Transverse Limb Deficiencies Research Articles

Mobius Syndrome: A 35-Year Single Institution Experience.

Mobius syndrome is a rare syndrome that is known to be associated with a variety of orthopaedic conditions including scoliosis, clubfoot, transverse limb deficiencies, Poland syndrome, and a myriad of hand conditions. To date, no large series exist to characterize the orthopaedic manifestations of Mobius syndrome. Medical records at a single tertiary pediatric institution were reviewed for all patients diagnosed with Mobius syndrome from January 1, 1980 to December 31, 2015. Records and radiographs were reviewed for associated orthopaedic conditions and their management. In total, 44 patients with Mobius syndrome were identified. Age at presentation ranged from 6 days to 14 years. When compared with the general population, patients with Mobius syndrome had an increased incidence of clubfoot (41%), Poland syndrome (20%), and scoliosis (14%). Clubfoot treated both before and after the institution of Ponseti casting had a high rate of requiring posteromedial release, with a significant rate of subsequent revision. Hip dysplasia was noted in 1 patient and required surgical correction. Other associated syndromes included arthrogryposis, Pierre Robin syndrome, and chromosome 10 defect. Mobius syndrome is accompanied by an increased rate of several orthopaedic problems; most notably clubfoot, scoliosis, and upper extremity differences that often require surgical treatment. The management of clubfoot in the setting of Mobius syndrome often requires surgical intervention due to failure of casting, and seems to have a higher rate of need for revision. Early involvement of orthopaedists in the care of patients with Mobius syndrome is often necessary. Orthopaedist should counsel families that treatment may be more complex than that of idiopathic disease. Level IV-case series.

Antioxidant Consumption is Associated with Decreased Odds of Congenital Limb Deficiencies.

Approximately 1 in 2000 infants is born with a limb deficiency in the US. Research has shown that women's periconceptional diet and use of vitamin supplements can affect risk of birth defects. We investigated whether maternal consumption of nutritional antioxidants was associated with occurrence of transverse limb deficiency (TLD) and longitudinal limb deficiencies (LLD). We analysed case-control data from mothers and their singleton infants with TLD (n=566), LLD (n=339), or no malformation (controls; n=9384) in the National Birth Defects Prevention Study (1997-2009). Using a modified food frequency, we estimated usual pre-pregnancy antioxidant consumption by total fruit and vegetable consumption (in grams) grouped into tertiles, and cumulative antioxidant score (ranging from 1 to 10) based on consumption of three antioxidants: beta-carotene, lycopene, and lutein. We estimated odds ratios (OR) adjusted for maternal age, race/ethnicity, education, smoking, alcohol use, body mass index, and total energy. Compared to women in the lowest tertile of fruit and vegetable consumption, women in the highest tertile were less likely to have infants with TLD (OR 0.74, 95% CI 0.57, 0.96) or LLD (OR 0.82, 95% CI 0.59, 1.13). Compared to the lowest antioxidant consumption score of 1, those with the highest score of 10 had ORs of 0.68 (95% CI 0.48, 0.95) for TLD and 0.77 (95% CI 0.50, 1.17) for LLD. Dietary intake of antioxidants was associated with reduced odds of limb deficiencies. These findings add further evidence for women's periconceptional diet reducing occurrence of some birth defects.

Orthopedic Manifestations of Mobius Syndrome: Case Series and Survey Study.

Background. Mobius Syndrome is a rare disease defined by bilateral congenital 7th nerve palsy. We focus on reporting the prevalence of orthopedic disease in this population. Methods. Twenty-three individuals with Mobius Syndrome underwent orthopedic physical examination, and additional 96 patients filled out a survey for self-reported orthopedic diagnoses. Results. Clubfoot was present in 60% of individuals in the physical exam series and 42% of those in the survey. Scoliosis was present in 26% and 28%, respectively. Poland's Syndrome was present in 17% and 30%. In addition to these findings, 27% of patients reported having difficulty with anesthesia, including difficulty in intubation and airway problems. Conclusion. An increased prevalence of scoliosis, clubfoot, transverse limb deficiencies, and Poland's Syndrome is identified in the setting of Mobius Syndrome. In the setting of several deformities often requiring surgical correction, a high incidence of anesthetic difficulty is noted and should be discussed with patients and other providers during surgical planning.

