Altitude as a risk factor for congenital anomalies

Abstract

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.

Prevalence at birth of congenital abnormalities of external ears in Hungary

“…Among methodological differences, the classification-whether only isolated or isolated and unclassified multiple or isolated, unclassified multiple and specified CA syndromes of microtia/anotia are evaluated-and ascertainment-whether type I/minor microtia or Facio-Auriculo-Vertebral Spectrum: FAVS is included to the group of isolated microtia/anotiaproblems need to be mentioned, beyond the differences in the completeness of ascertainment and the quality of diagnoses. However, population characteristics are also important: microtia/anotia is relatively rare in white and black people, more frequent in Hispanics, mainly in children born in Mexico [15] and particularly in regions within special geographical clusters of microtia/anitia as in Quito, Ecuador [14] and the Navajo Indians in the USA state of New Mexico [16], in addition to populations living in high altitudes [17]. Nevertheless, differences in ascertainment and diagnostic criteria are probably the major source of great variations in the rate of external ear CAs, mainly microtia/anotia; therefore, their comparison demands caution among interpreting data for different populations/registries/studies.…”

Orofacial Clefts: A Worldwide Review of the Problem

“…Oral clefts frequently occur in combination with a wide range of chromosomal abnormalities and syndromes (trisomy 13, amniotic band anomalad, Fryns syndrome, Meckel syndrome, Stickler syndrome, Treacher Collins syndrome, van der Woude syndrome, Velocardiofacial syndrome, etc.) [24] and environmental factors such as medication during pregnancy, maternal alcohol consumption and smoking, dietary and vitamin deficiencies, diabetes, environmental toxins, altitude, birth order, socioeconomic status, and parental age [25][26][27][28][29]. Other genetic factors that may affect the presence of OFCs include maternal ability to maintain red blood cell zinc concentrations and myoinositol concentrations (a hexahydroxycyclohexane sugar alcohol) [30].…”

Methylenetetrahydrofolate Reductase (MTHFR) Allele Frequencies in Amerindians

“…Residents with Amerindian background born in three high-altitude Andean cities (between 2600 m and 3600 m) and in 38 low-altitude cities (between 5 m and 905 m) were surveyed for a number of conditions, and relatively low frequencies of anencephaly [relative risk (RR 0.33)], spina bifida (RR 0.57), hydrocephaly (RR 0.41) and pes equinovarus (RR 0.70) were found in the high altitude samples (Castilla et al 1999). Although the data were not stratified according to ethnic origin, the high frequency of aboriginal people in the high-altitude sample suggests that the difference in susceptibility to neural tube defects (NTDs) may be characteristic of these populations.…”