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C A Loffredo

Publications and source records attributed to C A Loffredo.

15 recordsLinked to original sources
PubMed2001

Association of transposition of the great arteries in infants with maternal exposures to herbicides and rodenticides.

The Baltimore-Washington Infant Study, a case-control study of congenital heart defects in liveborn infants conducted in 1981--1989, interviewed parents about a wide range of environmental exposures that occurred during and before the pregnancy. In the period 1987--1989, the questionnaire was expanded to include a detailed inquiry about exposures to pesticides. An analysis of these latter data revealed an association of maternal exposure to any pesticides during the first trimester with transposition of the great arteries in their infants (TGA; n = 66 infants), relative to 771 control infants, with an odds ratio of 2.0 (95% confidence interval (CI): 1.2, 3.3). No other heart defects were associated with pesticides. When analyzed by type of pesticide and adjusted for covariates, there were associations of TGA with maternal exposures to herbicides (odds ratio (OR) = 2.8; 95% CI: 1.3, 7.2) and to rodenticidal chemicals (OR = 4.7; 95% CI: 1.4, 12.1) but not to insecticides (OR = 1.5; 95% CI: 0.9, 2.6). No data were collected on specific chemicals or brand names. These results raise new questions about the possible epidemiologic association of TGA with some classes of pesticides and warrant new, carefully targeted investigations.

Adult↗
PubMed2001

Atrioventricular septal defects: possible etiologic differences between complete and partial defects.

BACKGROUND: Recent advances in clinical, pathological, and genetic aspects of atrioventricular septal defects (AVSD) have set the stage for epidemiologic investigations into possible risk factors. Previous analyses of the total case group of AVSD included complete and partial subtypes without analysis of the subsets. METHODS: To address the question of possible morphogenetic heterogeneity of AVSD, the Baltimore-Washington Infant Study data on live-born cases and controls (1981-1989) was reanalyzed for potential environmental and genetic risk-factor associations in complete AVSD (n = 213), with separate comparisons to the atrial (n = 75) and the ventricular (n = 32) forms of partial AVSD. RESULTS: Complete and ventricular forms of AVSD had a similar proportion of isolated cases (12.2% and 15.6%, respectively, without associated extracardiac anomalies) and high rates of Down syndrome, whereas the atrial form of partial AVSD included 55% isolated cases. Trisomy 18 occurred in 22% of infants with the ventricular form, compared with <2% in the other AVSD groups. Analysis of potential risk factors revealed further distinctions. Complete AVSD as an isolated cardiac defect was strongly associated with maternal diabetes (odds ratio [OR] = 20.6; 95% confidence interval [CI] =5.6-76.4) and also with antitussive use (OR = 8.8; CI = 1.2-48.2); there were no strong associations other than maternal age among Down syndrome infants with this type of heart defect. Isolated cases with the atrial type of partial AVSD were associated with a family history of heart defects (OR = 6.2; CI = 1.4-24.4) and with paternal occupational exposures to ionizing radiation (OR = 5.1; CI = 1.4-27.4), but no risk factors were associated with Down syndrome. There were no significant associations of any risk factors in the numerically small subsets of isolated and Down syndrome cases with the ventricular form of partial AVSD. CONCLUSIONS: These results indicate a similar risk profile of complete AVSD and the ventricular type of partial AVSD, with a possible subset of the latter due to trisomy 18. Maternal diabetes constituted a potentially preventable risk factor for the most severe, complete form of AVSD.

Adult↗
PubMed2001

Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants.

