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Cranial defect repair using e-PTFE: part I. Evaluation of bone stiffness.

Autologous bone grafts are the preferred material for craniofacial reconstruction, but such procedures lead to increased operative time and bleeding, donor site morbidity, and graft resorption. The efficacy of expanded-polytetrafluoroethylene (e-PTFE) sheets to increase bone regeneration and remodeling in cranial defects using a rabbit model was evaluated by mechanical testing. New Zealand white rabbits were divided into 3 groups and sacrificed 6 months after surgery. In the Split Table group, (n = 16), a bilateral bone defect was created on the outer table of the parietal bones. In the Full Table group, (n = 16), a bilateral defect was created through both the inner and outer table of the cranium. The control group, (n = 10) was subjected to a sham operation. Indentation testing was performed to determine the stiffness of newly formed bone in and around the defect. Near the center of the defect, Split Table defects repaired with e-PTFE resulted in significantly stiffer bone than regenerated control bone. The Full Table defects repaired with e-PTFE also resulted in bone significantly stiffer than control regenerated bone around the central region of the defect. The data supports the hypothesis that e-PTFE improves the repair of cranial defects in a rabbit model. It is surmised that the porosity of the e-PTFE provides a stable scaffold for migration of tissue regenerating cells, which may be preferentially localized near the cranial suture lines. This porosity may also provide a barrier to fibrous tissue regenerating cells.

Animals↗

Missing osteoconductive effect of a resorbable PEO/PBT copolymer in human bone defects: a clinically relevant pilot study with contrary results to previous animal studies.

PEO/PBT 70/30 (POLYACTIVE(R) 70/30), a degradable porous copolymer with elastic properties, was found to be osteoconductive in many animal studies. The aim of this study was to determine the osteoconductive effect in a human paired control iliac defect model. In seven patients undergoing anterior spinal interbody fusion surgery, two bicortical iliac defects for autograft harvesting were created. The defect size was identical for both defects measuring about 40 x 15 mm (group I). One defect was filled with the degradable implants, whereas the remaining one was left untreated as a control. The defect site for treatment was chosen randomly. In three further patients, only one defect measuring about 40 x 35 mm was created (group II). All patients were examined clinically and radiologically by spiral-CT after 1, 6, 12, 24, and 52 weeks. Three-dimensional reconstructions as well as CT-volumetric measurements using 1 mm sections were used as evaluation methods. In group I, a two-tailed paired t-test showed that the treated defects had significantly less formation of new bone than the untreated ones (p < 0.05 after 12 weeks, p < 0.01 after 52 weeks). Also, in group II, not much bone ingrowth could be observed. The histological evaluation of one patient in group I revealed no bone within the pores, and a fibrous layer between bone and implant was always present. Therefore, PEO/PBT 70/30 cannot be recommended as a bone substitute for clinical use. Differences in bone regeneration between humans and certain animal species as well as inapplicable defect models in previous animal studies are discussed as possible reasons for the failure.

Animals↗

Interproximal contact hypoplasia in primary teeth: A new enamel defect with anthropological and clinical relevance.

This study reports the prevalence, distribution, and expression of enamel defects in a sample of primary teeth (n = 225) from a prehistoric site in western India (1400-700 BC). Five enamel surfaces of individual, isolated primary teeth were observed for surface defects using a binocular stereomicroscope with variable power of magnification (8-20x). Standards for evaluating dental enamel defects (DDE) recommended by the Fédération Dentaire International (FDI) were employed. Details of defect expression were also recorded, including size, shape, and surface of tooth crown affected. Hypoplastic enamel defects were observed in 28% of teeth, but the distribution and expression of defects was not random. More than 50% of canine teeth had hypoplastic defects (HD); incisors and molar teeth exhibited far fewer HD. The buccal surface of canines was the most commonly affected crown surface. Areas of missing enamel were also common on the mesial and distal surfaces of canines and incisors and on the mesial surface of molar teeth. The high frequency of enamel defects found on interproximal crown surfaces warrants a label, and the name interproximal contact hypoplasia (IPCH) is proposed. Linear enamel hypoplasia (LEH) was absent from this primary dental sample. IPCH is more frequent in mandibular than in maxillary teeth, but no side preference was detected. In canine teeth, buccal hypoplasias (localized hypoplasia of primary canines; LHPC) were not positively correlated with interproximal hypoplastic defects. The etiology of IPCH may involve mesial compaction of developing teeth due to slow longitudinal growth of the jaws. Episodic bone remodeling results in ephemeral fenestrae in the mesial and distal walls of the dental crypt permitting tooth-tooth contact and disruption of amelogenesis. IPCH prevalence decreases across the subsistence transition from sedentary Early Jorwe agriculturalists to seminomadic Late Jorwe hunters and foragers, but the difference is not statistically significant. This may be due to underrepresentation of mandibular teeth in the sample. Am. J. Hum. Biol. 11:718-734, 1999. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

Birth defects prevalence among infants of Persian Gulf War veterans born in Hawaii, 1989-1993.

