Lorenzo D Botto

University of Utah, Salt Lake City, Utah, United States

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Publications (113)603.46 Total impact

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    ABSTRACT: Gastroschisis is unique because of its substantial risk in pregnancies of adolescent women. Adolescents may have poor diet quality, which places them at higher risk of gastroschisis.
    The Journal of nutrition. 11/2014; 144(11):1781-6.
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    ABSTRACT: Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0–1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non-white or younger than 20 years compared to white mothers or those age 25–29 years. The distribution of associated cardiac and extra-cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non-tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy-Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left-right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 08/2014; · 2.30 Impact Factor
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    ABSTRACT: Epidemiologic literature suggests exposure to air pollutants is associated with fetal development. To investigate maternal exposures to air pollutants during weeks two through eight of pregnancy and congenital heart defects. Mothers from the National Birth Defects Prevention Study, a nine-state case-control study, were assigned one-week and seven-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hour measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending upon the pollutant, a maximum of 4632 live-birth controls and 3328 live-birth, fetal-death or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics, tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context. Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the seven-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels. Utilizing daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy.
    Environmental Health Perspectives 04/2014; · 7.26 Impact Factor
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    ABSTRACT: BACKGROUND In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy-adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy-adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35) and all CHDs combined. Among CHD sub-types, we observed associations with left ventricular outflow tract obstruction defects, and its sub-type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01–2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09–1.87). CONCLUSION: Selected quartiles of energy-adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure-response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings. Birth Defects Research (Part A), 2014. © 2014 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 04/2014; · 2.27 Impact Factor
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    ABSTRACT: We investigated whether maternal exposure to cigarette smoke was associated with omphalocoele and whether periconceptional folic acid modified the association. : We analysed data from the National Birth Defects Prevention Study on omphalocoele case (n = 301) and control (n = 8135) mothers for infants born from 1997 through 2007. Mothers who reported active smoking or exposure to second-hand smoke during the periconceptional period (1 month before conception to 3 months after) were considered exposed. Those who reported use of folic acid supplements during the same period were considered supplement users. Odds ratios and 95% confidence intervals were estimated using multivariable logistic regression adjusted for alcohol use, preconception body mass index, and race/ethnicity. One hundred fifteen (38.2%) case and 2592 (31.9%) control mothers reported exposure to cigarette smoke during the periconceptional period. Adjusted odds ratios [95% confidence intervals] were 1.19 [0.94, 1.53] for any smoke exposure, 0.87 [0.54, 1.40] for active smoking, 1.38 [1.00, 1.90] for second-hand smoke exposure, and 1.16 [0.80, 1.67] for both exposures combined. No dose-response relationship was observed. Folic acid-containing supplements did not reduce the risk for omphalocoele among women with active or second-hand smoke exposure. Self-reported active maternal smoking, with or without exposure to second-hand smoke, during the periconceptional period was not associated with omphalocoele. In contrast, there was a possible association with periconceptional exposure to second-hand smoke.
    Paediatric and Perinatal Epidemiology 01/2014; 28(1):67-73. · 2.16 Impact Factor
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    ABSTRACT: Objective The purpose of this study was to evaluate whether maternal febrile illnesses in early pregnancy are associated with increased risk for congenital heart defects in the offspring and whether such risk is mitigated by multivitamin supplement use. Study Design From a multistate population-based case-control study (National Birth Defects Prevention Study), we compared maternal reports of first-trimester febrile illness from 7020 subjects with heart defects and 6746 unaffected control subjects who were born from 1997 through 2005. Relative risks were computed with no fever or infection during the first trimester as reference group and were adjusted for potential confounders. Results First-trimester febrile illness was reported by 7.4% of control mothers (1 in 13). Febrile genitourinary infections were associated with selected heart defects, particularly right-sided obstructive defects (odds ratios, >3) and possibly others, whereas common respiratory illnesses were associated with low-to-negligible risks for most heart defects. When risk estimates were elevated, they tended to be mitigated when multivitamin supplements had been taken in the periconceptional period. Conclusion The source of fever and the use of supplements appear to influence the risk for heart defects. This information can be helpful in counseling and research, in particular with regard to primary prevention.