BACKGROUND: Intensive medical care of women with diabetes has reduced their risks of bearing infants with congenital anomalies. To assess the preventive potential of preconceptional care, the data of a population-based study of cardiovascular malformations (CVM) were analyzed to determine the morphogenetic specificity of maternal diabetes risks, the morbidity and mortality of the infants, and maternal characteristics that might affect these risks. METHODS: The Baltimore-Washington Infant Study was a case-control study (1981-1989) that included all live born infants with confirmed CVM; control infants were a representative sample of the birth cohort. A questionnaire administered in home visits recorded parental information on social, medical, occupational, and environmental factors. For these analyses of preconceptional diabetes risks, the case group excluded chromosomal and mendelian disorders and was divided into 3 developmental categories and 12 diagnostic groups. RESULTS: Preconceptional maternal diabetes was strongly associated with CVM of early embryonic origin (odds ratio [OR] = 4.7, 95% confidence interval [CI] 2.8-7.9) and with cardiomyopathy (OR = 15.1, 95% CI 5.5-41.3), but not with obstructive and shunting defects (OR = 1.4, 95% CI 0.7-3.0). There was heterogeneity within these developmental categories: among laterality defects, diabetes was associated only with cardiovisceral and atrioventricular discordance (OR = 10.0, 95% CI 3.7-27.0); among outflow tract anomalies, the risk was strongly associated with normally related great arteries (OR = 6.6, 95% CI 3.2-13.3) but not with simple transpositions; and among atrioventricular septal defects, diabetes was associated with the complete but not with the partial forms (OR = 22.8, 95% CI 7.4-70.5). The association in early CVM was strongest among infants with multisystem, predominantly VACTERL, anomalies. All-cause mortality of infants with CVM was 39% among those with diabetic mothers and 17.8% in those with nondiabetic mothers. Deceased infants of diabetic mothers were also more likely to have extracardiac anomalies (P = 0.041), to be born prematurely (P = 0.007), and to have low birth weight (P = 0.011). Multivariate analyses of maternal factors revealed no significant confounders of the diabetes associations. CONCLUSIONS: The evidence of diabetes-induced major cardiac defects is of urgent clinical significance. The effectiveness of early preconceptional care in the prevention of congenital anomalies has been demonstrated repeatedly.

Adult↗
PubMed2001

A population-based study of coarctation of the aorta: comparisons of infants with and without associated ventricular septal defect.

BACKGROUND: Coarctation of the aorta (CoA) is a congenital cardiovascular malformation (CCVM) sometimes associated with ventricular septal defect (VSD). Although the phenotypic association is well documented, little research exists on the epidemiological features distinguishing CoA with and without VSD. METHODS: The Baltimore-Washington Infant Study (1981-1989), a population-based study of CCVM, evaluated 126 infants with "pure" CoA (free of associated cardiac defects) and 67 infants with CoA and VSD (COA/VSD) in comparison to 3,572 controls. RESULTS: The proportion of infants with associated extracardiac anomalies was greater among CoA/VSD than among pure CoA (31% versus 11%). Infants with CoA/VSD were twice as likely as those with pure CoA to be born small for gestational age (23% versus 12%, respectively, compared with 6% of controls). All-cause mortality during the first year of life was higher in CoA/VSD than in pure CoA (21% vs. 7%). Multiple logistic regression models revealed that family history of CCVM was associated with pure CoA (adjusted case-control odds ratio [OR] = 4.6; 99% confidence interval [CI] = 1.5-13.9) and with CoA/VSD (OR = 5.9, CI = 1.2-23.5); maternal history of organic solvent exposures early in pregnancy was also associated with pure CoA (OR = 3.2, CI = 1.0-10.2) and with CoA/VSD (OR = 3.7, CI 0.9-14.9). Additional risk factors, including maternal epilepsy (OR = 5.3, CI = 0.9-30.6), and use of macrodantin (OR = 6.7, CI = 1.4-31.8) were associated only with pure CoA. CONCLUSIONS: These findings highlight possible genetic and environmental differences between pure CoA and CoA/VSD and may stimulate further investigations of the etiology of CoA.

Age Factors↗
PubMed2000

Interrupted aortic arch: an epidemiologic study.

