Gianni Astolfi

Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries

We studied 5,449 cases of cleft lip (CL) with or without cleft palate (CL/P) identified between 1980 and 2000 from the EUROCAT network of 23 registers (nearly 6 million births) in 14 European countries. We investigated specific types of defect sassociated with clefts. Among CL/P cases (prevalence = 9.1 per 10,000), 1,996 (36.6%) affected only the lip (CL) and 3,453 (63.4%) involved CL and palate (CLP). A total of 3,860 CL/P cases (70.8%) occurred as isolated anomalies and 1,589 (29.2%) were associated with other defects such as multiple congenital anomalies of unknown origin (970), chromosomal (455) and recognized syndromes (164). Associated malformations were more frequent in infants who had CLP (34.0%) than in infants with CL only (20.8%). Among multi‐malformed infants, 2 unrelated anomalies were found in 351 cases, 3 in 242 cases, and 4 or more in 377 cases. Among 5,449 CL/P cases, 4,719 were live births (LB) (86.6%), 203 stillbirths (SB) (3.7%), while 508 (9.3%) were terminations of pregnancy (ToP). CL/P occurred significantly more frequently in males (M/F = 1.70), especially among total isolated cases (M/F = 1.87) and CLP isolated cases (M/F = 1.92). The study confirmed that musculoskeletal, cardiovascular, and central nervous system defects are frequently associated with CL/P. An association with reduction anomalies of the brain was found. This association suggests that clinicians should seek to identify structural brain anomalies in these patients with CL/P as the potential functional consequences may be important for rehabilitation and clinical management.

Congenital heart defects: 15 years of experience of the Emilia-Romagna Registry (Italy)

Objectives: Collection and assessment of data from the Emilia-Romagna Region on the occurrence of congenital heart defects in order to identify an homogeneous group of patients for further aetiologic and genetic studies. Materials and methods: The present study is based on 1549 stillborn and live born babies affected by congenital heart defect out of 330,017 consecutive births (4.7 per 1000). Results: The frequency and type of congenital heart defects have been identified together with the sex ratio, associated extracardiac anomalies, chromosomal anomalies and the risk of precurrence in relatives. The impact of prenatal diagnosis on prevalence was low during the study period. Conclusions: The study has provided epidemiological data for public health surveillance of congenital heart defects in the Emilia-Romagna region. The creation of a system for the nationwide recording of congenital heart defects designed with regard to the sources of ascertainment, the diagnostic criteria, and the system of classification is emphasised.

Adverse pregnancy outcomes in a population exposed to the emissions of a municipal waste incinerator

Some contaminants emitted by municipal waste incinerators are believed to adversely affect reproductive health in the exposed populations; yet only limited and conflicting epidemiologic evidence on this issue has been provided so far. In this study we analyzed rates of spontaneous abortion and prevalence at birth of congenital anomalies in women residing or working near the municipal solid waste incinerator of Modena, northern Italy, during the 2003--2006 period and who experienced higher levels of exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans, compared to the remaining municipal population. In women residing in two areas close to the incinerator plant with increasing exposure to dioxins, we did not detect an excess risk of miscarriage (relative risk [RR] 1.00, 95% confidence interval [CI] 0.65-1.48) and of birth defects (RR 0.64, 95% CI 0.20-1.55), nor did any indication of dose-response relation emerge. Among female workers employed in the factories located in the exposed areas, we did not observe a higher risk of spontaneous abortion (RR 1.04, 95% CI 0.38-2.30); however, an increase in prevalence of birth defects was noted (RR 2.26), although this risk estimate was statistically very unstable (95% CI 0.57-6.14). Overall, the study results provide little evidence of an excess risk of adverse pregnancy outcomes in women exposed to emissions from a modern municipal solid waste incinerator.

Risk of congenital anomalies around a municipal solid waste incinerator: a GIS-based case-control study

BackgroundWaste incineration releases into the environment toxic substances having a teratogenic potential, but little epidemiologic evidence is available on this topic. We aimed at examining the relation between exposure to the emissions from a municipal solid waste incinerator and risk of birth defects in a northern Italy community, using Geographical Information System (GIS) data to estimate exposure and a population-based case-control study design. By modelling the incinerator emissions, we defined in the GIS three areas of increasing exposure according to predicted dioxins concentrations. We mapped the 228 births and induced abortions with diagnosis of congenital anomalies observed during the 1998–2006 period, together with a corresponding series of control births matched for year and hospital of birth/abortion as well as maternal age, using maternal address in the first three months of pregnancy to geocode cases and controls.ResultsAmong women residing in the areas with medium and high exposure, prevalence of anomalies in the offspring was substantially comparable to that observed in the control population, nor dose-response relations for any of the major categories of birth defects emerged. Furthermore, odds ratio for congenital anomalies did not decrease during a prolonged shut-down period of the plant.ConclusionOverall, these findings do not lend support to the hypothesis that the environmental contamination occurring around an incineration plant such as that examined in this study may induce major teratogenic effects.

