Lorenzo D Botto

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

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Publications (127)730.78 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Typically gastroschisis is considered an isolated birth defect; however, other major malformations are reported to occur in 5-35% of cases depending on inclusion criteria. This study evaluated the associated malformations, small for gestational age, and survival among a clinically well-characterized population-based gastroschisis cohort, delivered from 1997-2011. We used data from Utah's statewide population-based surveillance system, which monitors major structural birth defects among all pregnancy outcomes (i.e., live births, stillbirths, pregnancy terminations, and miscarriages). Of the initial 387 gastroschisis cases, we excluded 51 (13.2%) for the following reasons: inadequately described or macerated fetuses, part of a specific malformation complex or sequence (limb-body wall complex, amniotic band sequence, or a severe form of abdominoschisis), leaving a study sample of 336 clinically confirmed cases. Gastroschisis was isolated non-syndromic in 284 cases (84.5%). One case was syndromic (trisomy 16; 0.3%) and the remaining 51 (15.2%) were classified as multiple: one unrelated major malformation (27; 52.9%); two or more unrelated major malformation or one major with multiple minor anomalies or mild malformations (6; 11.8%); ≥ one distinctive minor anomaly or mild malformation (13; 25.5%); amyoplasia (5; 1.5%). Of the liveborn infants, 63.3% were preterm (delivered at <37 weeks of gestation) and 21.8% were small for gestational age (SGA). SGA was more common in males (38.8%) than females (16%) (P = 0.008). Overall first year survival was high (95.6%); however, preterm infants with congenital intestinal atresia had the highest mortality (13.8%). The high proportion of isolated cases (84.5%) in gastroschisis is similar to that observed in many other phenotypes and not unique to gastroschisis. Because one in every six infants with gastroschisis had a major unrelated malformation, additional malformations should be sought in every newborn with gastroschisis. Infant mortality was low overall but still a significant concern in affected preterm infants with associated congenital intestinal atresia. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 10/2015; DOI:10.1002/ajmg.a.37437 · 2.16 Impact Factor
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    ABSTRACT: Objective: To investigate the association between Chlamydia trachomatis (CT) infection seropositivity and gastroschisis. Study design: In this case-control study we enrolled pregnant women either prenatally diagnosed with gastroschisis (cases, n=33) or with a normal ultrasound (controls, n=66). Both groups attended the University of Utah's Maternal Fetal Medicine Diagnostic Center for their diagnostic ultrasound or because of a community obstetrician referral. Participants completed a structured interview on potential risk factors. Anti-CT immunoglobulin (IgG)1 and IgG3 were measured by a CT elementary body enzyme-linked immunosorbent assay. Result: Median age at sexual debut was lower and reported sexual partner number higher in cases compared with controls. Risk factors for gastroschisis included having ⩾3 sexual partners (odds ratio (OR)=3.3, 95% CI 1.2, 9.4), change in partner from the previous pregnancy (OR=3.6, 95% CI 0.9, 13.9) and anti-CT IgG3 seropositivity (age-adjusted OR=3.9, 95% CI: 1.1, 13.2). Conclusion: Anti-CT IgG3 seropositivity was associated with greater than a threefold risk for gastroschisis.Journal of Perinatology advance online publication, 17 September 2015; doi:10.1038/jp.2015.115.
    Journal of perinatology: official journal of the California Perinatal Association 09/2015; DOI:10.1038/jp.2015.115 · 2.07 Impact Factor
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    ABSTRACT: Objective To evaluate whether better diet quality in mothers is associated with lower risk for major non-syndromic congenital heart defects in their children. Design Multicentre population-based case–control study, the National Birth Defects Prevention Study. Setting Ten sites in the USA. Participants Mothers of babies with major non-syndromic congenital heart defects (n=9885) and mothers with unaffected babies (n=9468) with estimated date of delivery from 1997 to 2009. Main outcome measures Adjusted ORs for specific major congenital heart defects by quartiles of maternal diet quality in the year before pregnancy, assessed by the Diet Quality Index for pregnancy (DQI-P) and the Mediterranean Diet Score. Quartile 1 (Q1) reflecting the worst diet quality and Q4 the best diet quality. Results Better diet quality was associated with reduced risk for some conotruncal and atrial septal heart defects. For DQI-P, estimated risks reductions (Q4 vs Q1) for conotruncal defects were 37% for tetralogy of Fallot (OR 0.63, 95% CI 0.49 to 0.80) and 24% overall (OR 0.76, 95% CI 0.64 to 0.91); and for septal defects, 23% for atrial septal defects (OR 0.77, 95% CI 0.63 to 0.94) and 14% overall (OR 0.86, 95% CI 0.75 to 1.00). Risk reductions were weaker or minimal for most other major congenital heart defects. Conclusions Better diet quality is associated with a reduced occurrence of some conotruncal and septal heart defects. This finding suggests that a reduction in certain cardiac malformations may be an additional benefit of improved maternal diet quality, reinforcing current preconception care recommendations.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 08/2015; DOI:10.1136/archdischild-2014-308013 · 3.12 Impact Factor
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    ABSTRACT: Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is being implemented in the United States and internationally; however, few data are available on the associated in-hospital costs and use of resources. Time and motion study in well-baby nurseries at two large urban hospitals in Utah using different approaches to pulse oximetry screening. Two observers recorded the time for each screening step together with provider and equipment characteristics. Structured questionnaire provided additional information on labor and equipment costs. Fifty-three CCHD screens were observed. At site A (n = 22), screening was mostly done by medical assistants (95%) using disposable probes (100%); at site B (n = 31), screening was mostly performed by certified nursing assistants (90%) using reusable probes (90%). Considering only first screens (n = 53), the median screen time was 8.6 min (range: 3.2-23.2), with no significant difference between sites. The overall cost ($ in 2014) of screening per baby was $24.52 at site A and $2.60 at site B. Nearly all the variation in cost (90%) was due to the cost of disposable probes; labor costs were similar between sites. CCHD screening by means of pulse oximetry is reasonably fast for most babies, leading to relative small labor costs with little variation by provider type. The main driver of costs is equipment: in a high throughput setting, reusable probes are currently associated with considerable cost saving compared with disposable probes. As programs expand to universal screening, improved and cheaper technologies could lead to considerable economies of scale. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 07/2015; DOI:10.1002/bdra.23414 · 2.09 Impact Factor