BACKGROUND: Interruption of the aortic arch (IAA) is a rare but severe anomaly associated with major intracardiac defects and with multisystem noncardiac malformations, recently linked to chromosome deletion of 22q11.2. METHODS: The Baltimore-Washington Infant Study (1981-1989), a population-based epidemiologic study of cardiovascular malformations, evaluated 53 infants with IAA in comparison with 3,572 controls. Risk factors for the anatomic subtypes were evaluated in 14 cases of IAA type A and 32 cases of IAA type B, but no molecular genetic tests were available. The distribution of associated cardiac defects was similar for both types. RESULTS: DiGeorge syndrome (DGS) occurred more frequently in IAA type B. Case-control comparisons demonstrated that infants in both groups were growth retarded at birth. A family history of noncardiac defects occurred only in IAA type B cases and included relatives with cleft lip and/or cleft palate. Candidate risk factors were associated only in type B cases and differed for those with (n = 10) and for those without (n = 19) DGS: a family history of noncardiac defects (odds ratio [OR] = 7.2, 95% confidence interval [CI] = 1.5-39.2) and maternal use of aspirin during the critical period (OR = 4.8, 95% CI = 1.3-25.4) occurred with DGS, while previous stillbirth (OR = 9.4, 95% CI = 1.3-53.1), bleeding during pregnancy (OR = 3.7, 95% CI = 1.4-11.4), and maternal exposure to arts/crafts paints (OR = 4.8, 95% CI = 1.3-17.4) were associated in those without DGS. CONCLUSIONS: These findings confirm the heterogeneity of IAA and of the type B subtype. Risk factors specific for cases with DGS may open a window to further investigations of the etiology of IAA and of the associated molecular genetic abnormalities.

Abnormalities, Multiple↗
PubMed2000

Epidemiology of cardiovascular malformations: prevalence and risk factors.

Epidemiological approaches to the study of cardiovascular malformations (CVMs) face challenges of disease definition, nomenclature, changing diagnostic methodologies, the rarity of the disease in the general population, and the incorporation of current knowledge on genetics and morphogenesis into designing studies to investigate risk factors and implement preventive strategies. Previous studies, especially the population-based Baltimore-Washington Infant Study, have documented variability in the prevalence of specific types of CVM by time, place, and personal characteristics and have highlighted the potential prevention of diabetes-associated heart malformations through timely medical management of pre-conception diabetes. Left-sided obstructive heart defects have been identified as targets for new studies of genetic risk factors. Potential environmental risk factors for CVMs also have been identified, such as organic solvents and pesticides, coincident with the emergence of new strategies to study genetic susceptibility and gene-environment interactions. Increased collaborative, multicenter research on these and other factors, such as nutritional factors in early pregnancy, offers new hope for potentially reducing the burden of CVM in the population.

Abnormalities, Drug-Induced↗
PubMed1999

Failure to diagnose congenital heart disease in infancy.

OBJECTIVE: To identify factors that predict failure to diagnose congenital heart disease in newborns. DESIGN: All fatal cases in the Baltimore-Washington Infant Study were compiled. The Baltimore-Washington Infant Study includes 4390 cases of infants with congenital cardiovascular malformations identified in a population-based study between 1981 and 1989 in the Baltimore-Washington metropolitan area. Death occurred in 800 such infants in the first year of life. In 76 of these infants, death occurred before diagnosis of heart disease. These cases were identified by community search of autopsy records. Their characteristics are compared with those of infants who died after a cardiac diagnosis was made. RESULTS: Infant characteristics (birth weight, gestational age, intrauterine growth retardation, and chromosomal anomaly) are associated with death of infants with congenital cardiovascular malformations and with death of such infants before diagnosis. Diagnoses of coarctation of the aorta, Ebstein's anomaly, atrial septal defect, and truncus arteriosus are overrepresented in infants found by community search, particularly in those infants without associated malformations. Paternal education is associated with failure to diagnose congenital heart disease in life but other sociodemographic characteristics of the infant's family are not. CONCLUSIONS: Diagnosis of congenital cardiovascular malformations requires close observation in the neonatal period. Analysis of age at death of infants with undiagnosed congenital cardiovascular malformation suggests that such infants may be at risk if discharged within the first 2 days of life.

