[Comparison of the cardiovascular predictive value of MDRD and CKD-EPI in estimating chronic kidney disease]. / Comparación del valor predictivo cardiovascular de MDRD y CKD-EPI en la estimación de la enfermedad renal crónica.

OBJECTIVE: To assess predictive value of the cardiovascular prognosis by comparing the two most used formulas for the estimation of glomerular filtration rate in hypertensive patients. MATERIAL AND METHODS: A retrospective cohort study was designed that included 405 patients diagnosed with essential hypertension. The patients were referred from Primary Care to the Hypertension and Vascular Risk Unit between January 1, 1998 and August 31, 1999. Blood pressure measurements, blood and urine analysis, and echocardiography were simultaneously performed. They were followed up for 12.5 years (mean [± IQR]: 10.61 [± 3.11] years) and 174 events were recorded. RESULTS: The study included 405 patients (53.8% women), with a mean age of 55.5 years. The estimated glomerular filtration rate according to the MDRD and CKD-EPI equations was 73.9±2.6 mL/min/1.73m(2) and 76.9±2.2 mL/min/1.73m(2), respectively. The prevalence of chronic kidney disease was 31.6% and 23.9%, respectively. Using the CKD-EPI equation led to the re-classification of 22.9% of patients. The incidence rate ratio (IRR [95%CI] for chronic kidney disease identified by the MDRD equation was 2.4 [1.8-3.3], and for the CKD-EPI calculation it was 2.5 [1.8 to 3.3]). CONCLUSIONS: Both equations estimate similar magnitudes of renal function, although the CKD-EPI equation has less false positives, and both have similar prognostic values in patients at high cardiovascular risk as well those at low risk.

[Carotid intima-media thickness distribution according to the stratification of cardiovascular risk by means of Framingham-REGICOR and score function charts]. / Distribución del grosor íntima-media carotídeo en función de la estratificación del riesgo cardiovascular según las funciones de Framingham-REGICOR y SCORE.

BACKGROUND: Carotid intima-media thickness (cIMT) has been suggested as a further tool for risk function charts. The aim of this study was to describethe relationship between cIMT and cardiovascular risk (CVR) estimation according to Framingham-REGICOR and SCORE equations. METHODS: Observational, cross-sectional cohort study from 362 hypertensive subjects. Demographic and clinical information were collected as well as laboratory, ultrasonographic and CVR estimation by the Framingham-REGICOR and SCORE functions. Statistical analysis was performed using SPSS software (version 20,0). To analyze the data, statistical tests such as Chi-square, T-test, ANOVA, and Pearson correlation coefficient were used. RESULTS: According to both functions, differences on mean cIMT were found between low CVR group and intermediate to high groups. No differences were found between intermediate and high risk groups (cIMT: 0,73mm low risk patients vs. 0,89 or 0,88mm respectively according to SCORE function and cIMT: 0,73 vs. 0,85 or 0,87mm respectively according to Framingham-REGICOR function). cIMT correlated positively with CVR estimation according to both SCORE (r=0,421; P<.01), and Framingham-REGICOR functions (r=0,363; P<.01). CONCLUSIONS: cIMT correlates positively with CVR estimated by SCORE and Framingham-REGICOR functions. cIMT in those subjects at intermediate risk is similar to those at high risk. Our findings highlight the importance of carotid ultrasound in identifying silent target-organ damage in those patients at intermediate CVR.

VATERL: an epidemiologic analysis of risk factors.

This work analyzed the incidence of risk factors in 138 cases presenting two or more of five components defining VATERL, with no other recognized unrelated anomalies: vertebral anomalies, anal atresia, esophageal atresia with or without tracheoesophageal fistula, renal anomalies, and preaxial defects of the upper limbs, including polydactyly of the thumb. The 138 infants were ascertained among 1,811,461 births examined in the 1967-1994 period by the Latin-American Collaborative Study of Congenital Malformations: ECLAMC. One healthy and one malformed control newborn infant were matched to each VATERL case. The birth prevalence rates (per 100,000 births) for VATERL were significantly lower in Venezuela (3.1) than in the other eight countries (8.8) (P < 0.001). Venezuela also had lower rates for all five VATERL defects, even after excluding the 138 VATERL cases. VATERL cases were preferentially males (male proportion 0.6261) (P < 0.02), and, when compared with healthy controls, they had a higher perinatal mortality rate (63.7%) (P < 0.005), a higher frequency of fetal losses in previous pregnancies (12.6%) (P < 0.05), and lower mean birthweights (2,361.79 +/- 809.63 g) (P < 0.005). VATERL cases showed a higher rate than matched malformed controls for prenatal exposures to drugs and physical agents (P < 0.02 and P < 0.05, respectively), although no specific pharmacological or physical group was involved. The lower birth prevalence rates found in Venezuela, for VATERL as well as for each of the five congenital anomalies involved in this association, seem to be biologically meaningful. Since we could not identify a potential risk factor, nor a common cause of underascertainment unique to the Venezuelan subsample and common to all six hospitals, no hypothesis can be advanced here for this phenomenon. Nevertheless, this unequal geographic distribution strongly suggests a common etiopathogenicity for the five congenital anomalies involved in the VATERL association.

