Amelia: a multi-center descriptive epidemiologic study in a large dataset from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature

Abstract

This study describes the epidemiology of congenital amelia (absence of limb/s), using the largest series of cases known to date. Data were gathered by 20 surveillance programs on congenital anomalies, all International Clearinghouse for Birth Defects Surveillance and Research members, from all continents but Africa, from 1968 to 2006, depending on the program. Reported clinical information on cases was thoroughly reviewed to identify those strictly meeting the definition of amelia. Those with amniotic bands or limb-body wall complex were excluded. The primary epidemiological analyses focused on isolated cases and those with multiple congenital anomalies (MCA). A total of 326 amelia cases were ascertained among 23,110,591 live births, stillbirths and (for some programs) elective terminations of pregnancy for fetal anomalies. The overall total prevalence was 1.41 per 100,000 (95% confidence interval: 1.26-1.57). Only China Beijing and Mexico RYVEMCE had total prevalences, which were significantly higher than this overall total prevalence. Some under-registration could influence the total prevalence in some programs. Liveborn cases represented 54.6% of total. Among monomelic cases (representing 65.2% of nonsyndromic amelia cases), both sides were equally involved, and the upper limbs (53.9%) were slightly more frequently affected. One of the most interesting findings was a higher prevalence of amelia among offspring of mothers younger than 20 years. Sixty-nine percent of the cases had MCA or syndromes. The most frequent defects associated with amelia were other types of musculoskeletal defects, intestinal, some renal and genital defects, oral clefts, defects of cardiac septa, and anencephaly.

Figure 1

Clinical photographs of some amelia cases, showing total absence of a limb; (a) amelia of the upper left limb; (b) amelia of the right lower limb; (c) amelia of the right upper limb combined with anencephaly; (d-1, d-2, and d-3) amelia of a lower limb combined with phocomelia of the contralateral lower limb (Courtesy of Dr. A. Sanchis, Dr. S. Martínez, Dr. I. Arroyo Carrera, and Dr. E. Burón).

Figure 2

Total prevalence of amelia per 100,000 births (bar) and 95% confidence interval (bracketed line) by surveillance program, and overall total prevalence (dotted line), in 20 surveillance programs of the International Clearinghouse for Birth Defects Surveillance and Research.

Figure 3

Prevalence ratios for maternal age groups relative to the reference age of <20 years with corresponding 95% CIs for amelia in 18 surveillance programs^★ of the International Clearinghouse for Birth Defects Surveillance and Research (syndromic cases excluded). ^★Cases and births excluded for the following programs because no births by maternal age were available: China Beijing <1997 and >2003, Germany Saxony–Anhalt <1991, Italy Emilia Romagna <1985, Italy North East, Italy Sicily.