Age Distribution↗
PubMed1998

Attributable fraction for cardiac malformations.

To the authors' knowledge, attributable fractions for cardiac malformations have not been reported before. The Baltimore-Washington Infant Study published factors associated with several major cardiac malformations in Maryland, the District of Columbia, and adjacent counties of northern Virginia in 1981-1989. For eight of these malformations, the authors provide attributable fractions of those factors that are potentially causal. Summary attributable fractions range from 13.6% (four factors) for hypoplastic left heart to 30.2% (seven factors) for transposition of great arteries with intact ventricular septum. Extra attributable fraction for factor x, defined as summary attributable fraction for all factors minus that for all but x, is largest for: 1) paternal marijuana use in transposition of great arteries with intact ventricular septum, 7.8%; 2) paternal anesthesia in tetralogy of Fallot, 3.6%; 3) painting in atrioventricular septal defect with Down syndrome, 5.1 %; 4) solvent/degreasing agent exposure in hypoplastic left heart, 4.6%; 5) sympathomimetics in coarctation of aorta, 5.8%; 6) pesticide exposure in isolated membranous ventricular septal defect, 5.5%; 7) hair dye in multiple/multiplex membranous ventricular septal defect, 3.3%; and 8) urinary tract infection in atrial septal defect, 6.4%. Percent-of-cases-exposed dominates relative risk in attributable fraction. If these factors are causal, the larger extra attributable fractions suggest the potential for prevention by specific interventions before/during pregnancy.

Case-Control Studies↗
PubMed1998

Preconceptional folate intake and malformations of the cardiac outflow tract. Baltimore-Washington Infant Study Group.

We compared cases with outflow tract defects (N = 126) with controls representative of the same birth cohort (N = 679). Infants with clinically recognized syndromes were excluded. Daily total maternal folate intake of > or =245 microg was inversely related to risk of cardiac outflow tract defects among those with transposition (odds ratio estimates: 0.65, 0.78, and 0.76 with increasing quartile of daily folate intake), but positively related among those with normally related vessels (corresponding odds ratio estimates: 1.18, 1.59, and 1.68). This difference disappeared when maternal intake of supplemental folic acid of > or =400 microg compared with <400 microg was considered, excluding dietary intake [odds ratio (OR) = 1.04; 95% confidence interval (CI) = 0.5-2.2 for infants with transposition, and OR = 0.91; 95% CI = 0.5-1.8 for those without transposition of the great arteries].

Dietary Supplements↗
PubMed1997

Paternal risk factors for isolated membranous ventricular septal defects.

A case-control study using data from the Baltimore-Washington Infant Study (BWIS) examined possible paternal risk factors in the etiology of isolated membranous ventricular septal defects (VSD). There were 641 total VSD case infants and 3,549 randomly selected control infants ascertained between 1981 and 1989. Isolated membranous VSDs were identified in 499 cases. Socio-demographic factors (such as parental age and race), social habits, and medical conditions were analyzed by multiple logistic regression in order to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Paternal age was not found to be a risk factor per se, but small positive associations were found for some social habits and maternal factors. Significant associations were found for paternal marijuana use (OR 1.36, 95% CI 1.05-1.76), African-American race of the infant (OR 1.34, 95% CI 1.09-1.65), and for cocaine use among older fathers (OR 3.92, 95% CI 1.30-11.86). These associations support a multifactorial etiologic hypothesis for isolated membranous VSDs and point to some interesting parental behavioral and medical considerations which may contribute to risk for this common birth defect.

Adult↗
PubMed1997

Use of stored newborn blood spots in research on birth defects: variation in retrieval rates by type of defect and infant characteristics.