Trihalomethanes, chlorite, chlorate in drinking water and risk of congenital anomalies: A population-based case-control study in Northern Italy

BACKGROUND Epidemiological evidence of an association between disinfection by-products (DBPs) exposure via drinking water and reproductive outcomes is still inconclusive. OBJECTIVE The aim of this study was to investigate the association between trihalomethanes (THMs), chlorite and chlorate exposure and congenital anomalies. METHODS A case-control study was carried out in Emilia-Romagna Region (Italy). Data on 1917 different congenital anomalies (neural tube, cardiac, diaphragm and abdominal wall, oesophagus, cleft lip and palate, respiratory, urinary tract and chromosomal anomalies) observed in the period 2002-2005 were extracted from the Regional Malformation Registry. Four controls (newborns without anomalies) were randomly selected form the Regional Birth Register and frequency matched to cases according to pregnancy period. The network supplying water during the first trimester of pregnancy was identified on the basis of mothers address: DBPs data, technical and structural information were linked to each subject. RESULTS Overall, THMs exposure was very low (mean: 3.8±3.6 μg/l), and no risk excess was observed. Chlorite and chlorate values were fairly high (mean: 427±184 μg/l and 283±79 μg/l, respectively). Women exposed to chlorite level >700 μg/l were at higher risk of newborns with renal defects (OR: 3.30; 95% IC: 1.35-8.09), abdominal wall defects (OR: 6.88; 95% IC: 1.67-28.33) and cleft palate (OR: 4.1; 95% IC: 0.98-16.8); women exposed to chlorate level >200 μg/l were at higher risk of newborns with obstructive urinary defects (OR: 2.88; 95% IC: 1.09-7.63), cleft palate (OR: 9.60; 95% IC:1.04-88.9) and spina bifida (OR: 4.94; 95% IC:1.10-22). CONCLUSIONS This was the first study showing an excess risk of different congenital anomalies related to chlorite and chlorate exposure via drinking water: further research is needed to confirm the observed relationships in large datasets, specifically for chlorate, an unregulated DBP.

766 cases of oral cleft in Italy : data from Emilia Romagna (IMER) and northeast Italy (NEI) registers

Epidemiological and genetic variables for oral clefts were analysed for the years 1981–1989 in a case-control study of congenital malformations in the Emilia Romagna, Veneto, and Friuli regions, and in the Trento and Bolzano hospitals. Birth prevalence for all cases of cleft lip with or without cleft palate (CL(P)) was 8.2 per 10,000 births, and that for cleft palate only (CP) was 6.1 per 10,000. Coexisting abnormalities were found in 23% of CL(P) cases and in 43% of CP. No clusters in time or space were detected. For isolated clefts, a predominance of males among CL(P) and of females among CP was found; epilepsy was the only maternal risk factor correlated with clefts, and an association between clefting and consanguinity was found. Empirical recurrence risks were calculated in both isolated CL(P) and CP.

Does maternal exposure to benzene and PM10 during pregnancy increase the risk of congenital anomalies? A population-based case-control study.

A few studies have suggested an association between maternal exposure to ambient air pollution from vehicular traffic and risk of congenital anomalies in the offspring, but epidemiologic evidence is neither strong nor entirely consistent. In a population-based case-control study in a Northern Italy community encompassing 228 cases of birth defects and 228 referent newborns, we investigated if maternal exposure to PM10 and benzene from vehicular traffic during early pregnancy, as estimated through a dispersion model, was associated with excess teratogenic risk. In conditional logistic regression analysis, and with adjustment for the other pollutant, we found that higher exposure to PM10 but not benzene was associated with increased risk of birth defects overall. Anomaly categories showing the strongest dose-response relation with PM10 exposure were musculoskeletal and chromosomal abnormalities but not cardiovascular defects, with Down syndrome being among the specific abnormalities showing the strongest association, though risk estimates particularly for the less frequent defects were statistically very unstable. Further adjustment in the regression model for potential confounders did not considerably alter the results. All the associations were stronger for average levels of PM10 than for their maximal level. Findings of this study give some support for an excess teratogenic risk following maternal exposure during pregnancy to PM10, but not benzene. Such association appears to be limited to some birth defect categories.

Validation of an algorithm for identifying cases with congenital malformations by using hospital discharge records

