Sirenomelia is a very rare limb anomaly in which the normally paired lower limbs are replaced by a single midline limb. This study describes the prevalence, associated malformations, and maternal characteristics among cases with sirenomelia. Data originated from 19 birth defect surveillance system members of the International Clearinghouse for Birth Defects Surveillance and Research, and were reported according to a single pre-established protocol. Cases were clinically evaluated locally and reviewed centrally. A total of 249 cases with sirenomelia were identified among 25,290,172 births, for a prevalence of 0.98 per 100,000, with higher prevalence in the Mexican registry. An increase of sirenomelia prevalence with maternal age less than 20 years was statistically significant. The proportion of twinning was 9%, higher than the 1% expected. Sex was ambiguous in 47% of cases, and no different from expectation in the rest. The proportion of cases born alive, premature, and weighting less than 2,500 g were 47%, 71.2%, and 88.2%, respectively. Half of the cases with sirenomelia also presented with genital, large bowel, and urinary defects. About 10-15% of the cases had lower spinal column defects, single or anomalous umbilical artery, upper limb, cardiac, and central nervous system defects. There was a greater than expected association of sirenomelia with other very rare defects such as bladder exstrophy, cyclopia/holoprosencephaly, and acardia-acephalus. The application of the new biological network analysis approach, including molecular results, to these associated very rare diseases is suggested for future studies.

We analyze the allelic polymorphisms in seven Y-specific microsatellite loci and a Y-specific alphoid system with 27 variants (ah I-XXVII), in a total of 89 Y chromosomes carrying the DYS199T allele and belonging to populations representing Amerindian and Na-Dene linguistic groups. Since there are no indications of recurrence for the DYS199CrT transition, it is assumed that all DYS199T haplotypes derive from a single individual in whom the CrT mutation occurred for the first time. We identified both the ancestral founder haplotype, 0A, of the DYS199T lineage and seven derived haplogroups diverging from the ancestral one by one to seven mutational steps. The 0A haplotype (5.7% of Native American chromosomes) had the following constitution: DYS199T, ah II, DYS19/13, DYS389a/10, DYS389b/ 27, DYS390/24, DYS391/10, DYS392/14, and DYS393/13 (microsatellite alleles are indicated as number of repeats). We analyzed the Y-specific microsatellite mutation rate in 1,743 father-son transmissions, and we pooled our data with data in the literature, to obtain an average mutation rate of .0012. We estimated that the 0A haplotype has an average age of 22,770 years (minimum 13,500 years, maximum 58,700 years). Since the DYS199T allele is found with high frequency in Native American chromosomes, we propose that 0A is one of the most prevalent founder paternal lineages of New World aborigines.

The birth prevalence of specific types of congenital anomalies at low and high altitudes in South America were compared after adjustment for prenatal growth, ethnicity, and socioeconomic status. The material includes all 1,668,722 consecutive births occurring in 53 hospitals participating in the Latin-American Collaborative Study of Congenital Malformations (ECLAMC), having registered at least 100 malformed/control pairs between 1967 and 1995. The lowland subsample (below 2,000 m above the sea level) included 46,729 case-control pairs, ascertained in 1,539,432 births from 49 hospitals in 38 cities. The highlands (above 2,000 m) comprised 3,498 case-control pairs from 129,301 births, occurring in four hospitals from three cities. Unconditional logistic regression was used to estimate the relative risks for the exposure at high altitudes, adjusted by ethnicity (Amerindian yes/no), type of health service (public/private), and birth weight (below/equal and greater than 2, 500 g). The adjusted relative risks showed significantly (P < 0.01) higher values in the high than in the lowlands for four types of defects: cleft lip [relative risks (RR): 1.57; 95% confidence interval (CI): 1.27-1.94], microtia (RR: 3.21; 95% CI: 2.35-4.79), preauricular tag (RR: 2.09; 95% CI: 1.86-2.36), branchial arch anomaly complex (RR: 1.79; 95% CI: 1.23-2.61), constriction band complex (RR: 1.92; 95% CI: 1.11-3.31), and anal atresia (RR: 1.61; 95% CI: 1.01-2.57). Conversely, lower risks in the highlands were registered for two neural tube defects: anencephaly (RR: 0.33; 95% CI: 0.20-0.54), spina bifida (RR: 0.57; 95% CI: 0.37-0.78), as well as for hydrocephaly (RR: 0.41; 95% CI: 0.22-0.77) and pes equinovarus (RR: 0.70; 95% CI: 0.51-0.96). Even though some of these differences may be caused by undetected confounders, the coincidental finding of four types of craniofacial defects with higher, and two types of neural tube defect with lower frequencies in the highlands, suggest a real biological foundation.