BACKGROUND: Gulf War veterans (GWVs) have expressed concern about possible teratogenic exposures. However, epidemiologic studies on birth defects prevalence among their progeny have been limited to military hospitals, anomalies diagnosed among newborns, or self-reported data. To measure the prevalence of selected birth defects among infants of GWVs and nondeployed veterans (NDVs) in Hawaii, using birth defects surveillance records. METHODS: Personal identifiers of 684,645 GWVs and 1,587,102 NDVs and their families were matched against birth certificate records of 99,545 live births reported to the State of Hawaii Department of Health between 1989 and 1993 to identify births to military personnel. These births were matched with records from the Hawaii Birth Defects Program. RESULTS: A total of 17,182 military infants (3,717 GWV infants and 13,465 NDV infants) were identified. Of these, 367 infants (2.14/100 live births) were identified with one or more of 48 major birth defects diagnoses. The prevalence of the 48 birth defects were similar for GWV and NDV infants during the prewar and postwar periods, and among GWV infants who were conceived before and after the Gulf war. CONCLUSIONS: The results must be interpreted with caution because of the small number of affected infants in each birth defects category. This study demonstrated the feasibility of measuring birth defects prevalence among military infants through multiple data linkage. Further, it included live births to parents who had separated from the military, births in civilian hospitals, and birth defects diagnosed through the first year of life.

Adult↗

Quantitative analysis of associations between birth defects and suspected human teratogens.

Case series of infants with certain birth defect patterns and putative teratogenic exposures should be interpreted with caution since the presence of birth defects and the exposure among the same infants could be entirely due to chance. In the absence of other epidemiologic data, the plausibility for a causal association is strengthened by 1) rarity of the defect pattern, 2) rarity of the exposure in the population, 3) small source population, 4) short time period for the study, and 5) biologic plausibility for the association. These concepts are illustrated using case reports of putative teratogenicity of cocaine and etretinate. In the presence of epidemiologic data, the concept of attributable fraction in exposed (AFE) can be used to evaluate the likelihood that the defect pattern among infants with a particular exposure is attributable to the exposure. This quantity is related to the strength of the epidemiologic association between the defect pattern and the exposure, as measured in terms of relative risk R (or odds ratio), and is equal to (R-1)/R. Even for strong teratogens such as maternal diabetes and isotretinoin, where R is about 7, in more than 14% (1-AFE) of exposed infants with birth defects, the pattern of defects is not attributable to the exposure. Furthermore, AFE can be used to "correct" crude measures of sensitivity (the proportion of exposed malformed infants with a defect pattern attributable to the exposure) and positive predictive value (the proportion of malformed infants who have the exposure and have the defect pattern attributable to the exposure).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Vitamin supplements and the risk for congenital anomalies other than neural tube defects.

Randomized trials, supported by many observational studies, have shown that periconceptional use of folic acid, alone or in multivitamin supplements, is effective for the primary prevention of neural tube defects (NTDs). Whether this is true also for other congenital anomalies is a complex issue and the focus of this review. It is useful to consider the evidence not only for specific birth defects separately but, importantly, also for all birth defects combined. For the latter, the Hungarian randomized clinical trial indicated, for periconceptional multivitamin use, a reduction in the risk for all birth defects (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.35-0.70), even after excluding NTDs (OR = 0.53, 95% CI = 0.38-0.75). The Atlanta population-based case-control study, the only large observational study to date on all major birth defects, also found a significant risk reduction for all birth defects (OR = 0.80, 95% CI = 0.69-0.93) even after excluding NTDs (OR = 0.84, 95% CI = 0.72-0.97). These and other studies also evaluated specific anomalies, including those of the heart, limb, and urinary tract, as well as orofacial clefts, omphalocele, and imperforate anus. For cardiovascular anomalies, two studies were negative, whereas three, including the randomized clinical trial, suggest a possible 25-50% overall risk reduction, more marked for some conotruncal and septal defects. For orofacial clefts, six of seven case-control studies suggest an apparent reduced risk, which could vary by cleft type and perhaps, according to some investigators, by pill dosage. For limb deficiencies, three case-control studies and the randomized trial estimated approximately a 50% reduced risk. For urinary tract defects, three case-control studies and the randomized trial reported reduced risks, as did one study of nonsyndromic omphalocele. All these studies examined multivitamin supplement use. With respect to folic acid alone, a reduced rate of imperforate anus was observed among folic acid users in China. We discuss key gaps in knowledge, possible avenues for future research, and counseling issues for families concerned about occurrence or recurrence of these birth defects.