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    ABSTRACT: Background Congenital heart defects (CHDs) are the leading cause of infant death from birth defects. Animal studies suggest in utero alcohol exposure is a teratogen for cardiogenesis; however, results from epidemiologic studies are mixed.Methods Data from the National Birth Defects Prevention Study were used to estimate associations between CHDs and case (n = 7076) and control (n = 7972) mother reports of periconceptional (1 month before pregnancy through the first trimester) alcohol consumption with expected delivery dates during 1997 to 2007. CHDs were examined by category (conotruncal, septal, left ventricular outflow tract obstruction, and right ventricular outflow tract obstruction, heterotaxy with CHD) and subtype (e.g., tetralogy of Fallot [TOF]). Alcohol measures examined were any consumption, maximum average drinks per month, binge drinking, and alcohol type. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression analysis.ResultsIncreased risks, albeit marginally statistically significant, were observed for TOF and each maternal alcohol measure examined and for right ventricular outflow tract obstruction and heterotaxy with CHD and consumption of distilled spirits. Significantly reduced risks were observed for several CHD categories (septal defects, left ventricular outflow tract obstruction, and right ventricular outflow tract obstruction) and some corresponding subtypes with different alcohol measures. Significant risks were not observed for the other CHDs examined.Conclusion Analysis of this large, well-defined study sample did not show statistically significant increased risks between measures of maternal alcohol consumption and most CHDs examined. These findings may reflect, in part, limitations with retrospective exposure assessment or unmeasured confounders. Additional studies with continued improvement in measurement of alcohol consumption are recommended. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 06/2015; 103(7). DOI:10.1002/bdra.23352 · 2.09 Impact Factor
  • Marcia L Feldkamp · Lorenzo D Botto · John C Carey ·
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    ABSTRACT: Various experts in clinical teratology have proposed what they consider to be well-established teratogens. With the recent growth in the number of resources and investigations, there has been a notable proliferation of proposed risk factors as potential causes of human congenital structural defects. The purpose of this Commentary is to provide a concise summary of the current state of knowledge regarding known causes and environmental risk factors of structural defects. We performed a comprehensive search of PubMed for papers in English and in humans only, 2010 to 2014, that included birth defects, risk factors, and teratogens as key terms. Our search led to over 9000 papers dealing with these categories. From this, we were able to construct a timetable documenting the recognition of human teratogens and list several proposed environmental risk factors. Three relevant current trends were noticed: An increase of prescription and nonprescription medication use by women during pregnancy; the rise in obesity and its association with structural defects; and a growing body of work regarding outcomes associated with assisted reproductive technology. There are numerous risk factors, some modifiable, that have been proposed in recent years. These factors (associations) are only at the preliminary level in the causal chain and require replication. There is a need for more work on protective factors. The phenotypic characterization of cases with congenital defects has improved remarkably in recent years. However, there remains considerable concern with the precise characterization of exposures and the documentation of timing during embryologic development. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 06/2015; 103(8). DOI:10.1002/bdra.23392 · 2.09 Impact Factor
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    ABSTRACT: Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, but its causes are largely unknown. An increasing number of genes associated with congenital cerebellar malformations have been identified; however, few studies have examined the potential role of non-genetic, potentially modifiable risk factors. From the National Birth Defects Prevention Study, we examined maternal, paternal, and infant characteristics and maternal conditions and periconceptional exposures (from 1 month before to 3 months after conception) among infants with DWM (n = 160) and unaffected controls (n = 10,200), delivered between 1997 and 2009. Odds ratios, crude (cOR) and adjusted (aOR) were computed using logistic regression. Maternal factors associated with DWM included non-Hispanic black race/ethnicity (aOR = 2.0, 95%CI: 1.3-3.2). Among maternal conditions, a history of infertility increased the risk for DWM (all: aOR = 2.4, 95%CI: 1.3-4.6; multiple: aOR = 3.9, 95%CI: 1.7-8.9). The lack of association with many maternal exposures supports the hypothesis of a major contribution of genetic factors to the risk for DWM; however, the observed associations with maternal non-Hispanic black race/ethnicity and maternal history of infertility indicate that further research into factors underlying these characteristics may uncover potentially modifiable risk factors, acting alone or as a component of gene-environment interactions. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 05/2015; 167(9). DOI:10.1002/ajmg.a.37124 · 2.16 Impact Factor
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    L D Botto · A Correa · J D Erickson ·

