Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Prenatal genetic counseling referrals for advanced maternal age: still room for improvement.

OBJECTIVE: The objective of this study is to evaluate genetic risks already present before pregnancy in a cohort of pregnant women referred for prenatal genetic counseling exclusively for advanced maternal age (AMA). METHOD: We retrospectively reviewed the records of 1353 women referred over 1 year (2010) for pre-test genetic counseling with the only indication of AMA at three Italian Clinical Genetic Services. RESULTS: Of the 1353 women fulfilling the inclusion criteria of the study, 87 (6.4%) had cumulatively 94 genetic risk factors not previously identified (one risk factor in 80 patients and two risk factors in seven). Twenty-six risk factors (27.7%) concerned heterogeneous or multifactorial conditions and 68 (72.3%) Mendelian or chromosomal disorders and consanguinity.In nine out of these 87 women, the estimated risk for the offspring of a genetic disease or a significant structural anomaly was >5%. Additional testing according to the identified risks was performed in 36 of these 87 women/families. CONCLUSIONS: The proportion of cases with additional risk factors is smaller than reported in previous studies, but it remains substantial and confirms the need for strategies to increase awareness of the public and health professionals responsible for the care of women in childbearing age.

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.

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.

Regional differences in the motor response to capsaicin in the guinea-pig urinary bladder: relative role of pre- and postjunctional factors related to neuropeptide-containing sensory nerves.

Capsaicin induced a contraction of isolated strips from the guinea-pig urinary bladder which was more evident in the dome than in the neck and inhibited contractions induced by field stimulation, particularly in the neck. Both responses exhibited prompt desensitization and were tetrodotoxin-resistant, suggesting a specific action on transmitter release from sensory nerve terminals. Indeed, the contractile response in the dome was prevented by a substance P antagonist while the inhibitory response in the neck was prevented by immunoblockade with anticalcitonin gene-related peptide (CGRP) serum. Substance P produced a contraction of the guinea-pig bladder, being about 5 times more potent in the dome than in the neck, while CGRP inhibited the evoked contractions, being about 8 times more potent in the neck than in the dome. Further, the maximal effect of CGRP in the neck was almost double that in the dome. Substance P- and CGRP-like immunoreactivity were detected in both the dome and the neck with no regional differences for each peptide. CGRP-like immunoreactivity was 6.3 and 7.9 times higher than substance P-like immunoreactivity in the dome and the neck, respectively. Exposure to capsaicin evoked release of both substance P- and CGRP-like immunoreactivity from the dome and the neck. Peak CGRP-like immunoreactivity released by capsaicin was 12.3 and 8 times greater than substance P-like immunoreactivity in the dome and the neck, respectively. For each peptide, no difference was found in peak release in the dome vs neck. Total substance P-like immunoreactivity released from the neck was 25% lower than that released from the dome. The ability of CGRP to stimulate accumulation of 3',5' cyclic adenosine monophosphate in membranes prepared from the bladder muscle was greater in preparations from the neck than from the dome. These findings indicate that postjunctional mechanisms (type and number of receptors for sensory neuropeptides, coupling with second messengers) are a major determinant of the type of motor responses consequent of the release of sensory neuropeptides from capsaicin-sensitive nerves.

[Standardization and stability of reagents for the titration of anti-tetanus antibodies by means of the passive hemagglutination technic]. / Standardizzazione e stabilità di reagenti per la titolazione di anticorpi antitetanici mediante la tecnica di emoagglutinazione passiva.

The evaluation of the antitetanus immunity in human sera is of primary importance for the carrying out of an adequate prophylaxis and treatment of tetanus. Tetan Test is a diagnostic kit for the titration of the antitetanus antibodies, by means of the passive hemagglutination technique. Tetan Test is examined under the point of view of the preparation techniques and the process and final controls which warrant the quality and the standardization of the product itself. The stability of Tetan Test, after storage at the temperatures: 67 degrees C, 52 degrees C, 37 degrees C, 22 degrees C is evaluated. The excellent results obtained allow the use of the product also in hot climates, in developing countries, where the storage at the advised temperatures is not possible.

[Influence of age on blood glucose levels: percentile reference intervals determined on ambulatory patients]. / Influenza dell'età' sui livelli glicemici: intervalli di riferimento percentili determinati su pazienti ambulatoriali.

Data of routine chemical and hematological laboratory tests regarding outpatients were collected in four different hospitals of the provinces of Ferrara, Rovigo and Bologna. Data of about 1500 subjects per hospital were cumulated without preliminary selection of patients; sex, age and pregnancy status were also recorded. At the end of the collection, the second (and third) record of the same patient was discarded; only those referring to the first examination were retained. In this report we consider only the values of the blood sugar level which were obtained by enzymatic methods. Descriptive statistics and regression analysis were performed utilizing a CDC CYBER 70/76 computer. The means and the variances of the data collected at the four hospital laboratories were very similar (Tab 1). The interlaboratory analysis of variance was poorly significant. All frequency distributions were leptocurtic and skewed to the right (Fig. 1). The blood sugar level tend to increase with age (Tab. 2). This correlation is graphically depicted in a two-dimensional plot (Fig 2) in which the regression line and the 2, 5 and 97,5 percentile levels corrected for age were also reported. We think that this diagram may be more helpful to the clinicians interpreting laboratory results than the usual "normal values".

Complement fixation reaction in toxoplasmosis.

In toxoplasmosis serodiagnosis the complement fixation reaction (CF) is barely sensitive and specific and supplies results below the general standard levels of this technique. The reasons for this deficiency are discussed and detected in the preparation modalities of the toxoplasma antigens. Two diagnostic antigens are prepared and evaluated; the former, a suspension of whole toxoplasma (WT) the latter a total extract of toxoplasma (TET). The antigens are characterized by the preparative process, culture host and the extractive technique with a modified ultrasonic disintegrator. The antigens are used in the CF reaction, performed with the modified LBCF method, with a 100% hemolysis reading (H 100). The LBCF-H 100 reaction with WT and TET antigens is evaluated parellely to the indirect immunofluorescence reaction (IF) and dye test (DT) on 2514 human sera from cases os suspected toxoplasmosis and pregnant women. The analysis of the serological results pointed out that the LBCF-H 100 reaction performed with WT antigen, shows a sensitivity and specificity equivalent to that of the DT. The LBCF-H 100 reaction with TET antigen extends the range of the antibodies detectable with WT antigen. The optimal serological combination to identify the highest number of seropositive cases of toxplasma infection is given by LBCF-TET and IF reactions.