Adult↗

Retinotopic and directional defects in motion discrimination in humans with cerebral lesions.

We investigated the discrimination of motion direction in peripheral and central vision in 23 patients with unilateral cerebral hemispheric lesions on computed tomography or magnetic resonance imaging. We used random dot cinematograms that determined a percent coherence motion threshold for 16 points in the peripheral field and for four directions separately in central vision. We measured asymmetry of right- versus left-field peripheral discrimination (retinotopic defects) and asymmetry of central discrimination for rightward versus leftward motion (directional defects), compared with normal subjects. Five patients had directional asymmetries of foveal motion perception, all worse for motion toward the side of their lesions. One patient had a bidirectional defect for the perception of horizontal motion. For 3 of these 6, the average of all horizontal and vertical motion discrimination thresholds was also elevated. Two had contralateral retinotopic defects. One of these also had an ipsidirectional foveal defect, but the other did not. The remaining 5 patients with ipsidirectional foveal defects had hemianopias that precluded testing for coexistent retinotopic defects. The lesions of the 6 patients with ipsidirectional defects overlapped in white matter underlying the lateral temporo-occipital cortex, at the junction of Brodmann areas 19 and 37. In contrast, lesions of patients without directional defects spared this region.

Adult↗

Random error and undercounting in birth defects surveillance data: implications for inference.

BACKGROUND: There has been an ongoing debate among birth defects investigators about whether or not to publish estimates of rates of birth defects with confidence intervals to allow for comparisons of rates across regions and time. A major impediment in resolving this debate has been the lack of a framework for quantifying uncertainties in the data that can be applied uniformly to birth defects surveillance programs. This report presents an overview of random error and ascertainment bias in birth defects surveillance data, and of the implications of these errors for estimation and comparisons of birth defects rates. METHODS: We consider when confidence intervals can be used as part of a strategy to make inference on rates, as well as ratios of or differences between two rates. Worth noting is that confidence intervals only address random error in the data. In the presence of undercounting of cases, estimation of rates and confidence intervals requires knowledge or an estimate of the extent of underascertainment. Rate estimates and confidence intervals that ignore such bias can be misleading. However, if it is reasonable to assume that the ascertainment bias is constant over time (or across regions), then it is possible to make valid comparisons of rates over time (or across regions) using ratio or difference estimators, even when lack of knowledge of the extent of undercounting makes estimating the absolute rate and its confidence interval problematic. Finally, sensitivity analyses can use confidence limits to determine the difference in ascertainment bias necessary to explain an apparent difference in rates. CONCLUSION: Because birth defects surveillance systems have evolved in the absence of agreed upon standards to guide the process, it is difficult to determine the extent to which the variability in rates of birth defects across programs or over time is real or due to differences in surveillance methods. Efforts to develop standards for birth defects surveillance may help to minimize the variability in prevalence of birth defects due to differences in case ascertainment methods and allow for evaluations of real temporal and spatial variations in environmental effects. In the meantime, if comparisons of rates need to be made to address public health concerns, it would be prudent to conduct only such comparisons between regions or across time when the degree of case ascertainment can be assumed to be relatively constant across regions and time.

Birth Certificates↗

Sex differences in birth defects: a study of opposite-sex twins.