  • H. Shanmugam · L. Brunelli · S. Krikov · L. Botto · M. Feldkamp ·

    Journal of Investigative Medicine 01/2015; 63(1):177-177. · 1.69 Impact Factor
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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.
    Journal of Nutrition 11/2014; 144(11):1781-6. DOI:10.3945/jn.114.201376 · 3.88 Impact Factor
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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 10/2014; 164(10). DOI:10.1002/ajmg.a.36695 · 2.16 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 Clinical and Molecular Teratology 09/2014; 100(9). DOI:10.1002/bdra.23247 · 2.09 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; 122(8). DOI:10.1289/ehp.1307289 · 7.98 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 04/2014; 210(4):359.e1–359.e11. DOI:10.1016/j.ajog.2013.10.880 · 4.70 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. DOI:10.1111/ppe.12093 · 3.13 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.
    Genetics in medicine: official journal of the American College of Medical Genetics 12/2013; 16(6). DOI:10.1038/gim.2013.177 · 7.33 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; 110(3). DOI:10.1016/j.ymgme.2013.08.020 · 2.63 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; 54(1). DOI:10.1111/head.12203 · 2.71 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 07/2013; 8(7):e69077. DOI:10.1371/journal.pone.0069077 · 3.23 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 12/2012; 94(12). DOI:10.1002/bdra.23103 · 2.09 Impact Factor

Publication Stats

6k Citations
730.78 Total Impact Points


  • 2006-2015
    • University of Utah
      • • Division of Medical Ethics
      • • Department of Pediatrics
      Salt Lake City, Utah, United States
  • 1996-2005
    • Centers for Disease Control and Prevention
      • • National Center on Birth Defects and Developmental Disabilities
      • • Division of Birth Defects and Developmental Disabilities
      • • National Center for Environmental Health
      Druid Hills, GA, United States
  • 2004
    • Instituto de Salud Carlos III
      • Center Congenital Anomalies Research (CIAC)
      Madrid, Madrid, Spain
  • 2003
    • Emory University
      Atlanta, Georgia, United States
  • 2001
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2000
    • Alessandra Lisi International Centre on Birth Defects and Prematurity
      Roma, Latium, Italy
  • 1992-1995
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 1993
    • Policlinico Universitario Agostino Gemelli
      Roma, Latium, Italy