VACTERL association, epidemiologic definition and delineation.

This study departed from a preconceived definition of VACTERL, including more than one of these six anomalies in the same infant: V (vertebral anomalies), A (anal atresia), C (congenital heart disease), TE (tracheoesophageal fistula or esophageal atresia), R (reno-urinary anomalies), and L (radial limb defect). Under this definition, 524 infants were ascertained by ECLAMC from almost 3,000,000 births examined from 1967 through 1990. Observed association rates among VACTERL components as well as between VACTERL and other defects were compared against randomly expected values obtained from 10,084 multiply malformed infants (casuistic method) from the same birth sample. Conclusions were: 1) Cardiac defects are not a part of VACTERL. 2) Single umbilical artery, ambiguous genitalia, abdominal wall defects, diaphragmatic hernia, and anomalies that are secondary to VACTERL components (intestinal and respiratory anomalies, and oligohydramnios sequence defects) are frequent enough to be considered an "extension" of VACTERL, and cardiac defects should be included in this category. 3) Neural tube defects are negatively associated with VACTERL which could not be explained by selection bias or any other operational artifact. High embryonic lethality or mutually exclusive pathogenetic mechanisms could be suitable explanations. 4) Results were not clear enough to determine whether VACTERL should be defined by at least two or three component defects.

Pectoralis major muscle defect and Poland complex.

Pectoralis major muscle defect (PMD) was diagnosed in 27 infants from a series of 599,109 live births in South America (1/22,189). In all 27 cases the PMD was unilateral, mainly affecting the right side (20/27), and there were more male (19/27) than female cases. No familial cases and no parental consanguinity were recorded. A positive correlation was observed between PMD and sex hormone intake and vaginal bleeding in the first trimester of pregnancy. In 12 (1/49,925) of the 27 PMD cases hypoplasia and/or syndactyly of the ipsilateral hand was also diagnosed. The index-middle interdigital space was affected in all 11 cases with symbrachydactyly. Additional congenital anomalies were observed in 4/27 cases, and they were: hemangiomas, hypospadias, and clubfeet. Poland complex (12 cases), isolated PMD (15 cases), and isolated symbrachydactyly (18 cases), showed a similar pattern for symmetry, sidedness, syndactyly type, and sex ratio.

Hypospadias: an epidemiological study in Latin America.

Epidemiological variables in relation to hypospadias were analyzed in a case-control study of a liveborn population from six Latin American countries. the frequency of hypospadias was 7.6 per 10,000 livebirths (324/423,839). The cases were divided into three types: distal (72%), proximal (18.5%) and non-specified cases (9.5%). The control group consisted of the first nonmalformed child born after each of the patients and was matched by sex, place, and time of birth. Other coexisting malformations were found in 13.6% of cases. The Brazilian sample showed the highest incidence rate (17.7/10,00) and also the highest incidence of severe forms (5.0/10,000) as compared with the other countries. a circannual rhythm was detected using several different statistical procedures. Low mean birth weight, twinning, vaginal bleeding, and drug exposure during the 1st trimester (particularly sex hormones) were found to be risk factors. The more severe forms had a higher neonatal mortality rate and higher inbreeding when compared with the controls or milder forms. The heritability coefficient was 0.6772 +/- 0.0675. The possible role of maternal sex hormone intake and disturbances of human chorionic gonadotropin during the first trimester are discussed.

Syndactyly: frequency of specific types.