Residential agricultural pesticide exposures and risks of selected birth defects among offspring in the San Joaquin Valley of California.

We examined associations of birth defects with residential proximity to commercial agricultural pesticide applications in California. Subjects included 367 cases representing five types of birth defects and 785 nonmalformed controls born 1997 to 2006. Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for covariates. Overall, 46% of cases and 38% of controls were classified as exposed to pesticides within a 500 m radius of mother's address during a 3-month periconceptional window. We estimated odds ratios (ORs) for 85 groups and 95 chemicals with five or more exposed cases and control mothers. Ninety-five percent confidence intervals (CI) excluded 1.0 for 11 ORs for groups and 22 ORs for chemicals, ranging from 1.9 to 3.1 for groups and 1.8 to 4.9 for chemicals except for two that were <1 (noted below). For groups, these ORs were for anotia/microtia (n = 95 cases) and dichlorophenoxy acids/esters and neonicotinoids; anorectal atresia/stenosis (n = 77) and alcohol/ethers and organophosphates (these ORs were < 1.0); transverse limb deficiencies (n = 59) and dichlorophenoxy acids/esters, petroleum derivatives, and triazines; and craniosynostosis (n = 79) and alcohol/ethers, avermectins, neonicotinoids, and organophosphates. For chemicals, ORs were: anotia/microtia and five pesticides from the groups dichlorophenoxy acids/esters, copper-containing compounds, neonicotinoids, organophosphates, and triazines; transverse limb deficiency and six pesticides - oxyfluorfen and pesticides from the groups copper-containing compounds, 2,6-dinitroanilines, neonicotinoids, petroleum derivatives and polyalkyloxy compounds; craniosynostosis and 10 pesticides - oxyfluorfen and pesticides from the groups alcohol/ethers, avermectins, n-methyl-carbamates, neonicotinoids, ogranophosphates (two chemicals), polyalkyloxy compounds (two chemicals), and pyrethroids; and congenital diaphragmatic hernia (n = 62) and a copper-containing compound.

Routine screening for fetal limb abnormalities in the first trimester.

We aim to determine the accuracy of first-trimester ultrasonography in detecting fetal limb abnormalities. This is a retrospective study of all women undergoing fetal nuchal translucency (NT) assessment and detailed fetal anatomic survey in the first trimester at a single tertiary-care referral center in China. Fetal anatomy scans were repeated in the second trimester. Detection of fetal limb abnormalities was compared between first and second trimester anatomy scans and confirmed at delivery or at autopsy. Analyzed were 9438 fetuses from 9197 women (241 twin pairs). The incidence of fetal limb abnormalities was 0.38% (36/9438). Of these, 28 (77.8%) were diagnosed prenatally: 23 (63.9%) on first trimester scan and 5 (13.9%) on second trimester scan. Limb reduction defects (usually transverse limb deficiencies) were the most common limb defects identified in the first trimester (n = 12), followed by clubfoot (n = 4), skeletal dysplasia (n = 3), sirenomelia (n = 1), limb dysplasia (n = 1), malposition (n = 1), and syndactyly (n = 1). Nine fetuses with isolated limb abnormalities had normal NT, while 74.1% (20/27) of limb abnormalities that were associated with other abnormalities had increased NT. This study demonstrates that the majority of limb abnormalities detected prenatally [23/28 (82%)] can be identified in the first trimester, especially major limb defects; however, our numbers are small and still need larger cases for further investigation.

