Epidemiological Characteristics of Amniotic BandSequence (ABS) and Body Wall Complex (BWC):Are They Two Different Entities?

M.L. Martınez-Frıas*ECEMC and Departamento de Farmacologıa, Facultad de Medicina, Universidad Complutense, Madrid, Spain

In 1965, Torpin [1965; Am J Obstet Gynecol91:65–75] concluded that fetal constrictionsand amputations were related to amnioticmembrane rupture. Since then, this viewwas accepted widely, although differentterms were used due to the variation in thetypes of associated anomalies. I considerthat for those cases without body wall de-fects, the most appropriate term is amnioticband sequence (ABS), since amnion rupturecould initiate a cascade of abnormalities(consequences) leading to the final struc-tural defects.

Here I present a clinical and epidemio-logical analysis of a series of consecutive in-fants with ABS, comparing their character-istics with those of infants with body wallcomplex (BWC). The results of this analysissuggest that ABS, from an epidemiologicalstandpoint, is an entity different from BWC,and that amniotic bands in cases of BWCmay be considered different from amnioticbands in cases without body wall defects.The former are probably produced earlierin the development than the latter. Am. J.Med. Genet. 73:176–179, 1997.© 1997 Wiley-Liss, Inc.

KEY WORDS: amniotic bands; body walldefects; ABS; BWC; epidemi-ology

INTRODUCTIONIn 1965, Torpin concluded that fetal constrictions

and amputations were related to amniotic membrane

rupture. Since then, this pathogenetic hypothesis wasaccepted widely. However, due to the variation in thespectrum of associated malformations, disruptions,and deformations observed in the affected infants, di-verse terms were used. It has been called amnioticband syndrome [Chemke et al., 1973; Kino, 1975; Os-sipoff and Hall, 1977; Seeds et al., 1982; Fiedler andPhelan, 1983], ADAM complex [Herrmann and Opitz,1974; Keller et al., 1978], amniotic band disruptioncomplex [Higginbottom et al., 1979], body wall defectswith limb deformities [Pagon et al., 1979], limb bodywall complex [Van Allen et al., 1987a,b], and the am-niotic band sequence (ABS) [Hunter and Carpenter,1986; Kalousek and Bamforth, 1988]. I consider ABSthe most appropriate term for those cases without bodywall defects, since amnion rupture could initiate a cas-cade of abnormalities (consequences) leading to the fi-nal structural defects.

Here I present a clinical and epidemiological analy-sis of a series of consecutive infants with ABS (withoutbody wall defects), comparing their characteristics withthose of infants with body wall complex (BWC) of anyetiology. The aim of this analysis is to identify if, froman epidemiological standpoint, it can be determinedthat ABS is an entity different from BWC.

MATERIALS AND METHODSThe data is derived from the Spanish Collaborative

Study of Congenital Malformations (ECEMC), a hospi-tal-based case-control study and surveillance system.The ECEMC methodology has been published repeat-edly [Martınez-Frıas, 1994, 1995; Martınez-Frıas andUrioste, 1994].

I have considered as cases with ABS those infantswithout body wall defects but with either limb or digi-tal band constrictions or amputations, or craniofacialdisruptive defects, with or without other congenitalanomalies. As BWC, we have considered all those in-fants with body wall defects (of any cause, includingamniotic bands) associated or not with any other de-fect, excluding the infants with isolated gastroschisis[Martınez-Frıas, 1997]. Omphalocele was not consid-ered a body wall defect.

Between April 1976 and March 1996 the ECEMCsurveyed 1,309,850 liveborn infants. Among them24,366 had major and/or minor anomalies detected at

Contract grant sponsor: Direccion General de Salud Publica delMinisterio de Sanidad y Consumo of Spain; Contract grant spon-sor: Fundacion 1000 para la investigacion sobre defectos congeni-tos of Spain.

*Correspondence to: Dr. M.L. Martınez-Frıas, ECEMC, Fac-ultad de Medicina, Universidad Complutense, 28040, Madrid,Spain.