Syndactyly without other combined limb anomalies, Poland complex, or amniotic bands, was diagnosed in 174 of 599, 109 consecutive newborn infants (3/10,000). Syndactyly was the only diagnosed anomaly in 133 cases, and it was associated with other anomalies in 41. The most common type of syndactyly was isolated syndactyly of the second and third toes (70 cases), which affected more males than females, and had a higher than expected frequency of white non-Latin-European ancestry. The second most frequent type was isolated syndactyly of the middle and ring fingers (18 cases), and the third was isolated syndactyly of the fourth and fifth toes (13 cases). Considering both isolated and syndromal cases, 66% (114/172) could be assigned to one or another of the fourth genetic categories of syndactyly described by Temtamy and McKusick [1978]. This, plus the high frequency of affected first degree relatives observed (25/434:6%), suggests that the genetic forms of syndactyly may be more common than might be suspected from the small number of pedigrees in the literature.

Hand and foot postaxial polydactyly: two different traits.

The aim of this work was to test whether postaxial hexadactyly had different clinical and epidemiological characteristics depending on hand or foot involvement. In the period 1967-1993, the Latin-American Collaborative Study of Congenital Malformations (ECLAMC) enrolled 1,582,289 births, and 2,271 cases with isolated (nonsyndromal) postaxial polydactyly (5th-digit hexadactyly). The prevalence was 14.3/10,000 births. Postaxial polydactyly (PP) of the hand (HPP) was the most frequent type (N:1,733; 76.3%; prevalence: 11.0/10,000), followed by foot PP (FPP=N:351; 15.5%; prevalence: 2.2), and hand and foot PP (BPP=N:187; 8.2%; prevalence: 1.2). Unlike HPP (55.0% bilateral; 77.2% left), FPP was less frequently bilateral (19.4%), with lower preference for the left side (55.5%). As expected, HPP was associated with African Black ethnicity, male sex, twinning, low maternal education, parental consanguinity, and there was frequent recurrence in 1st-degree relatives. Conversely, FPP was associated with Amerindian racial background, parental subfertility, and bleeding in the 1st trimester of pregnancy. BPP displayed the highest frequency of associated congenital defects (23.4%, vs HPP:6.6%, FPP: 15.4%). In its isolated form, BPP resembled HPP more than FPP with respect to left preference (90.9%), familial recurrence (11.0% of 1st degree relatives), and low maternal education. Although male sex preference and high frequency of twinning was observed in the 3 PP subtypes, statistical significance was present only in HPP. None of the 3 PP subtypes showed abnormal values for perinatal mortality, birth weight, length of gestation, parental ages, or parity. A logistic regression analysis showed Black race only to be associated with HPP, parental subfertility with FPP, parental consanguinity with BPP, and non-Black race with both FPP and BPP. The data presented here are the first indication that HPP and FPP are 2 different entities, with a larger genetic component in HPP than in FPP.

Survival of children with Down syndrome in South America. ECLAMC-Downsurv Group. Latin American Collaborative Study of Congenital Malformations.

The first step of all healthcare actions aimed at promoting an appropriate quality of life for infants affected by Down syndrome (DS) is to ensure their survival. This investigation was aimed at estimating the infant mortality rate of infants affected with DS in urban populations of South America. Thirty-three hospitals included in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) distributed in 23 cities of 5 South American countries followed 360 liveborn DS cases born during the 1988-1992 period. Families were recontacted after the infant should have reached the age of one year. The collected data included information about health status; i.e., frequency and dates of diagnosed illnesses and hospital admissions, and, in case of death, information on date, place and cause of death, and illness immediately before death. Information about the interviews included place, date, and name of the interviewer. A closed questionnaire was employed by the interviewers, mostly physicians, nurses, and social workers. Life table analysis up to the age of one year was performed by the actuarial survival method. The overall mean survival at age one year was 0.736 (SE=0.023). Thirty-three (9.2%) of the 360 cases died neonatally, and 62 (17.2%) within the remaining 2-to-12-month interval. The probability of survival at one year of age did not differ between public (209 cases; mean 0.718; SE=0.031) and private (151 cases; mean: 0.762; SE=0.035) (chi2:0.87; df:1; P >0.05) health systems. The 150 DS cases with a congenital heart defect (CHD) had a significantly lower P robability of survival at the age of one year (mean: 0.660; SE: 0.039) than did the 210 cases without CHD (mean: 0.790; SE: 0.028) (chi2:6.67; df:1; P <0.01). The death rate in the first year of life for DS cases without a detected cardiac defect (21%) is significantly higher than that reported in developed countries; namely, 16% from Italy, 11% from Canada, 10% from England, and 7% from Denmark.

Umbilical cord insertion: normal location in neonates.