Meromelia in a Newborn- A Rare Congenital Anomaly

A term, 2.6 kg, female child was born of a non consanguineous marriage to a primigravida via vaginal mode at the authors' institute. The child had major limb anomalies at birth. The right leg showed terminal transverse limb deficiency just below the knee joint while there was terminal transverse deficiency at distal third of left forearm (Fig. 1). Rest of the systemic examination was normal. Ultrasound head, abdomen and 2D echocardiography were normal. Family history and antenatal history (including drug intake, radiation exposure, febrile illness and rash) were negative. The antenatal ultrasound was done in first trimester only which was normal. The baby was asymptomatic and attached to pediatric orthopedic unit for rehabilitation and prosthesis at a later stage. Limb defects are described as meromelia (partial absence) or amelia (complete absence) of one or more limbs. Phocomelia is a type of meromelia where rudimentary hands or feet are attached to trunk by small, irregularly shaped bones. The international society for prosthetics and orthotics (ISPO) classification describes limb deficiencies as either transverse (no distal skeletal remainsas index case) or longitudinal (has distal portions) [1]. Etiological factors include genetic, teratogens (infamous-thalidomide use), vascular disruptions and ischemia, chemicals and radiation exposure [2]. Children with limb anomalies have associated malformations like craniofacial, gastrointestinal, heart, kidney and nervous system. The present case was unique that child had only isolated limb meromelia with no other congenital anomalies. Contributions PM: Drafted the manuscript and reviewed the literature; DC: Revised the manuscript and managed the case. He will act as guarantor for this paper.

Traffic‐related air pollution and selected birth defects in the San Joaquin Valley of California

Birth defects are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some structural anomalies, although evidence is limited and several anomalies have not been investigated previously. We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 26 congenital birth defect phenotypes with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997 to 2006 (874 cases and 849 controls). We calculated odds ratios (adjusted for maternal race/ethnicity, education, and vitamin use; aOR) for 11 phenotypes that had at least 40 cases. Few odds ratios had confidence intervals that did not include 1.0. Odds of esophageal atresia were increased for the highest versus lowest of traffic density (aOR = 2.8, 95% confidence interval [CI], 1.1-7.4) and PM10 exposure (aOR 4.9; 95% CI, 1.4-17.2). PM₁₀ was associated with a decreased risk of hydrocephaly (aOR= 0.3; 95% CI, 0.1-0.9) and CO with decreased risk of anotia/microtia (aOR = 0.4; 95% CI, 0.2-0.8) and transverse limb deficiency (aOR = 0.4; 95% CI, 0.2-0.9), again reflecting highest versus lowest quartile comparisons. Most analyses showed no substantive association between air pollution and the selected birth defects with few exceptions of mixed results.

Maternal periconceptional occupational exposure to pesticides and selected musculoskeletal birth defects

This population-based U.S. study investigated the association between major musculoskeletal malformations and periconceptional maternal occupational pesticide exposure for a wide range of occupations. We conducted a multi-site case-control analysis using data from the National Birth Defects Prevention Study among employed women with due dates from October 1, 1997 through December 31, 2002. Cases included 871 live-born, stillborn, or electively terminated fetuses with isolated craniosynostosis, gastroschisis, diaphragmatic hernia, or transverse limb deficiencies. Controls included 2857 live-born infants without major malformations. Using self-reported maternal occupational information, an industrial hygienist used a job-exposure matrix and expert opinion to evaluate the potential for exposure to insecticides, herbicides or fungicides for each job held during one month pre-conception through three months post-conception. Exposures analyzed included any exposure (yes/no) to pesticides, to insecticides only, to both insecticides and herbicides (I+H) and to insecticides, herbicides and fungicides (I+H+F). We used logistic regression to evaluate the association between exposures and defects, controlling for infant and maternal risk factors. Occupational exposure to I+H+F was associated with gastroschisis among infants of women aged 20 years or older (adjusted odds ratio [aOR]=1.88; 95% confidence interval [CI]: 1.16-3.05), but not for women under age 20 (aOR=0.48; 95% CI: 0.20-1.16). We found no significant associations for the other defects. Additional research is needed to validate these findings in a separate population.