Received 7 March 1997; Accepted 22 May 1997

American Journal of Medical Genetics 73:176–179 (1997)

© 1997 Wiley-Liss, Inc.

birth, and 62 had ABS. Between January 1980 andMarch 1996, a total of 8,572 stillborn infants was ana-lyzed and 492 of them had congenital anomalies.Among these, 6 had ABS (Table I). The cases with BWCwere those 31 included in our previous paper [Mar-tınez-Frıas, 1997].

RESULTS

Table I shows the global and annual prevalence oflive and stillborn infants with ABS, as well as in thetotal births. The differences between the prevalencefigures by years among liveborn infants and among thetotal births are statistically significant. Among the to-tal births, there is a statistically significant decreasinglinear trend. The analysis of the homogeneity and thelinear trend of the prevalence figures by year amongstillborn infants are not statistically significant. Ex-cept for the high prevalence observed in 1980, the otherdifferences may be influenced by prenatal diagnosisand voluntary interruption of gestation (VIG), at leastfor the more recent years (after 1985, when VIG be-came legal in Spain) and the most severe forms.

Table II analyzes the sex ratio of infants with ABSwith and without other congenital anomalies, as wellas for those cases with BWC. Isolated ABS are morefrequently observed in females, while the other 2groups are more frequently males.

Tables III and IV analyze the epidemiological char-acteristics of children in each study group. Birthweight (Table III) is lower in cases with BWC than inthose groups with ABS, for a similar gestational age.However, while the placental weight is similar in the 3study groups, the length of the umbilical cord is muchsmaller in infants with BWC than in those with ABS.Other characteristics (Table IV) such as breech presen-tation, in the sample, is more frequent in infants withBWC than in those with ABS although the differencedoes not reach the level of significance, probably due tothe sample size. On the contrary, the differences be-tween ABS and BWC are not so disparate for the exis-tence of previous abortions in the mothers’ pregnanciesand for the existence of vaginal bleeding.

Table V shows that, in the sample, the means of ma-ternal and paternal ages are lower in cases with BWCthan in ABS, although due to the sample sizes the dif-ferences do not reach the level of significance. Themean differences between paternal and maternal agesand the mean of the number of previous pregnanciesare similar in the 3 study groups.

On the other hand, among the infants with ABS withor without other congenital defects, all 32 cases inwhich the number of vessels in the umbilical cord isspecified, had 3 vessels. On the contrary, 7 out of 11cases with BWC with specified data, had only 2 vesselsin the umbilical cord (P 4 0.0003).

TABLE I. Study Population: Prevalences by Years

Year

Livebirths Stillbirths Total

N BirthsPrevalence

(1)a N BirthsPrevalence

(1)a N BirthsPrevalence

(1)a

1976 1 12,234 0.82 — — — — — —1977 0 27,426 — — — — — — —1978 2 35,533 0.56 — — — — — —1979 3 68,786 0.44 — — — — — —1980 10 60,289 1.66 0 562 — 10 60,851 1.641981 1 58,684 0.17 0 495 — 1 59,179 0.171982 4 69,080 0.58 0 539 — 4 69,619 0.571983 7 77,939 0.90 1 587 17.04 8 78,526 1.021984 3 72,642 0.41 2 542 36.90 5 73,184 0.681985 5 67,643 0.74 1 557 17.95 6 68,200 0.881986 5 57,769 0.87 1 476 21.00 6 58,245 1.031987 2 50,664 0.39 0 387 — 2 51,051 0.391988 5 52,278 0.96 0 408 — 5 52,686 0.951989 2 58,635 0.34 0 411 — 2 59,046 0.341990 2 83,759 0.24 0 620 — 2 84,379 0.241991 1 87,045 0.11 0 663 — 1 87,708 0.111992 2 91,032 0.22 0 575 — 2 91,607 0.221993 0 82,358 — 0 567 — 0 82,925 —1994 4 86,705 0.46 0 534 — 4 87,239 0.461995 3 86,842 0.35 1 530 18.87 4 87,372 0.461996 0 22,507 — 0 119 — 0 22,626 —

Total 62 1,309,850 0.47 6 8,572 7.00 62 1,174,443 0.53x2

20 4 39.50; P < 0.01 x216 4 15.25; Not significant x2

16 4 38.06; P < 0.005;Lineal trend: P < 0.0005

a(1) Prevalence per 10,000.