    American journal of obstetrics and gynecology 01/2014; 210(4):359.e1–359.e11. · 3.28 Impact Factor
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    ABSTRACT: Purpose:The aim of this study was to describe the methods, cases, and initial results of a pilot project using existing public health data collection programs (birth defect surveillance or newborn screening) to conduct long-term follow-up of children with metabolic disorders.Methods:California, Iowa, New York, and Utah expanded birth defect surveillance or newborn screening programs to collect long-term follow-up data on 19 metabolic disorders. Data elements to monitor health status and services delivered were identified, and record abstraction and data linkages were conducted. Children were followed up through to the age of 3 years.Results:A total of 261 metabolic cases were diagnosed in 1,343,696 live births (19.4 cases/100,000; 95% confidence interval = 17.1-21.8). Four deaths were identified. Children with fatty acid oxidation disorders had a higher percentage of health service encounters compared with children with other disorders of at least one health service encounter (hospitalization, emergency room, metabolic clinic, genetic service provider, or social worker) except for hospitalizations; children with organic acid disorders had a higher percentage of at least one hospitalization during their third year of life than children with other disorders.Conclusion:Existing public health data programs can be leveraged to conduct population-based newborn screening long-term follow-up. This approach is flexible according to state needs and resources. These data will enable the states in assessing health burden, assuring access to services, and supporting policy development.Genet Med advance online publication 5 December 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.177.
    Genetics in medicine: official journal of the American College of Medical Genetics 12/2013; · 3.92 Impact Factor
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    ABSTRACT: Guanidinoacetate methyltransferase (GAMT) deficiency causes cerebral creatine deficiency. Patients can have autistic behavior, seizures, intellectual disability, and severe speech delay. The goal of therapy is to increase creatine while reducing potentially neurotoxic guanidinoacetate concentrations. Here we evaluate how different therapies affect plasma guanidinoacetate levels in patients with GAMT deficiency. Retrospective analysis of data from five new patients with GAMT deficiency (four with delays and seizures, one diagnosed at birth). The four symptomatic patients had decreased brain creatine by magnetic resonance spectroscopy and three also had abnormal globi pallidi by MRI. GAMT sequencing identified four previously reported mutations and one novel missense mutation (c.233T>A/p.V78E). Treatment with creatine (250-1000mg/kg/day), ornithine (100-800mg/kg/day), and sodium benzoate (50-135mg/kg/day) supplements along with dietary protein restriction (0.8-1.5g/kg/day) improved seizures and development with all patients becoming verbal. The patient treated at birth remains developmentally normal. Reduction in glycine and increase in ornithine levels significantly decreased plasma guanidinoacetate, with glycine levels being the best predictor of guanidinoacetate levels. In contrast, arginine levels were not significantly correlated with plasma guanidinoacetate. Our results show that supplements of creatine, sodium benzoate (to reduce glycine) and ornithine reduce guanidinoacetate levels in patients with GAMT deficiency (dietary therapy was not evaluated in our study). Normal development with early therapy renders GAMT deficiency an ideal candidate for inclusion in newborn screening panels.
    Molecular Genetics and Metabolism 09/2013; · 2.83 Impact Factor
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    ABSTRACT: Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension-type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity. To evaluate associations between butalbital and a wide range of specific birth defects. The National Birth Defects Prevention Study is an ongoing, case-control study of nonsyndromic, major birth defects conducted in 10 states. The detailed case classification and large number of cases in the National Birth Defects Prevention Study allowed us to examine the association between maternal self-reported butalbital use and specific birth defects. We conducted an analysis of 8373 unaffected controls and 21,090 case infants with estimated dates of delivery between 1997 and 2007; included were birth defects with 250 or more cases. An exploratory analysis examined groups with 100 to 249 cases. Seventy-three case mothers and 15 control mothers reported periconceptional butalbital use. Of 30 specific defect groups evaluated, adjusted odds ratios for maternal periconceptional butalbital use were statistically significant for 3 congenital heart defects: tetralogy of Fallot (adjusted odds ratio = 3.04; 95% confidence interval = 1.07-8.62), pulmonary valve stenosis (adjusted odds ratio = 5.73; 95% confidence interval = 2.25-14.62), and secundum-type atrial septal defect (adjusted odds ratio = 3.06; 95% confidence interval = 1.07-8.79). In the exploratory analysis, an elevated odds ratio was detected for 1 congenital heart defect, single ventricle. We observed relationships between maternal periconceptional butalbital use and certain congenital heart defects. These associations have not been reported before, and some may be spurious. Butalbital use was rare and despite the large size of the National Birth Defects Prevention Study, the number of exposed case and control infants was small. However, if confirmed in additional studies, our findings will be useful in weighing the risks and benefits of butalbital for the treatment of migraine and tension-type headaches.