The distances between the xyphoid appendix and the insertion point of the umbilical cord (XU) and between the xyphoid appendix and upper edge of the pubic symphysis (XP) were measured in 201 newborn infants. The mean ratio XU/XP was 0.62 (S.D. 0.044) with no differences between sexes nor correlations with weight or length. Ratios lying between 0.53 and 0.71 can be considered as within the normal range.

Birth defects monitoring in underdeveloped countries: an example from Uruguay.

Medical authorities in developing countries are primarily interested in nutritional and infectious diseases. Therefore, activities directed to the prevention and control of low priority illnesses, such as birth defects, need to be particularly effective, simple, and economical. Monitoring of congenital anomalies is one of the preventive activities which can be efficiently performed at very low cost. Guidelines for this are given, and their application exemplified by the case of Uruguay. Uruguay has recently attained an infant mortality rate of 20/1,000, with the congenital anomalies ranking as its second cause. The government of Uruguay, through the Pan American Health Organisation/World Health Organisation (PARO/WHO) called the Estudio Colaborativo Latino Americano de Malformaciones Congenitas (ECLAMC) for advice in order to plan a program for the prevention of birth defects. The recommendations given were based on conclusions drawn from the analysis of data the ECLAMC program has been accumulating, from Uruguay and other Latin-American countries, since 1967. The case of Uruguay clearly indicates that sensible guidelines for birth defects prevention can be provided, after working with this "low priority and uninteresting" group of illnesses for more than twenty years.

Descriptive system for congenital limb anomalies.

A descriptive system for the nomenclature, notation and classification of congenital limb malformations, suitable for clinical, epidemiological and experimental use is presented. Every developmental limb anomaly is described by stating the type of anomaly and the affected anatomic structure. All anomalies are classified into three basic types: excess, deficiency and fusion. The anatomic structure of the affected limb is defined within a two dimensional order. This system was used to describe 652 cases with isolated developmental limb anomalies obtained from two series of observations. The observed data are presented in a progressively expanded classification ranging from 4 to 497 diagnostic categories. Observed incidence rates for the four main types of anomaly from a sample of 297,299 consecutive livebirths, are: excess: 1.22; deficiency: 0.17; fusion: 0.20; combined: 0.24 per thousand.

Sternum length and intermammillary distance in normal newborns.

Short sternum and widely spaced nipples are recognized clinical findings in Edwards' and Patau's syndromes and in Noonan's, Turner's and renal hypoplasia syndromes, respectively. Sternum length, intermammillary distance, length of trunk and thoracic circumference were measured in 307 consecutive live newborns. Intermammillary distance was found to have the highest partial regression coefficient over sternum length. It seems therefore advisable to consider both parameters in the phenotypic description of syndromes where an abnormal variation of one of them is suspected.

Patterns of combined limb malformations.

Seven different limb malformations types were defined in 544 affected newborns, apparently free from other anomalies, obtained from a series of 297,299 livebirths. These seven malformation types were: polydactyly, limb reduction, brachydactyly, symphalangy, syndactyly and split hand/foot. One anomaly type was present in 472 newborns (1.58/1,000) and two or three in 72 (0.24/1,000). The observed combinations of two or three limb malformation types cannot be explained as chance association. Therefore, a common etiopathogenic mechanism has to be considered when two or more limb malformation types are combined in a given individual. The most frequent observed combinations were: reduction-brachydactyly, reduction-syndactyly, brachydactyly-syndactyly, polydactyly-syndactyly, and reduction-brachydactyly-syndactyly. Based on affected limb distribution, sex ratio, and familial recurrence rates, it is suggest that a reduction anomaly is the primary component in all tested combinations while syndactyly tends to be a secondary one when combined with any other limb anomaly type.

Previous miscarriage and stillbirth as risk factors for other unfavourable outcomes in the next pregnancy.

OBJECTIVE: To look for associations between previous fetal loss and fetal malformation or low birthweight in a subsequent pregnancy. DESIGN: A case-control study with place of birth, time and sex matched controls. SETTING: 72 South American maternity hospitals. SUBJECTS: 18,534 malformed, 1150 non-malformed babies of low birthweight and 16,394 controls. All babies were from mothers with at least one previous pregnancy. MAIN OUTCOME MEASURES: Frequency of stillbirths and miscarriages in the previous pregnancy and outcome of the index pregnancy. RESULTS: Multiple malformation, Down's syndrome, anencephaly, spina bifida, pes equinovarus, congenital dislocation of the hip and low birthweight are associated with previous fetal loss. CONCLUSION: A miscarriage or a stillbirth in a previous pregnancy should be taken into account when the risk of malformations or low birthweight in a subsequent pregnancy is assessed.