TABLE II. Sex Ratio by Study Group

Males Females M/F Total

Isolated ABS 21 33 0.76 58ABS with other

defects 6 4 1.5 10Body wall complex

(BWC) 14 10 1.4 24

Total livebirths 674,043 635,672 1.06 1,309,850

Amniotic Band Sequence 177

DISCUSSION

As stated in a previous paper [Martınez-Frıas, 1997],BWC is an etiologically heterogeneous entity with avariable clinical pattern, which is probably producedvery early during gestation. This early origin could ex-plain its clinical spectrum and its frequent associationwith blastogenetic defects. Its pathogenesis is also vari-able since it may be produced by vascular problems,amniotic defects including bands, etc. I also hypoth-esized that BWC is different from ABS without bodywall defects which may have a later developmental ori-gin, and which is also causally heterogeneous and clini-cally variable. I have compared these 2 entities in orderto determine if, from an epidemiological standpoint,they have different characteristics.

The present analysis showed that the characteristicsof the samples are different in infants with ABS and ininfants with BWC. Children with BWC are more fre-quently males, have lower birth weight, have a higherproportion of breech presentation, and their umbilicalcords more frequently have 2 vessels and are shorterthan in infants with ABS. In the same way, the parentsof infants with BWC are younger than the parents ofchildren with ABS. However, due to the sample size,only the figures for birth weight, length of the umbilicalcord, and the presence of only 2 vessels in the umbilicalcord, reach the level of statistical significance.

It is very difficult to compare the results of our epi-

demiological study with others from the literature, be-cause most publications involve clinical description ofcases, or consider cases with amniotic band defects re-gardless of whether they had a limb body wall complexor an amniotic band sequence without body wall in-volvement [Higginbottom et al., 1979; Seeds et al.,1982; Kalousek and Bamforth, 1988]. Some authors[Herva and Karkinen-Jaaskelainen, 1984; Delozier-Blanchet et al., 1985] used the classification of Ossipoffand Hall [1977] who considered 7 groups, but thesegroups include cases with both ABS and with BWC. Ina series of 13 consecutive cases of ABS described byBaker and Rudolph [1971], the mean of the birthweight was 2,810 g for a normal mean of gestationalage (39.2), birth weight being similar to that observedin the present study. Nevertheless, these authors ob-served a sex ratio of 1.17 (7/6). However, this sex ratiocould be influenced by the fact that they did not sepa-rate the children into isolated cases, and those withother anomalies. Kalousek and Bamforth [1988] de-scribed 18 previable fetuses with ABS, including 1 casewith BWC and another with omphalocele. These au-thors presented 2 groups, 1 with limb involvement only(11 fetuses) and the other with limb and other anoma-lies. The sex ratio in the first group (with isolated ABS)was 3/8 4 0.35, while the sex ratio of the second group(ABS associated to other defects) was 3/2 4 1.5 (ex-cluding the cases with BWC and omphalocele, bothmales). These results are concordant with those ob-served in the present study.

The reported prevalence for amniotic band defects(including BWC) varies from 1:1,234 [Ossipoff andHall, 1977] to 1:11,000 [Baker and Rudolph, 1971]. Ourfigures are lower since they are 1:21,127 for livebirthsand 1:18,943 for total births. However, these figuresshould be considered minimal estimates since we can-not totally exclude the effect of VIG. In fact, if we ana-lyze the prevalence of the period before 1986 (when theVIG was not legal in Spain), the prevalence figures are1:15,285 for livebirths and 1:12,046 for total births.Nevertheless, our lower prevalence figures are also in-fluenced by the exclusion of the BWC.