    Headache The Journal of Head and Face Pain 09/2013; · 2.94 Impact Factor
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    ABSTRACT: Birth defects are an increasing health priority worldwide, and the subject of a major 2010 World Health Assembly Resolution. Excess cancer risk may be an added burden in this vulnerable group of children, but studies to date have provided inconsistent findings. This study assessed the risk for cancer in children and young adolescents with major birth defects. This retrospective, statewide, population-based, cohort study was conducted in three US states (Utah, Arizona, Iowa). A cohort of 44,151 children and young adolescents (0 through 14 years of age) with selected major, non-chromosomal birth defects or chromosomal anomalies was compared to a reference cohort of 147,940 children without birth defects randomly sampled from each state's births and frequency matched by year of birth. The primary outcome was rate of cancer prior to age 15 years, by type of cancer and type of birth defect. The incidence of cancer was increased 2.9-fold (95% CI, 2.3 to 3.7) in children with birth defects (123 cases of cancer) compared to the reference cohort; the incidence rates were 33.8 and 11.7 per 100,000 person-years, respectively. However, the excess risk varied markedly by type of birth defect. Increased risks were seen in children with microcephaly, cleft palate, and selected eye, cardiac, and renal defects. Cancer risk was not increased with many common birth defects, including hypospadias, cleft lip with or without cleft palate, or hydrocephalus. Children with some structural, non-chromosomal birth defects, but not others, have a moderately increased risk for childhood cancer. Information on such selective risk can promote more effective clinical evaluation, counseling, and research.
    PLoS ONE 01/2013; 8(7):e69077. · 3.53 Impact Factor
  • Birth Defects Research Part A Clinical and Molecular Teratology 12/2012; 94(12):970-83. · 2.27 Impact Factor
  • Richard S Olney, Lorenzo D Botto
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    ABSTRACT: Newborn screening for critical congenital heart defects, added in September 2011 to the Recommended Uniform Screening Panel in the United States, is a new public health priority and has particular relevance for state birth defects surveillance programs. In this commentary, we review the background to potential involvement by birth defects programs with screening, and detail key questions that these programs can evaluate: (1) health outcomes after newborn screening among affected children; (2) missed primary targets of screening (i.e., affected children who were not screened or had false-negative screens); (3) burden and screening accuracy for secondary targets; (4) the role of altitude, sociodemographic characteristics, and other special circumstances; (5) the contribution of prenatal and clinical diagnoses before newborn screening; and (6) costs and service utilization. To address these issues, monitoring programs will need to pay particular attention to: (1) data sources and quality; (2) timeliness; (3) long-term follow-up for comprehensive outcomes; (4) reporting standards; and (5) state and national program coordination. Although some aspects of involvement with these screening programs will require new partnerships and paradigm shifts in birth defects program operations, the visibility of these screening programs among stakeholders will also provide birth defects programs with new opportunities to demonstrate their usefulness. Birth Defects Research (Part A), © 2012 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 11/2012; · 2.27 Impact Factor
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    ABSTRACT: Although the descriptive epidemiology of atrioventricular septal defects (AVSDs), a group of serious congenital heart defects (CHDs), has been recently reported, non-genetic risk factors have not been consistently identified. Using data (1997-2005) from the National Birth Defects Prevention Study, an ongoing multisite population-based case-control study, the association between selected non-genetic factors and non-syndromic AVSDs was examined. Data on periconceptional exposures to such factors were collected by telephone interview from 187 mothers of AVSD case infants and 6,703 mothers of unaffected infants. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Mothers who reported cigarette smoking during the periconceptional period were more likely to have infants with AVSDs compared with non-smokers, independent of maternal age, periconceptional alcohol consumption, infant gestational age, family history of CHDs, and study site (aOR 1.5, 95% CI 1.1-2.4). The association was strongest in mothers who smoked more than 25 cigarettes/day. In addition, mothers with periconceptional passive smoke exposure were more likely to have infants with AVSDs than unexposed mothers, independent of maternal age, active periconceptional smoking, infant gestational age, and family history of CHDs (aOR 1.4, 95% CI 1.0-2.0). No associations were observed between AVSDs and maternal history of a urinary tract infection or pelvic inflammatory disease, maternal use of a wide variety of medications, maternal occupational exposure, parental drug use, or maternal alcohol consumption. If the results of this preliminary study can be replicated, minimizing maternal active and passive smoke exposure may decrease the incidence of AVSDs. © 2012 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 08/2012; 158A(10):2447-2455. · 2.30 Impact Factor
  • Marcia L Feldkamp, Neil E Bowles, Lorenzo D Botto
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    ABSTRACT: The AEBP1 (adipocyte enhancer binding protein) gene has two isoforms: AEBP1, the shorter of the two isoforms, and Aclp (aortic carboxypeptidase-like protein). Aclp(-/-) mice demonstrate a ventral wall defect that is similar to gastroschisis in humans. Aclp is a potential candidate gene because it is expressed in numerous tissues during early development in mice; it associates with the extracellular matrix; and is essential for abdominal wall development and wound healing. In contrast, AEBP1 encodes an intracellular protein involved in proinflammatory responses, and may play a critical role in apoptosis and cell survival. Gastroschisis is a severe abdominal wall defect more common in young women and recently associated with a genitourinary infection early in pregnancy. We screened AEBP1 in 40 cases of gastroschisis and compared identified variants in a control population. We identified several novel variants in AEBP1, including synonymous and nonsynonymous single nucleotide substitutions and intronic indels. However, the frequency of these variants was not significantly different from that of the control group, and the associated amino acid changes were predicted to be benign by two prediction software programs. Gastroschisis remains an intriguing defect that, for an unknown reason, occurs more commonly in young women and after a genitourinary infection. Although we found many alterations in AEBP1 among the gastroschisis cases, they were predicted to be benign. However, this gene requires further understanding of its interaction with other genes involved in the immune response pathway. Birth Defects Research (Part A) 94:738-742, 2012. © 2012 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 07/2012; 94(9):738-42. · 2.27 Impact Factor
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    ABSTRACT: We examined whether hypospadias was associated with several aspects of the diet, including intake of animal products, intake of several nutrients and food groups related to a vegetarian diet and oestrogen metabolism, and diet quality. The study included deliveries from 1997 to 2005 that were part of the National Birth Defects Prevention Study. Diet was assessed by food frequency questionnaire during maternal telephone interviews, and two diet quality indices were developed based on existing indices. Analyses included 1250 cases with second- or third-degree hypospadias (urethra opened at the penile shaft, scrotum or perineum) and 3118 male, liveborn, non-malformed controls. All odds ratios (OR) and 95% confidence intervals [CI] were estimated from logistic regression models that included several potential confounders, including energy intake. Intake of animal products was not associated with hypospadias; for example, the adjusted OR for any vs. no intake of meat was 1.0 [95% CI 0.6, 1.6]. Frequency of intake of meat or other animal products was also not associated with hypospadias, nor was intake of iron or several nutrients that are potentially related to oestrogen metabolism. Diet quality was also not associated with hypospadias; the OR for diet quality in the highest vs. lowest quartile for the two diet quality indices were 1.0 [95% CI 0.6, 1.6] and 0.9 [95% CI 0.7, 1.1]. This large study does not support an association of a vegetarian diet or worse diet quality with hypospadias.