Dietary Glycemic Index and the Risk of Birth Defects

The importance of obesity and diabetes in the development of birth defects is a major concern. Prepregnancy obesity and diabetes are independent risk factors for congenital heart, neural tube, and gastrointestinal defects; hyperglycemia and hyperinsulinemia likely have a causal role in the process. This study was undertaken to investigate the association between dietary glycemic index (DGI) and various birth defect phenotypes among nondiabetic women and the impact of obesity on this association. The National Birth Defects Prevention Study is an ongoing, multisite, case-control study that collects data on more than 30 structural birth defects. Cases among live births, fetal deaths, and electively terminated pregnancies were identified through surveillance systems in several states. Controls were nonmalformed, live-born infants randomly selected from birth certificates/hospital records. Maternal interviews were conducted within 2 years of the estimated date of delivery. Data on demographics, medication use, lifestyle behaviors, and health conditions were collected. One component of the interview was the shortened Willett food frequency questionnaire in which mothers recalled their average consumption of 58 different foods in the year before pregnancy. Data from this questionnaire were used to calculate DGI and dietary glycemic load. The analysis was restricted to determining the association between DGI and birth defects. The cutoff point was the DGI value that corresponded with a divergence of cases and controls at an odds ratio (OR) of 1.5. Dietary glycemic index was divided into quartiles based on the distribution among controls for each birth defect group. Case groups for which spline regression identified a divergence were assessed for interdependence between high DGI and obesity. The analysis included 7505 controls and 18,964 cases among 53 case groups. Compared with mothers in the lowest DGI quartile, those in the highest quartile were more likely to be non-Hispanic black, younger than 25 years, have 12 years of education or less, and less likely to take folic acid. A prepregnancy body mass index of either less than 18.5 kg/m2 or 30 kg/m2 or greater was also associated with the highest DGI quartile. Encephalocele was the only CNS defect significantly associated with high DGI (adjusted OR [aOR] = 2.68). Spina bifida had an increased but not statistically significant aOR of 2.15. For gastrointestinal and genitourinary defects, the odds of esophageal atresia with or without tracheoesophageal fistula and anorectal atresia/stenosis, which was significant, were 32% and 40% higher in the highest quartile of DGI compared with the lowest quartile. Small intestinal atresia/stenosis and duodenal atresia/stenosis were significantly associated with high DGI. The odds of biliary atresia increased with each quartile of DGI resulting in an aOR of 1.69 in the highest quartile. Bladder exstrophy had an aOR of 4.10. Obesity with high DGI had a larger positive association with small intestinal atresia and duodenal atresia than high DGI without obesity. Most congenital heart defects were not significantly associated with quartiles of DGI. The odds of aortic stenosis and heterotaxia with a congenital heart defect increased with each quartile of DGI resulting in an aOR of 1.29 and 1.55 for those in the highest DGI quartile, respectively. Other birth defects significantly associated with high DGI were transverse limb deficiency, diaphragmatic hernia, and gastroschisis. Among infants of nondiabetic women, high levels of DGI were associated with neural tube, gastrointestinal, and musculoskeletal defects, but not with various heart defects. These results offer evidence for the role of hyperglycemia in abnormal fetal development. Hyperinsulinemia with hyperglycemia might intensify the effect on the risk of birth defects compared with hyperglycemia alone. The findings highlight the interdependence of high DGI and obesity, which act synergistically. Future research using biologic samples could contribute to the understanding of the role of hyperglycemia and hyperinsulinemia in the development of birth defects.

An additional family with association of hereditary thrombocytosis and transverse limb deficiency: Confirmation of a rare clinical spectrum

American Journal of Medical Genetics Part AVolume 158A, Issue 12 p. 3211-3213 Research Letter An additional family with association of hereditary thrombocytosis and transverse limb deficiency: Confirmation of a rare clinical spectrum† Claudio Graziano, Corresponding Author Claudio Graziano [email protected] Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, ItalyMedical Genetics Unit, Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy.Search for more papers by this authorMichèle David, Michèle David Division of Hematology–Oncology, CHU Sainte-Justine, Montreal, CanadaSearch for more papers by this authorPamela Magini, Pamela Magini Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, ItalySearch for more papers by this authorAndrea Superti-Furga, Andrea Superti-Furga University of Lausanne, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandSearch for more papers by this authorMarco Seri, Marco Seri Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, ItalySearch for more papers by this author Claudio Graziano, Corresponding Author Claudio Graziano [email protected] Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, ItalyMedical Genetics Unit, Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy.Search for more papers by this authorMichèle David, Michèle David Division of Hematology–Oncology, CHU Sainte-Justine, Montreal, CanadaSearch for more papers by this authorPamela Magini, Pamela Magini Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, ItalySearch for more papers by this authorAndrea Superti-Furga, Andrea Superti-Furga University of Lausanne, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandSearch for more papers by this authorMarco Seri, Marco Seri Medical Genetics Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, ItalySearch for more papers by this author First published: 19 November 2012 https://doi.org/10.1002/ajmg.a.35656Citations: 2 † How to Cite this Article: Graziano C, David M, Magini P, Superti-Furga A, Seri M, 2012. An additional family with association of hereditary thrombocytosis and transverse limb deficiency: Confirmation of a rare clinical spectrum. Am J Med Genet Part A 158A: 3211–3213. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume158A, Issue12December 2012Pages 3211-3213 RelatedInformation

Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations.