In conclusion, the results of the present analysis sug-

TABLE IV. Other Characteristics

YesN (%) No Total x2

2 P

Breech presentationIsolated ABS 6 (10.5) 51 57ABS with other defects 1 (11.1) 8 9 2.66 0.26Body wall complex (BWC) 6 (24) 19 25

Previous abortionsIsolated ABS 5 (8.6) 53 58ABS with other defects 2 (20) 8 10 2.92 0.23Body wall complex (BWC) 1 (3.2) 30 31

Vaginal bleedingIsolated ABS 17 (29.8) 40 57ABS with other defects 5 (50) 5 10 1.61 0.45Body wall complex (BWC) 9 (31.0) 20 29

TABLE III. Characteristics of the Children

Number Mean S.D. ANOVA

Birth weight (g)Isolated ABS 55 2,772.2 807.58 F 4 19.18ABS with other defects 8 2,809.3 827.56Body wall complex (BWC) 25 1,602 784.37 P < 0.01

Gestational age (weeks)Isolated ABS 55 36.91 3.55 F 4 1.76ABS with other defects 9 35.78 5.16Body wall complex (BWC) 29 35.36 3.52 P > 0.05, NS

Placental weight (g)Isolated ABS 17 507.1 179.6 F 4 0.15ABS with other defects 8 493.3 92.9Body wall complex (BWC) 25 467.2 181.5 P > 0.05, NS

Length umbilical cord (cm)Isolated ABS 8 50.88 F 4 7.03ABS with other defects 1 65Body wall complex (BWC) 4 16 P < 0.05

NS 4 not significant.

178 Martınez-Frıas

gest that ABS is an entity different from BWC. Thecases with BWC present significantly lower birthweight, and shorter umbilical cord with higher fre-quency of only 2 vessels. These characteristics togetherwith the high frequency of the presence of blastogeneticdefects in their clinical spectrum of anomalies [Mar-tınez-Frıas, 1997], suggest that their developmentalorigin is different and earlier than that of the ABSwithout body wall defects. Other characteristics, suchas parental ages, may also be lower in cases of BWCthan in cases with ABS. Thus, these results supportour previous proposal that BWC (cases with body walldefect associated with other malformations, deforma-tions or disruptions, regardless of their clinical patternand the possible etiology or pathogenetic mechanism)should be considered a different entity from ABS (in-fants with ring constrictions or amputations or disrup-tions with or without other congenital anomalies, butwithout body wall defects). Consequently, the amnioticbands in cases of BWC should be considered differentfrom amniotic bands in cases without body wall defects.The former are probably produced earlier in the devel-opment than the latter. In the present data, among the31 cases with BWC, only 5 had amniotic bands. Withan increasing number of cases we may eventually beable to compare the characteristics of infants withBWC and amniotic bands, with those of infants withABS without body wall defects, to better support thehypothesis that these 2 types of amniotic bands areproduced at different stages of development.

ACKNOWLEDGMENTSThis work was supported in part by a Grant from

Direccion General de Salud Publica del Ministerio deSanidad y Consumo of Spain, and by a grant from Fun-dacion 1000 para la investigacion sobre defectos con-genitos, of Spain. I wish to thank all the physicianswho collaborate with the ECEMC collecting the data.

REFERENCESBaker CJ, Rudolph AJ (1971): Congenital ring constrictions and intrauter-

ine amputations. Am J Dis Child 212:393–400.Chemke J, Graff G, Hurwitz N, Liban E (1973): Amniotic band syndrome.

Obstet Gynec 41:332.

DeLozier-Blanchet CD, Sohrabi-Zadeh N, Cox JN, Maye D, Engel E (1985):Amniotic band malformations. Praxis, Revue Suisse de Medicine 14:358–362.

Fiedler JM, Phelan JP (1983): The amniotic band syndrome in monozygotictwins. Am J Obstet Gynecol 146:864–865.

Herrmann J, Opitz JM (1974): Studies on Malformation Syndromes ofMan. IV. Naming and Nomenclature of Syndromes. March of DimesBirth Defects OAS X (7):69–86.