Several South American countries are fortifying wheat flour with folic acid. However, only Chile started in 2000 to add 2.2 mg/kg, providing 360 microg daily per capita, an acceptable dosage for preventing the occurrence of some neural tube defect (NTD) cases. ECLAMC (Spanish acronym for the Latin American Collaborative Study of Congenital Malformations) routinely monitoring birth defects in South America since 1976, surveyed the impact of this fortification. Data from 361,374 births occurred in 43 South American hospitals, distributed in five different countries, active throughout the 1999-2001 triennium, were selected from the ECLAMC network. Birth prevalence rates for three different congenital anomalies with similar expected prevalence rates, were surveyed by the Cumulative Sum Method (CUSUM) method. They were NTD, oral clefts (OC), and Down syndrome (DS). Expected values were derived from observations made in 1999, and CUSUM was applied to the consecutive series of 24 months covering years 2000 and 2001. Only one of three congenital anomaly types, NTDs, in only one of five sampled out countries, Chile, showed a significant decrease, of 31%, during the 2000-2001 biennium, corresponding to the birth of the periconceptionally fortified infants. The level of significance (P < 0.001) was reached in the 20th month after fortification started, corresponding to August 2001. This is the first observation of a significant decrease in the occurrence of NTD after folic acid food fortification in a population little influenced by confounders common in the developed world as pre-existing secular decreasing trends, and partially unregistered induced abortions.

To verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre-existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congenitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre-fortification periods (1982-1989 and 1990-2000), and from one fortified period (2001-2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre-fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre-fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends.

The impact of prenatal care use on birth outcomes has been understudied in South American countries. This study assessed the effects of various measures of prenatal care use on birth weight (BW) and gestational age outcomes using samples of infants born without and with common birth defects from Brazil, and evaluated the demand for prenatal care. Prenatal visits improved BW in the group without birth defects through increasing both fetal growth rate and gestational age, but prenatal care visits had an insignificant effect on BW in the group with birth defects when adjusting for gestational age. Prenatal care delay had no effects on BW in both infant groups but increased preterm birth risk in the group without birth defects. Inadequate care versus intermediate care also increased LBW risk in the group without birth effects. Quantile regression analyses revealed that prenatal care visits had larger effects at low compared with high BW quantiles. Several other prenatal factors and covariates such as multivitamin use and number of previous live births had significant effects on the studied outcomes. The number of prenatal care visits was significantly affected by several maternal health and fertility indicators. Significant geographic differences in utilization were observed as well. The study suggests that more frequent use of prenatal care can increase BW significantly in Brazil, especially among pregnancies that are uncomplicated with birth defects but that are at high risk for low birth weight. Further research is needed to understand the effects of prenatal care use for pregnancies that are complicated with birth defects.

The aim of the present investigation was to search for a reduction in birth prevalence estimates of 52 selected types of congenital anomalies, associated with folic acid fortification programs in Chile, Argentina, and Brazil. The material included 3,347,559 total births in 77 hospitals of the three countries during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341 (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared pre- and post-fortification rates within each hospital and the resulting Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant reductions in birth prevalence estimates after fortification were observed for neural tube defects (NTDs), septal heart defects, transverse limb deficiencies, and subluxation of the hip. However, only the reduction of NTDs appeared to be associated with folic acid fortification and not due to other factors, because of its consistency among the three countries, as well as with previously published reports, and its strong statistical significance. Among the NTDs, the maximum prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and cephalocele. This observation suggests etiologic and pathogenetic heterogeneity among different levels of spina bifida, as well as among different NTD subtypes. We concluded that food fortification with folic acid prevents NTDs but not other types of congenital anomalies.

Reports of birth defects rates may focus on defects observed in the newborn period or include defects diagnosed at older ages. However, little information is available on the rates of additional anomalies detected after birth or on the ages at which such anomalies are diagnosed. The aims of this work were to describe the initial diagnoses of oral clefts, isolated or associated with other defects, in newborn infants ascertained in hospitals of the ECLAMC network, and diagnostic changes that occurred due to detection of additional defects during a one-year follow-up period. Seven hundred ten liveborn infants with cleft lip only (CLO), cleft lip with cleft palate (CLP), or cleft palate (CP) were ascertained between 2003 and 2005. Prevalence estimates of isolated and associated clefts, diagnoses in infants with associated clefts, and the percentage of isolated clefts that were reclassified as associated were established. Birth prevalence estimates (per 1,000) were as follows: Total: 1.7; CLP: 0.94 (ASO=23.5%); CP: 0.46 (ASO=42.3%); CLO: 0.28 (ASO=7.6%). Initial diagnoses in infants with associated clefts included 38 infants with chromosomal abnormalities, 33 with non-chromosomal syndromes, 16 with malformation sequences, and 98 with multiple anomalies of unknown etiology. Seven percent of newborns initially classified as isolated were later reclassified as associated. Ten infants without associated defects or clinically suspected syndromes were diagnosed as syndromic only through laboratory findings or family history, illustrating the difference between the terms associated vs. isolated, which refers to presence or absence of associated anomalies, and syndromic vs. non-syndromic, which refers to etiology.