    Paediatric and Perinatal Epidemiology 07/2012; 26(4):353-60. · 2.16 Impact Factor
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    ABSTRACT: Glutaric acidemia type 1 (GA-1) is an autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism. Patients may present with brain atrophy, macrocephaly, and acute dystonia secondary to striatal degeneration typically triggered by an infection, fever, and/or dehydration. This disorder is identified on expanded newborn screening by increased glutarylcarnitine. We evaluated the outcome of 19 patients with GA-1. Ten patients were diagnosed by newborn screening and 9 were diagnosed clinically. DNA testing in 12 patients identified 15 different mutations in the glutaryl-CoA dehydrogenase gene. Plasma glutarylcarnitine and urinary 3-hydroxyglutaric acid were elevated in all patients. However, only 10 of 17 patients who underwent urine organic acid analysis were high excretors of glutaric acid. Levels of glutarylcarnitine in plasma correlated with the urinary excretion of glutaric and 3-hydroxyglutaric acid, but not with clinical outcome. Plasma lysine was also significantly correlated with urinary glutaric acid, but not with urinary 3-hydroxyglutaric acid. Brain magnetic resonance imaging in all patients showed wide Sylvian fissures before treatment, which normalized by 4 years of age in treated patients. The occurrence of three adverse outcomes (oral motor function, ambulatory capability, and dystonic movements) was on average reduced by 75% (relative risk 0.25 to 0.28) in patients identified by newborn screening compared to patients diagnosed before newborn screening (Fisher's exact test; p=0.0055 for oral motor function and ambulatory capability; p=0.023 for dystonic movements). Newborn screening is effective in the prevention of complications in patients with GA-1 when coupled with treatment strategies.
    Molecular Genetics and Metabolism 06/2012; 106(4):430-8. · 2.83 Impact Factor
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    ABSTRACT: The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus.
    American journal of obstetrics and gynecology 03/2012; 206(3):218.e1-13. · 3.28 Impact Factor
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    ABSTRACT: To examine whether better maternal diet quality was associated with reduced risk for selected birth defects. A multicenter, population-based case-control study, the National Birth Defects Prevention Study. Ten participating centers in the United States. Eligible subjects' estimated due dates were from October 1997 through December 2005. Telephone interviews were conducted with 72% of case and 67% of control mothers. Analyses included 936 cases with neural tube defects (NTDs), 2475 with orofacial clefts, and 6147 nonmalformed controls. Food-frequency data were used to calculate the Mediterranean Diet Score (MDS) and Diet Quality Index (DQI), modeled after existing indices. Adjusted odds ratios (ORs). After covariate adjustment, increasing diet quality based on either index was associated with reduced risks for the birth defects studied. The strongest association was between anencephaly and DQI; the OR for highest vs lowest quartile was 0.49 (95% CI, 0.31-0.75). The ORs for cleft lip with or without cleft palate and cleft palate and DQI were also notable (0.66 [95% CI, 0.54-0.81] and 0.74 [95%CI, 0.56-0.96], respectively). Healthier maternal dietary patterns, as measured by diet quality scores, were associated with reduced risks of NTDs and clefts. These results suggest that dietary approaches could lead to further reduction in risks of major birth defects and complement existing efforts to fortify foods and encourage periconceptional multivitamin use.