Herva R, Karkinen-Jaaskelainen M (1984): Amniotic adhesion malforma-tion syndrome: Fetal and placental pathology. Teratology 29:11–19.

Higginbottom MC, Jones KL, Hall BD, Smith DW (1979): The amnioticband disruption complex: Timing of amniotic rupture and variablespectra of consequent defects. J Pediatr 95:544–549.

Hunter AGW, Carpenter BF (1986): Implications of malformations not dueto amniotic bands in the amniotic band sequence. Am J Med Genet24:691–700.

Kalousek DK, Bamforth S (1988): Amnion rupture sequence in previablefetuses. Am J Med Genet 31:63–73.

Keller H, Neuhauser G, Durkin-Stamm MV, Kaveggia EG, Schaaff A, Sitz-mann F (1978): ADAM complex (Amniotic deformity, adhesion, muti-lations). A pattern of craniofacial and limb defects. Am J Med Genet2:81–98.

Kino Y (1975): Clinical and experimental studies of the congenital constric-tion band syndrome, with an emphasis on its etiology. J Bone JointSurg 57A:636.

Martınez-Frıas ML (1994): Epidemiological analysis of outcomes ofpregancy in diabetic mothers: Identification of the most characteristicand most frequent congenital anomalies. Am J Med Genet 51:108–113.

Martınez-Frıas ML (1995): Primary midline developmental field. I. Clinicaland epidemiological characteristics. Am J Med Genet 56:374–381.

Martınez-Frıas ML (1997): Clinical and epidemiological characteristics ofinfants with body wall complex (BWC) with and without limb defi-ciency. Am J Med Genet 73:170–175.

Martınez-Frıas ML, Urioste M (1994): Segmentation anomalies of the ver-tebras and ribs: A developmental field defect: Epidemiologic evidence.Am J Med Genet 49:36–44.

Ossipoff V, Hall BD (1977): Etiologic factors in the amniotic band syn-drome: A study of 24 patients. March of Dimes Birth Defects: OAS XIII,3D:117–132.

Pagon RA, Stephens TD, McGillivray BC, Diebert JR, Wright VJ, Hsu LL,Poland BJ, Emanuel I, Hall JG (1979): Body wall defects with reduc-tion limb anomalies: A report of fifteen cases. March of Dimes BirthDefects: OAS Vol XV, 5A:171–185.

Seeds JW, Cefalo RC, Herbert WNP (1982): Amniotic band syndrome. AmJ Obstet Gynecol 144:243–248.

Torpin R (1965): Amniochorionic mesoblast fibrous strings and amnioticbands. Am J Obstet Gynecol 91:65–75.

Van Allen MI, Curry C, Gallagher L (1987a): Limb body wall complex: I.Pathogenesis. Am J Med Genet 28:529–548.

Van Allen MI, Curry C, Walden CE, Gallagher L, Patten RM (1987b): Limbbody wall complex: II. Limb and spine defects. Am J Med Genet 28:549–565.

TABLE V. Characteristics of the Parents

Number Mean S.D. ANOVA

Maternal ageIsolated ABS 57 26.26 5.40 F 4 0.86ABS with other defects 10 26.20 5.19Body wall complex (BWC) 31 24.74 5.14 P > 0.05, NS

Paternal ageIsolated ABS 55 29.38 4.99 F 4 1.06ABS with other defects 8 29.25 3.46Body wall complex (BWC) 30 27.57 6.80 P > 0.05, NS

Mean differences betweenparental ages

Isolated ABS 55 3.24 4.00 F 4 0.29ABS with other defects 8 2.88 3.26Body wall complex (BWC) 30 2.57 3.84 P > 0.05, NS

Number of pregnanciesIsolated ABS 56 1.98 1.33 F 4 1.17ABS with other defects 10 1.60 0.66Body wall complex (BWC) 30 1.57 1.30 P > 0.05, NS

NS 4 not significant.

Amniotic Band Sequence 179