Nitrosatable drugs can react with nitrite in the stomach to form N-nitroso compounds, and results from animal studies suggest that N-nitroso compounds are teratogens. With data from the National Birth Defects Prevention Study, the relation between prenatal exposure to nitrosatable drugs and limb deficiencies, oral cleft, and heart malformations in offspring was examined. Maternal reports of drugs taken during the first trimester of pregnancy were classified with respect to nitrosatability for mothers of 741 babies with limb deficiencies, 2774 with oral cleft malformations, 8091 with congenital heart malformations, and 6807 without major congenital malformations. Nitrite intake was estimated from maternal responses to a food frequency questionnaire. Isolated transverse limb deficiencies and atrioventricular septal defects were associated with secondary amine drug exposures (adjusted odds ratios [aORs], 1.51; 95% confidence limit [CI], 1.11-2.06 and aOR, 1.97; 95% CI, 1.19-3.26, respectively). Tertiary amines were associated with hypoplastic left heart syndrome (aOR, 1.50; 95% CI, 1.10-2.04) and single ventricle (aOR, 1.61; 95% CI, 1.06-2.45). These two malformations were also significantly associated with amide drugs. For several malformations, the strongest associations with nitrosatable drug use occurred among mothers with the highest estimated dietary nitrite intake, especially for secondary amines and atrioventricular septal defects (highest tertile of nitrite, aOR, 3.30; 95% CI, 1.44-7.58). Prenatal exposure to nitrosatable drugs may be associated with several congenital malformations, especially with higher nitrite intake. The possible interaction between nitrosatable drugs and dietary nitrite on risk of congenital malformations warrants further attention.

Nonsteroidal antiinflammatory drug use among women and the risk of birth defects

We examined whether the use of nonsteroidal antiinflammatory drugs (NSAIDs) in early pregnancy was associated with a range of structural birth defects. Data were from the National Birth Defects Prevention Study, a multisite population-based, case-control study of risk factors for birth defects. Among women in the National Birth Defects Prevention Study, 22.6% reported the use of NSAIDs in the first trimester of pregnancy, most commonly ibuprofen, aspirin, and naproxen. Of the 29 defect groups that were examined, most were not associated with NSAID use. Small-to-moderate increased risks of some oral cleft groups, some neural tube defect groups, anophthalmia/microphthalmia, pulmonary valve stenosis, amniotic bands/limb body wall defects, and transverse limb deficiencies were associated with ibuprofen, aspirin, and naproxen exposure. The use of NSAIDs in early pregnancy does not appear to be a major risk factor for birth defects, although there were a few moderate associations between NSAIDs and specific birth defects.

Maternal self-reported genital tract infections during pregnancy and the risk of selected birth defects

Genital tract infections are common during pregnancy and can result in adverse outcomes including preterm birth and neonatal infection. This hypothesis-generating study examined whether these infections are associated with selected birth defects. We conducted a case-control study of 5913 children identified as controls and 12,158 cases with birth defects from the National Birth Defects Prevention Study (1997-2004). Maternal interviews provided data on genital tract infections that occurred from one month before pregnancy through the end of the first trimester. Infections were either grouped together as a single overall exposure or were considered as a subgroup that included chlamydia/gonorrhea/pelvic inflammatory disease. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with adjustment for potential confounders. Genital tract infections were associated with bilateral renal agenesis/hypoplasia (OR, 2.89; 95% CI, 1.11-7.50), cleft lip with or without cleft palate (OR, 1.46; 95% CI, 1.03-2.06), and transverse limb deficiency (OR, 1.84; 95% CI, 1.04-3.26). Chlamydia/gonorrhea/pelvic inflammatory disease was associated with cleft lip only (OR, 2.81; 95% CI, 1.39-5.69). These findings were not statistically significant after adjustment for multiple comparisons. Caution is needed in interpreting these findings due to the possible misclassification of infection, the limited sample size that constrained consideration of the effects of treatment, and the possibility of chance associations. Although these data do not provide strong evidence for an association between genital tract infections and birth defects, additional research on the possible effects of these relatively common infections is needed.

