A changing pattern in the association of oral contraceptives and the different groups of congenital limb deficiencies.

A case-control study on different groups of isolated congenital limb deficiency was performed in a ten-year population-based and revised Hungarian data set. A higher rate of one contraceptive pill type with relatively high dose (ethynodiol diacetate 1.0 mg + ethinyloestradiol 0.05 mg) used in the periconceptional period was found in the mothers of cases with terminal transverse defect (adjusted relative odds 1.9 with 95% confidence interval of 1.1-3.4). This risk is minimised by the use of recent low-dose pills.

PIP: In Hungary, researchers analyzed 1975-1984 population-based and revised data on 537 children with isolated congenital limb deficiency (CLD) (i.e., cases with at least 1 affected limb) and data on 537 age-matched controls with no CLD. They wanted to determine the association between periconceptional use of oral contraceptives (OCs) and CLD. Personal examination and/or medical documents confirmed reported diagnoses. They separated the isolated CLD cases into terminal transverse CLD, amniogenic CLD, radial and tibial CLD, ulnar-fibular CLD, split hand and/or foot CLD, and intercalary CLD. Periconceptional use of Bisecurin (relatively high dose of 1 mg ethynodiol diacetate and 0.05 mg ethinyl estradiol) was significantly associated with terminal transverse CLD (adjusted odds ratio [AOR] = 1.9; p = 0.03). It was also significantly associated with monomelic CLD (AOR = 1.6; 9.6% vs. 2.9%; p = 0.0015). The monomelic cases comprised 19 terminal transverse cases, 6 amniogenic cases, 7 radial cases, 3 atypical split hand cases, and 2 ulnar cases. 19 of the 20 terminal transverse cases were monomelic. Periconceptional use of Continuin (0.5 mg ethynodiol diacetate alone) was associated, but not significantly so, with terminal transverse CLD (6 cases vs. 1 control; p = 0.06). These findings suggest that use of OCs with a high dose of ethynodiol diacetate increases the risk of terminal transverse defect. Use of low dose OCs likely minimizes this risk.

Smoking during pregnancy and congenital limb deficiency.

OBJECTIVE: To examine genetic and environmental factors in the origin of isolated congenital limb deficiencies. DESIGN: Case-control study with questionnaire at a family interview of cases of isolated congenital limb deficiencies (six types), negative controls (matched for age, sex, and place of residence), and positive controls (cases of sentinel anomalies). SETTING: The database of the Hungarian Congenital Abnormality Registry, 1975-84, complemented by three other sources of ascertainment (1,575,904 births). SUBJECTS: 537 case-control pairs; 392 positive controls. MAIN OUTCOME MEASURES: Smoking during pregnancy, congenital limb deficiencies. RESULTS: The adjusted rate of smoking during pregnancy was significantly higher in the mothers of cases of terminal transverse defect (relative odds 1.48; 95% confidence interval 0.98 to 2.23; P = 0.017). This finding supports the hypothesis of vascular disruption as a cause of congenital limb deficiency. CONCLUSIONS: Maternal smoking during pregnancy raises the relative odds for terminal transverse limb deficiencies.

A morphological and family study on isolated terminal transverse type of congenital limb deficiency in Hungary, 1975-1984.

A population-based and validated data set of 195 cases with isolated terminal transverse-type congenital limb deficiency was evaluated in Hungary, 1975-1984. Terminal transverse types of congenital limb deficiency are not usually associated with non-limb defects, and typically only one limb is affected. Upper limb is more frequently affected than lower (9:1) in monomelic cases. The left side and females are affected more often in upper limbs while lower limb defects are evenly distributed between right and left sides and both sexes. Familial occurrence was not found.

A family study on isolated congenital radial and tibial deficiencies in Hungary, 1975-1984.

