. Paediatr Perinat Epidemiol (1989) 3(4):402–420.[Medline]
  18. Mitra SC, Ganesh V, Apuzzio JJ. Fetus-placenta-newborn: effect of maternal cocaine abuse on renal arterial flow and urine output of the fetus. Am J Obstet Gynecol (1994) 171(6):1556–1559.[Web of Science][Medline]
  19. Kashiwagi M, Chaoui R, Stallmach T, et al. Fetal bilateral renal agenesis, phocomelia and single unbilical artery associated with cocaine abuse in early pregnancy. Birth Defects Res A Clin Mol Teratol (2003) 67(11):951–952.[CrossRef][Web of Science][Medline]
  20. Abe K, Honein MA, Moore CA. Maternal febrile illnesses, medication use, and the risk of congenital renal anomalies. Birth Defects Res A Clin Mol Teratol (2003) 67(11):911–918.[CrossRef][Web of Science][Medline]
  21. Boubred F, Vendemmia M, Garcia-Meric P, et al. Effects of maternally administered drugs on the fetal and neonatal kidney. Drug Saf (2006) 29(5):397–419.[CrossRef][Web of Science][Medline]
  22. Becerra JE, Khoury MJ, Cordero JF, et al. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics (1990) 85(1):1–9.[Abstract/Free Full Text]
  23. Moore LL, Singer MR, Bradlee ML, et al. A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology (2000) 11(6):689–694.[CrossRef][Web of Science][Medline]
  24. Holmes LB. Prevalence, phenotypic heterogeneity and familial aspects of bilateral renal agenesis/dysgenesis. In: Genetics of Kidney Disorders—Bartsocas CS, ed. (1989) New York, NY: Alan R Liss.
  25. Yoon PW, Rasmussen SA, Moore CA, et al. The National Birth Defects Prevention Study. Public Health Rep (2001) 116(suppl 1):32–40.[Web of Science][Medline]
  26. Rasmussen SA, Olney RS, Holmes LB, et al. Guidelines for case classification for the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol (2003) 67(3):193–201.[CrossRef][Web of Science][Medline]
  27. Congenital malformations surveillance report: a report from the National Birth Defects Prevention Network. Teratology (2000) 61(1–2):1–160.[CrossRef][Web of Science][Medline]
  28. National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (1998) Bethesda, MD: National Institutes of Health. (NIH publication no. 98-4083).
  29. Bracken MB, Triche E, Grosso L, et al. Heterogeneity in assessing self-reports of caffeine exposure: implications for studies of health effects. Epidemiology (2002) 13(2):165–171.[CrossRef][Web of Science][Medline]
  30. Browne ML, Bell EM, Druschel CM, et al. Maternal caffeine consumption and risk of cardiovascular malformations. Birth Defects Res A Clin Mol Teratol (2007) 79(7):533–543.[CrossRef][Web of Science][Medline]
  31. Queisser-Luft A, Kieninger-Baum D, Menger H, et al. Does maternal obesity increase the risk of fetal anomalies? Analysis of 20,248 newborn infants of the Mainz Birth Register for detecting congenital anomalies. Ultraschall Med (1998) 19(1):40–44.[Web of Science][Medline]
  32. Alum I, Lewis K, Stephens JW, et al. Obesity, metabolic syndrome and sleep apnoea: all pro-inflammatory states. Obes Rev. (2007) 8(2):119–127.[CrossRef][Web of Science][Medline]
  33. Zhu NL, Li C, Huang HH, et al. TNF-alpha represses transcription of human bone morphogenetic protein-4 in lung epithelial cells. Gene (2007) 393(1–2):70–80.[CrossRef][Web of Science][Medline]
  34. Miyazaki Y, Oshima K, Fogo A, et al. Evidence that bone morphogenetic protein-4 has multiple biological functions during kidney and urinary tract development. Kidney Int (2003) 63(3):835–844.[CrossRef][Web of Science][Medline]
  35. Xiao DL, Huang X, Yang S, et al. Direct effects of nicotine on contractility of the uterine artery in pregnancy. J Pharmacol Exp Ther (2007) 322(1):180–185.[Abstract/Free Full Text]
  36. Telaska G. Aromatic amines and human urinary bladder cancer: exposure sources and epidemiology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. (2003) 21(1):29–43.[CrossRef][Web of Science][Medline]
  37. Davis KR, Scholtz TW, Dumont JN. Toxic and teratogenic effects of selected aromatic amines on embryos of the amphibian Xenopus laevis. Arch Environ Contam Toxicol (1981) 10(3):371–391.[CrossRef][Web of Science][Medline]
  38. Vize PD, Woolf AS, Bard JBL. The Kidney: From Normal Development to Congenital Disease (2003) San Diego, CA: Elsevier Science.
  39. Altura BM, Altura BT, Carella A, et al. Alcohol produces spasms of human umbilical blood vessels: relationship to fetal alcohol syndrome (FAS). Eur J Pharmacol (1982) 86(2):311–312.[CrossRef][Web of Science][Medline]
  40. Goodlett CR, Horn KH, Zhou FC. Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exp Biol Med (Maywood) (2005) 230(6):394–406.[Abstract/Free Full Text]
  41. Feldman Y, Koren G, Mattice K, et al. Determinants of recall and recall bias in studying drug and chemical exposure in pregnancy. Teratology (1989) 40(1):37–45.[CrossRef][Web of Science][Medline]
  42. George L, Granath F, Johansson AL, et al. Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy. Acta Obstet Gynecol Scand (2006) 85(11):1331–1337.[Web of Science][Medline]
  43. deChazeron I, Liorca PM, Utghetto S, et al. Occult maternal exposure to environmental tobacco smoke exposure. Tob Control (2007) 16(1):64–65.[Abstract/Free Full Text]
  44. Roberts RJ. Can self-reported data accurately describe the prevalence of overweight? Public Health (1995) 109(4):275–284.[CrossRef][Web of Science][Medline]
  45. Nyholm M, Gullberg B, Merlo J, et al. The validity of obesity based on self-reported weight and height: implications for population studies. Obesity (Silver Spring) (2007) 15(1):197–208.[CrossRef][Medline]
  46. Khoury MJ, James LM, Flanders WD, et al. Interpretation of recurring weak associations obtained from epidemiologic studies of suspected human teratogens. Teratology (1992) 46(1):69–77.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
168/11/1259    most recent
kwn248v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Slickers, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Slickers, J. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?