BACKGROUND: Sex differences in structural birth defects are often confounded by environmental risk factors. Opposite-sex twins provide a unique model for detecting sex differences in birth defects while maximally controlling environmental risk factors in a natural setting. METHODS: Population data from the Florida Birth Defects Registry were analyzed. A total of 4,768 pairs of twins who were discordant for sex and born between 1996 and 2001 were analyzed. The McNemar test was used to compare the differences between a male twin and his twin sister for the risk of developing specific defects and organ-system defects. RESULTS: Of 4,768 twin pairs, 225 males (4.72%) and 175 females (3.67%) had birth defects. Among opposite-sex twin pairs, males had a 29% higher risk for birth defects than their twin sisters. Compared to their twin sisters, males had a 5.4 times higher risk for pyloric stenosis and a 2.4 times higher risk for obstructive genitourinary defect, but only one-tenth the risk for congenital hip dislocation. CONCLUSIONS: Sex differences in birth defects exist between opposite-sex twins.

Congenital Abnormalities↗

Apatite-wollastonite containing glass ceramic-fibrin mixture as a bone defect filler.

The purpose of this study was to evaluate the usefulness of a mixture of apatite-wollastonite containing glass ceramic (A-W.GC, 42-60 mesh in granule size) with fibrin as a bone defect filler. A bone defect was drilled in the proximal metaphysis of the rat tibia and was filled with (1) fibrin glue, (2) A-W.GC granules, or (3) A-W.GC-fibrin mixture. Nothing was placed in the defect of the controls. The animals were serially sacrificed until 8 weeks after the operation, and the defect site was histologically examined and histomorphometrically analyzed for quantitative evaluation of newly formed bone and blood vessels. The use of fibrin glue as the binder markedly increased the ease of handling the A-W.GC granules. In the controls, little trabecular regeneration was observed in the defect site. Early vascularization (confirmed by microangiography) increased and the repairing process was accelerated in the defects filled with fibrin. In these defects filled with A-W.GC granules, good bone formation was observed around the granules. Bone formation was accelerated in the defects filled with A-W.GC fibrin mixture. Thus, the mixture showed good osteoconductive potential as well as acceleration of the repair process. Therefore, A-W.GC-fibrin mixture is considered to be a useful bone defect filler.

Animals↗

Comparison of demineralized allogeneic bone matrix grafting (the Urist procedure) and the Ilizarov procedure in large diaphyseal defects in sheep.

The bone inductive capability of the Urist and Ilizarov procedures was compared in the repair of large diaphyseal defects in sheep. In 30 animals, a 4 cm segmental defect was created in the middle portion of the right femur and was stabilized with an external fixator. The sheep were divided into four groups according to the type of reconstruction of the defect. In group 1, a demineralized allogeneic bone matrix (DABM) cylinder was used; in group 2, DABM chips; and in group 3, gradual transport of a piece of bone detached from the proximal femoral fragment was used to fill the defect. Group 4 served as a control (the defect was left empty). New bone formation was assessed by serial radiographs until the time of death at 2 or 4 months. Postmortem specimens were analyzed with respect to bone mineral content, uptake of isotopes (45Ca and 3H-proline), and histology. The first signs of new bone formation were radiographically evident at 4 weeks. In the two groups in which reconstruction involved DABM (Urist procedures), new bone failed to form in eight of the 13 animals. Full bridging of the defect was observed at 8 weeks in one animal with a DABM cylinder and two with DABM chips. No decisive difference in bone yield could be demonstrated between the two Urist procedures. In the group treated with the Ilizarov procedure, new bone formation consistently occurred at a high rate; full bridging of the defect was observed in seven of the eight animals. Bone mineral scanning and histologic analysis essentially confirmed the radiographic results. Uptake of isotopes was selectively analyzed in two sheep from each experimental group in which new bone formation was exhibited in the defect; new bone formation was increased compared with that in the contralateral femur but was equal among the three experimental groups. Our study shows that gradual transport of a detached piece of autogeneic bone (Ilizarov procedure) is more effective than implantation of DABM (Urist procedure) in eliciting new bone formation in large diaphyseal defects in sheep. The variable bone induction by DABM may be explained by differences in host immune responses to the implants.

Animals↗

Evaluation of bovine-derived bone protein with a natural coral carrier as a bone-graft substitute in a canine segmental defect model.

The efficacy of a bone-graft substitute (bovine-derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight-bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine-derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm3). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type-I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine-derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight-bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone represents a poor option as a bone-graft substitute in this critical-sized segmental defect model.

Animals↗

In vitro strength comparison of hydroxyapatite cement and polymethylmethacrylate in subchondral defects in caprine femora.