Radial and tibial deficiencies are frequently (70%) associated with non-limb abnormalities. Isolated radial and tibial deficiencies may have a different etiology: in this study radial deficiencies were more frequent, there were milder subtypes and one-limb involvement was found in 70% of cases, tibial deficiencies were rare, mild subtypes did not occur and in general more limbs were involved. Among multimelic cases, one case had hypoplasia of the tibia with polydactyly and two cases had tibial aplasia with split hand +/- foot of autosomal dominant inheritance. Of 40 cases, four were familial. Findings of a case-control study on this population-based and validated 10-year cohort showed a lower mean birth weight and a higher rate of low birth weight in cases with isolated radial and tibial deficiency.

An epidemiological study of isolated split hand/foot in Hungary, 1975-1984.

A population based and validated 10 year cohort of 94 cases with split hand/foot born in Hungary, 1975-1984 was evaluated. This type of congenital limb deficiency was relatively frequently (43%) associated with non-limb defects. Fifty-four cases with isolated split hand/foot are evaluated in this paper. A single limb was affected in 78% of cases. The upper limbs were 21 times more frequently affected in unimelic cases with a right sided predominance and male excess. Case-control analysis indicated intrauterine growth retardation and lower socioeconomic status of parents of cases. Family study showed six familial cases with autosomal dominant inheritance among 152 first and 452 second degree relatives. All familial cases were males.

Study of isolated apparent amniogenic limb deficiency in Hungary, 1975-1984.

A population-based and validated data set of 206 cases with apparent amniogenic limb deficiency was ascertained in Hungary between 1975 and 1984. Such limb defects frequently (36%) associated with nonlimb abnormalities. In 134 cases with isolated defects typically more limbs are affected, upper and lower limbs, right and left sides, and both sexes are equally affected. Case-control analysis of such isolated cases indicates a lower socioeconomic status of parents, a higher parity, more frequent unwanted pregnancies, preterm birth, and a higher rate of threatened abortion. Familial occurrence was not found in 415 first-degree relatives.

Causal study of isolated ulnar-fibular deficiency in Hungary, 1975-1984.

A population-based and validated data set of 114 cases with isolated ulnar-fibular deficiency was evaluated in Hungary, 1975-1984. Ulnar-fibular type had the third most common birth prevalence (0.07 per 1000) among isolated congenital limb deficiency types. This type is relatively rarely associated with nonlimb defects, a single limb is affected in two-thirds of cases, nearly all other cases had femur-fibula-ulna (FFU) dysostosis. Upper and lower limbs, right and left sides, are equally affected, however, there is an obvious male excess (71%). Case-control analysis indicated a lower birth weight due to intrauterine growth retardation, higher birth order, lower socioeconomic status of parents, and a more frequent reported subfertility. The family study identified one familial cluster (one siboccurrence) among 331 first-degree relatives.

Etiological study on isolated proximal intercalary type of congenital limb deficiency in Hungary, 1975-1984.

A population-based and validated data set of 14 cases with isolated proximal intercalary type of congenital limb deficiency born in Hungary between 1975-84 was evaluated. Two cases had phocomelia of upper limbs, while 12 cases were affected with classical intercalary defects mainly in femurs. Of 14 cases, 13 had unimelic manifestation and both sexes were equally affected. The intrauterine growth retardation, the excess of second birth order, a higher rate of acute maternal disorder of the respiratory system and the lack of familial cluster are noteworthy. The vascular disruption hypothesis seems to be the most plausible explanation for the origin of isolated proximal intercalary defects.

Birth prevalence of different congenital limb deficiency types in a revised, population based Hungarian material, 1975-1984.

998 cases affected with limb reduction deficiency were evaluated in Hungary, 1975-1984. Through the check-up of other sources of ascertainments, the Hungarian Congenital Abnormality Registry was found to be 98.4% complete. The proportion of misdiagnoses was 12.6%. In the period encompassed by the study, the birth prevalence of revised cases affected with congenital limb reduction deficiency was 0.55 per 1000 total births. Isolated and multiple cases were separated. The birth prevalence of revised isolated cases was 0.35 per 1000. Six types were separated based on their phenotypic manifestations. As the number of affected limbs, ratio of isolated and multiple cases and sex ratio showed obvious differences, etiological factors should be evaluated separately in these different types of congenital limb deficiencies.