Stored blood spots from state newborn screening programs represent a potential source of DNA for molecular genetics research on birth defects. The stored blood spots of cases and controls from an epidemiologic database on congenital heart defects were sought in the present study, which aimed to establish the feasibility of linking the data sources and to examine blood spot retrieval rates for selected cardiac defects. Blood spots were located on 341 of 522 infants (65%) with congenital heart defects and for 1,484 of 1,645 infants without birth defects (84%) born in Maryland during 1981-1989. Retrieval rates were low among infants with clinically severe lesions such as truncus arteriosus (26%) but were considerably higher in infants with coarctation of the aorta (62%), pulmonic valve stenosis (71%), and atrial septal defect (76%). Retrieval rates were significantly lower for premature and low-birth-weight infants than among full-term, normal-birth-weight infants. Retrieval rates did not vary significantly by gender, race, county of residence, or parental socioeconomic characteristics. These results demonstrate the feasibility of linking epidemiologic databases with stored newborn blood specimens, especially for normal infants and even for infants with certain congenital heart defects, but raise concerns about the adequacy of such methods to obtain stored specimens from premature infants and from those with severe heart defects.

Female↗
PubMed1995

Non-cardiac malformations in individuals with outflow tract defects of the heart: the Baltimore-Washington Infant Study (1981-1989).

In the Baltimore-Washington Infant Study, a regional case-control study of 4,390 liveborn infants with cardiovascular malformations (CVM), 642 patients (14.2%) had outflow tract abnormalities, with extracardiac defects in 157 (approximately 25%) of them. Associated defects were found in 1/3 of patients with normal great arteries, but only in 1/10 of patients with transposition of great arteries (TGA). The extracardiac defects were especially rare in the groups "TGA with intact ventricular septum" and "TGA with ventricular septal defect". Patients with multiple associated defects outnumbered patients with isolated associated defects in the ratio 2.5:1. The associated defects were heterogeneous: 46 patients had chromosome abnormalities, 16 had different Mendelian syndromes, and 36 had associations (DiGeorge sequence and VACTERL association were the most frequent). A new syndrome of multiple congenital abnormalities including tetralogy of Fallot, and rare cases of chromosomal and Mendelian syndromes (distal trisomy 1q, tetrasomy 8p, Holzgreve syndrome) are described briefly. Sufficient variability of a spectrum of conotruncal defects in the patients with the same chromosomal or Mendelian syndromes suggests that at least in some cases different conotruncal defects are stages of the same morphologic spectrum. The analysis of conotruncal defects in sibs of patients with Mendelian syndromes may provide new data about the links between different definitive forms of CVM.

Abnormalities, Multiple↗
PubMed1993

Temporal trends in prevalence of cardiovascular malformations in Maryland and the District of Columbia, 1981-1988. The Baltimore-Washington Infant Study Group.

We studied the yearly occurrence of isolated cardiovascular malformations in liveborns for the period 1981-1988 in Maryland and the District of Columbia. We used Poisson regression to fit yearly prevalence at birth as a function of time for all cardiovascular malformation case types combined and for three diagnostic subgroups. We give results separately by diagnostic method and race (white/nonwhite), with categories combined when appropriate. Time trends were similar for both races except in pulmonic stenosis diagnosed by echocardiography. The yearly prevalence for all case types, all races, and all diagnostic methods combined increased from 28 to 43 per 10,000 livebirths over the 8 years, due to an increase in the rate among infants diagnosed by echocardiography. For every diagnostic-type-by-race group studied, there were increases in the prevalence for those diagnosed by echocardiography and decreases (or no change in one group) for those diagnosed by cardiac catheterization and/or surgery. Although there may have been an increase in actual occurrence of cardiovascular malformation over our study period, it is also possible that wider use of a new echocardiography technology resulted in increased detection.

Black People↗