Hydroxyapatite cement was investigated in situ for the reconstruction of juxta-articular defects. Polymethylmethacrylate is currently the most commonly used material for the reconstruction of bone defects following the exteriorization and curettage of aggressive benign tumors. In vitro, we compared the effects of hydroxyapatite cement and polymethylmethacrylate in restoring the stiffness of the subchondral plate in a caprine femoral defect model. Ten matched pairs of caprine femora underwent nondestructive compression testing normal to the load-bearing surface. A standardized subchondral defect 12 mm in diameter was created in the medial femoral condyle. Compression testing was repeated to determine the reduction in stiffness caused by the defect. Each femur from each pair was randomly assigned to one of two groups (n=9), and the defects were augmented with either polymethylmethacrylate or hydroxyapatite cement. After 12 hours, compression testing was repeated to determine the subchondral stiffness after augmentation. Compared with intact femora, the defect specimens that were later treated with either polymethylmethacrylate or hydroxyapatite cement exhibited stiffness values of 70 (386+/-107 N/mm) and 59% (343+/-94 N/mm) respectively, which represented a significant reduction in stiffness (p=0.05). Augmentation with polymethylmethacrylate or hydroxyapatite cement restored stiffness by 81 (450+/-111 N/mm) and 71% (413+/-115 N/mm), respectively, of the values of intact specimens. Hydroxyapatite cement restored stiffness significantly (p=0.05) over the stiffness of the nonaugmented defect compared with the stiffness after augmentation with polymethylmethacrylate (p=0.12). Neither polymethylmethacrylate nor hydroxyapatite cement restored stiffness to that of intact femora (p=0.05). In the current detect model, hydroxyapatite cement was comparable with polymethylmethacrylate in restoring subchondral stiffness. Unlike polymethylmethacrylate, however, hydroxyapatite cement has the following advantages: it is osteoconductive, is replaced by host bone, and avoids the potential for thermal necrosis. Hydroxyapatite cement may therefore provide a viable alternative to polymethylmethacrylate for augmentation of juxta-articular and other bone defects.

Animals↗

New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy x-ray absorptiometry.

An appropriate animal model is required for the study of treatments that enhance bone healing. A new segmental long bone defect model was developed for this purpose, and dual energy x-ray absorptiometry was used to quantify healing of this bone defect. In 15 sheep, a 3-cm segmental defect was created in the left tibia and fixed with an interlocking intramedullary nail. In seven animals, the defect was left empty for the assessment of the spontaneous healing response. In eight animals serving as a positive control, autologous bone grafting was performed. After 12 weeks, healing was evaluated with radiographs, a torsional test to failure, and dual energy x-ray absorptiometry. The mechanical test results were used for the assessment of unions and nonunions. Radiographic determination of nonunion was not reliably accomplished in this model. By means of dual energy x-ray absorptiometry, bone mineral density and content were measured in the middle of the defect. Bone mineral density was 91+/-7% (mean +/- SEM) and 72+/-6% that of the contralateral intact tibia in, respectively, the autologous bone-grafting and empty defect groups (p = 0.04). For bone mineral content, the values were, respectively, 117+/-18 and 82+/-9% (p = 0.07). Torsional strength and stiffness were also higher, although not significantly, in the group with autologous bone grafting than in that with the empty defect. Bone mineral density and content were closely related to the torsional properties (r2 ranged from 0.76 to 0.85, p < or = 0.0001). Because interlocking intramedullary nailing is a very common fixation method in patients, the newly developed segmental defect model has clinical relevance. The interlocking intramedullary nail provided adequate stability without implant failure. This model may be useful for the study of treatments that affect bone healing, and dual energy x-ray absorptiometry may be somewhat helpful in the analysis of healing of this bone defect.

Absorptiometry, Photon↗

Use of a collagen-platelet rich plasma scaffold to stimulate healing of a central defect in the canine ACL.

The anterior cruciate ligament (ACL) of the knee fails to heal after primary repair. Here we hypothesize that a beneficial biologic repair response can be induced by placing a collagen-platelet rich plasma (collagen-PRP) material into a central ACL defect. A collagen-PRP scaffold was used to treat a central ACL defect in vivo. In the first experiment, the histologic response in treated and untreated defects was evaluated at 3 (n = 5) and 6 weeks (n = 5). In the second experiment, biomechanical testing of the treated ligaments (n = 8) was performed at 6 weeks and compared with the results of biomechanical testing of untreated defects at the same time-point (n = 6). The percentage filling of the defects in the treated ACLs was significantly higher at both the 3- and 6-week time-points when compared with the untreated contralateral control defects (50 +/- 21% vs. 2 +/- 2% at 3 weeks, and 43 +/- 11% vs. 23 +/- 11 at 6 weeks; all values mean +/- SEM. Biomechanically, the treated ACL defects had a 40% increase in strength at 6 weeks, which was significantly higher than the 14% increase in strength previously reported for untreated defects (p < 0.02). Placement of a collagen-PRP bridging scaffold in a central ACL defect can stimulate healing of the ACL histologically and biomechanically.