OBJECTIVES to evaluate and validate the use of an algorithm designed to identify in hospital discharge records (SDO) cases with congenital malformations (MC) at birth and/or reported in hospitalizations within the first year of life using as gold standard the Congenital malformation Registry of the Local Health Unit of Mantova, Northern Italy, (RMC-MN), which controls all the medical records of infants born to mothers living in the province. DESIGN an algorithm designed for the identification of malformed cases in the SDO database using two modules, one for identification of cases potentially malformed and one for their validation was used. A comparison of the results with those observed by the RMC-MN was then conducted. SETTING AND PARTICIPANTS data of the SDO and the RMC-MN for the period 2010-2011 relative to those detected in newborns within the first year of life in the resident population in the province. RESULTS of 8,042 infants born to mothers residing in the province of Mantova, 7,367 were excluded by the algorithm as malformed with the exception of only one false negative (negative predictive value - NPV: 99.99%); in the remaining 675 cases (8.4%) there was at least one code of congenital malformation. The algorithm has also included 396 cases (4.9%) with isolated minor malformations or diseases considered not malformations, of which 23 were false negatives (NPV: 94.2%). In the remaining 279 cases potentially malformed the algorithm considered as validated 169 cases (60.6%), including 11 false positives (positive predictive value - PPV: 93.5%). In the remaining 110 cases to evaluate, 46 were true positives (PPV: 41.8%). CONCLUSIONS the proposed instrument has identified correctly SDO in 89.4% of cases registered by the RMC-MN to produce a small number of false positives among the validated cases (6.5%) and effectively exclude inappropriate cases (94.2%). The authors suggest a judicious use of the instrument, which should be led by experts of SDO, clinical and epidemiology of congenital malformations.

Emilia-Romagna Study on Pregnancy and Exposure to Antiepileptic drugs (ESPEA): a population-based study on prescription patterns, pregnancy outcomes and fetal health

Objectives To assess the prevalence of antiepileptic drug (AED) exposure in pregnant women and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirths, major birth defects (MBDs), neonatal distress and small for gestational age (SGA) infants following intrauterine AED exposure in the Emilia Romagna region, Italy (4 459 246 inhabitants on 31 December 2011). Methods We identified all deliveries and hospitalised abortions in Emilia Romagna in the period 2009–2011 from the certificate of delivery assistance registry (Certificato di Assistenza al Parto— CedAP) and the hospital discharge card registry, exposure to AEDs from the reimbursed drug prescription registries, MBDs from the regional registry of congenital malformations, and Apgar scores and cases of SGA from the CedAP. Records from different registries were linked. Results We identified 145 243 pregnancies: 111 284 deliveries, 16 408 spontaneous abortions and 17 551 TOPs. Six hundred and eleven pregnancies (0.42%; 95% Cl 0.39 to 0.46) were exposed to AEDs. In the AED-exposed group 21% of pregnancies ended in TOPs vs 12% in the non-exposed women (OR: 2.24; 95% CI 1.41 to 3.56). Rates of spontaneous abortions, stillbirths, neonatal distress and SGA were comparable. Three hundred and fifty-three babies (0.31%; 95% CI 0.28 to 0.35) were exposed to AEDs during the first trimester. MBD rates were 2.3% in the exposed vs 2.0% in the non-exposed pregnancies (OR: 1.12, 95% CI 0.55 to 2.55). Conclusion The Emilia Romagna prevalence of AED exposure in pregnancy was 0.42%, comparable with previous European studies. Rates of spontaneous abortions, stillbirths, neonatal distress, SGA and MBDs following AED exposure were not significantly increased. The rate of TOPs was significantly higher in the AED-exposed women.

Ultrastructural investigations on spermatogenesis and spermatozoan morphology in the endangered Adriatic sturgeon, Acipenser naccarii (Chondrostei, Acipenseriformes): GRANDI et al.

Spermatogenesis was investigated in the Adriatic sturgeon, Acipenser naccarii, by light and electron microscopy. The testis of the unrestricted type had a germinal compartment composed of lobules containing germ cells and Sertoli cells, and separated by a basal lamina from the interstitial compartment, in which Leydig and myoid cells were detected for the first time in Acipenseridae. Spermatogenesis occurred in spermatocysts produced when Sertoli cells became associated with type A spermatogonia of subsequent generations, which produced a clone of synchronized aligned spermatogonia. In primary spermatocytes at zygo‐pachytene stage, the large spherical nucleus contained synaptonemal complexes. The smaller secondary spermatocytes were ovoid with a central round nucleus and scarce cytoplasm. Spermatids were interconnected by cytoplasmic bridges until early spermiogenesis. Chromatin initially condensed as long, twisted, and nonhomogeneous fibers and finally as a compact structure made of thick filaments. Early spermatids showed the flagellum, the primordia of centriole complex and of “implantation fossa,” followed by the acrosomal vesicle formed by Golgi complexes and a fibrous body associated to centriole complex. The spermatozoan head had 10 postero‐lateral projections and a trapezoidal nucleus, a cylindrical midpiece with six to eight mitochondria, the centriole complex, and a “9 + 2” flagellum with a pair of lateral fins. Three helical endonuclear canals crossed the nucleus from the acrosome base to the implantation fossa; their spiralization and that of chromatin fibers suggest a spiral twisting of the nucleus during spermiogenesis. The Sertoli cells performed phagocytosis of degenerating spermatids and spermatozoa. Significant interindividual differences were detected in most morphological parameters of spermatozoa. Data on spermatogenesis in A. naccarii and morphometric measurements on mature spermatozoa provide information about the reproductive biology of the species useful not only for phylogenetic studies but also for evaluation of sperm quality for artificial reproduction projects and restocking of this and other critically endangered sturgeon species.