    JAMA Pediatrics 02/2012; 166(2):121-6. · 4.28 Impact Factor
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    ABSTRACT: Cloacal exstrophy presents as a complex abdominal wall defect thought to result from a mesodermal abnormality. Anatomically, its main components are Omphalocele, bladder Exstrophy and Imperforate anus. Other associated malformations include renal malformations and Spine defects (OEIS complex). Historically, the prevalence ranges from 1 in 200,000 to 400,000 births, with higher rates in females. Cloacal exstrophy is likely etiologically heterogeneous as suggested by its recurrence in families and occurrence in monozygotic twins. The defect has been described in infants with limb-body wall, with trisomy 18, and in one pregnancy exposed to Dilantin and diazepam. Due to its rarity, the use of a nonspecific diagnostic code for case identification, and lack of validation of the clinical findings, cloacal exstrophy remains an epidemiologic challenge. The purpose of this study was to describe the prevalence, associated anomalies and maternal characteristics among infants born with cloacal exstrophy. We used data from the International Clearinghouse for Birth Defects Surveillance and Research submitted from 18 birth defect surveillance programs representing 24 countries. Cases were clinically evaluated locally and reviewed centrally by two authors. Cases of persistent cloaca were excluded. A total of 186 cases of cloacal exstrophy were identified. Overall prevalence was 1 in 131,579 births: ranging from 1 in 44,444 births in Wales to 1 in 269,464 births in South America. Live birth prevalence was 1 in 184,195 births. Prevalence ratios did not vary by maternal age. Forty-two (22.6%) cases met the criteria for the OEIS complex, whereas 60 (32.3%) were classified as OEI and 18 (9.7%) as EIS (one with suspected VATER (0.5%)). Other findings included two cases with trisomy 13 (one without a karyotype confirmation), one with mosaic trisomy 12 (0.5%), one with mosaic 45,X (0.5%) and one classified as having amnion band sequence (0.5%). Twenty-seven (14.5%) infants had other anomalies unrelated to cloacal exstrophy. Cloacal exstrophy is a rare anomaly with variability in prevalence by geographic location. The proportion of cases classified as OEIS complex was lower in this study than previously reported. Among all cases, 54.8% were reported to have an omphalocele.
    American Journal of Medical Genetics Part C Seminars in Medical Genetics 11/2011; 157C(4):333-43. · 4.44 Impact Factor
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    ABSTRACT: Sirenomelia is a very rare limb anomaly in which the normally paired lower limbs are replaced by a single midline limb. This study describes the prevalence, associated malformations, and maternal characteristics among cases with sirenomelia. Data originated from 19 birth defect surveillance system members of the International Clearinghouse for Birth Defects Surveillance and Research, and were reported according to a single pre-established protocol. Cases were clinically evaluated locally and reviewed centrally. A total of 249 cases with sirenomelia were identified among 25,290,172 births, for a prevalence of 0.98 per 100,000, with higher prevalence in the Mexican registry. An increase of sirenomelia prevalence with maternal age less than 20 years was statistically significant. The proportion of twinning was 9%, higher than the 1% expected. Sex was ambiguous in 47% of cases, and no different from expectation in the rest. The proportion of cases born alive, premature, and weighting less than 2,500 g were 47%, 71.2%, and 88.2%, respectively. Half of the cases with sirenomelia also presented with genital, large bowel, and urinary defects. About 10-15% of the cases had lower spinal column defects, single or anomalous umbilical artery, upper limb, cardiac, and central nervous system defects. There was a greater than expected association of sirenomelia with other very rare defects such as bladder exstrophy, cyclopia/holoprosencephaly, and acardia-acephalus. The application of the new biological network analysis approach, including molecular results, to these associated very rare diseases is suggested for future studies.
    American Journal of Medical Genetics Part C Seminars in Medical Genetics 11/2011; 157C(4):358-73. · 4.44 Impact Factor

Publication Stats

4k Citations
603.46 Total Impact Points

Institutions

  • 2007–2014
    • University of Utah
      • • Department of Pediatrics
      • • Division of Medical Ethics
      Salt Lake City, Utah, United States
  • 2012
    • University of Iowa
      • Department of Pediatrics
      Iowa City, IA, United States
  • 1993–2012
    • Centers for Disease Control and Prevention
      • • National Center on Birth Defects and Developmental Disabilities
      • • Division of Birth Defects and Developmental Disabilities
      Druid Hills, GA, United States
    • Policlinico Universitario Agostino Gemelli
      Roma, Latium, Italy
    • University of Ferrara
      Ferrare, Emilia-Romagna, Italy
  • 2010
    • University of Padova
      • Department of Pediatrics
      Padova, Veneto, Italy
  • 2000–2010
    • Alessandra Lisi International Centre on Birth Defects and Prematurity
      Roma, Latium, Italy
  • 2004
    • Instituto de Salud Carlos III
      • Center Congenital Anomalies Research (CIAC)
      Madrid, Madrid, Spain
  • 2002
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 1992–1994
    • The Catholic University of America
      Washington, Washington, D.C., United States