Animals↗

Effective coding in birth defects surveillance.

Effective coding is critical to data collected by birth defects surveillance programs because subsequent use of the data depends on storage and retrieval of cases using codes. Hence, careful consideration needs to be given to the coding process. The primary goal of coding is to accurately, completely, and concisely represent infants with birth defects. Coding procedures need to accommodate the objectives of the surveillance program; for example, programs that focus on research may require different coding procedures from those that focus on linking infants to services. Several challenges exist in coding birth defects, including the need to distinguish infants with multiple defects and syndromes from those with isolated defects, and the need for strategies to code suspected defects for which confirmation is not available. Selection of a coding system by a birth defects surveillance program is central to the utility of the data collected. Most programs use a modification of the International Statistical Classification of Diseases and Related Health Problems-based (ICD) systems. This paper addresses ICD-based systems and the modifications used by many birth defects surveillance programs and presents examples of the problems in interpreting birth defects data because of inappropriate coding.

Congenital Abnormalities↗

Review of drug-induced limb defects in mammals.

The objective of this paper was to illustrate the spectrum of possible limb malformations in mammals resulting from drug exposure. A bibliography of 171 papers from 20 journals was generated from which pertinent data (drug used, limb defects reported, predominant defect location) were tabulated. These data should provide a basis for predictions about types of defects that might be expected in further studies and for judging postulated drug-induced human limb defects. However, direct extrapolation to humans is inappropriate. The following trends were observed: 1) Distal limb defects (autopod) are almost twice as common as proximal limb defects (stylopod and zygopod). 2) Ectrodactyly is the single most common type of limb defect, accounting for over half of the autopod defects. 3) Ectrodactyly is almost twice as common in the hindlimb as in the forelimb. 4) Postaxial ectrodactyly is over twice as common as preaxial ectrodactyly in the forelimb, but preaxial ectrodactyly is four times more common in the hindlimbs. 5) Polydactyly occurs with approximately equal frequency in forelimbs and hindlimbs, and preaxial polydactyly is most common in both fore and hindlimbs. 6) Polymelia (supernumerary limbs) occurred in one case, and may have been a spurious result. 7) Either transverse hemimelia is greatly underreported in teratology studies or it essentially does not occur. We have concluded that, at least in some cases, acetazolamide, adenine, 1,7-dimethylxanthine, and xanthine derivative aminophylline, retinoic acid, acetoxy-methyl-methylnitrosamine, aspirin, and cadmium can all cause unilateral defects.

Abnormalities, Drug-Induced↗

Impact of including elective pregnancy terminations before 20 weeks gestation on birth defect rates.

BACKGROUND: The majority of U.S. birth defects surveillance programs do not include elective terminations before 20 weeks gestation among the pregnancy outcomes covered. To assess the impact of defects among elective terminations before 20 weeks gestation, data from a birth defects registry that does include terminations before 20 weeks gestation were analyzed. METHODS: Using information from the Texas Birth Defects Registry, the number of cases and rate of 49 conditions were analyzed in two ways: excluding defects detected among elective pregnancy terminations before 20 weeks gestation, and including defects among terminations before 20 weeks. RESULTS: By including defects detected among elective terminations before 20 weeks, the number of cases increased by five percent or greater for nine conditions: anencephaly (29%); spina bifida without anencephaly (13%); encephalocele (21%); Patau syndrome (19%); Edwards syndrome (11%); Down syndrome (6%); omphalocele (15%); gastroschisis (5%); and anophthalmia (7%). There was no impact for 27 conditions, for which there were no cases detected among elective terminations before 20 weeks. The greatest impact was observed for anencephaly; the rate of anencephaly increased from 2.76 to 3.56 per 10,000 live births when defects among elective terminations before 20 weeks were included. CONCLUSIONS: Excluding defects among elective terminations before 20 weeks results in counts and rates that are somewhat incomplete, especially for conditions that are more commonly detected and electively terminated before 20 weeks. The impact varies by condition.

Abortion, Induced↗