Folic acid flour fortification: Impact on the frequencies of 52 congenital anomaly types in three South American countries

The aim of the present investigation was to search for a reduction in birth prevalence estimates of 52 selected types of congenital anomalies, associated with folic acid fortification programs in Chile, Argentina, and Brazil. The material included 3,347,559 total births in 77 hospitals of the three countries during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341 (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared pre- and post-fortification rates within each hospital and the resulting Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant reductions in birth prevalence estimates after fortification were observed for neural tube defects (NTDs), septal heart defects, transverse limb deficiencies, and subluxation of the hip. However, only the reduction of NTDs appeared to be associated with folic acid fortification and not due to other factors, because of its consistency among the three countries, as well as with previously published reports, and its strong statistical significance. Among the NTDs, the maximum prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and cephalocele. This observation suggests etiologic and pathogenetic heterogeneity among different levels of spina bifida, as well as among different NTD subtypes. We concluded that food fortification with folic acid prevents NTDs but not other types of congenital anomalies.

Periventricular nodular heterotopia and distal limb deficiency: A recurrent association

Malformations of cerebral cortical development, in particular periventricular nodular heterotopia (PNH), and distal transverse limb deficiency have been reported as associated congenital anomalies. Patients with PNH and transverse limb deficiency can be classified as having amniotic band sequence or Adams-Oliver syndrome (AOS). Controversy exists whether these should be considered separate entities. In some AOS patients, autosomal recessive inheritance has been shown, but in most patients causes are unknown, and both environmental and genetic factors have been implicated. We present three patients with PNH and distal transverse limb deficiency to support the hypothesis that these should be considered part of one group of disorders, and highlight the variable severity of the clinical and neuroradiological phenotype. Chromosome abnormalities were excluded by copy number analysis on 250K SNP microarray data.Research done on limb deficiency as on PNH caused by mutations in known genes, suggests the involvement of vascular developmental pathways. The combination of limb deficiency and PNH may have a common causative mechanism. Recognition and grouping of patients with this combination of abnormalities will help elucidating the cause.

Antibacterial Medication Use During Pregnancy and Risk of Birth Defects

To estimate the association between antibacterial medications and selected birth defects. Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.

Maternal nutrient intake and risks for transverse and longitudinal limb deficiencies: Data from the National Birth Defects Prevention Study, 1997–2003

The association between periconceptional intake of supplements containing folic acid with specific subtypes of limb deficiencies has been inconsistent. The objective was to investigate whether intake of nutrients involved in one-carbon metabolism (folate, vitamin B(6), vitamin B(12), riboflavin, choline, betaine, zinc, and methionine) through diet alone or in combination with a supplement containing folic acid influenced the risk for transverse limb deficiency (TLD) and longitudinal limb deficiency (LLD). We analyzed 1997-2003 data from the National Birth Defects Prevention Study and included 324 case infants with TLD, 158 case infants with LLD, and 4982 nonmalformed control infants. A food frequency questionnaire was used to estimate nutrient intakes. Use of supplements containing folic acid 1 month before through 2 months after conception was recorded. Use of a supplement containing folic acid was not associated with LLD or TLD. For nonsupplement users, within (1) the lowest quartile of dietary folate intake or vitamin B(6) intake, adjusted odds ratios (aORs) for LLD were, respectively, 3.86 (95% confidence interval [CI]: 1.08-13.78) and 4.36 (95% CI: 0.93-20.48); and (2) the lowest quartile for riboflavin intake, the aOR for TLD was 2.94 (95% CI: 1.04-8.32). For supplement users within the lowest quartile of folate intake or riboflavin intake, the aORs for TLD were, respectively, 1.52 (95% CI: 0.91-2.54) and 1.54 (95% CI: 1.00-2.37). TLD and LLD were not associated with supplement use, but TLD was associated with low intakes of riboflavin from diet.

Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects

Limb reduction deficiencies that are accompanied by amniotic bands (AB-Ls) and terminal transverse limb deficiencies (TLDs) have each been attributed to vascular disruption; for the former, however, it is not clear if amniotic bands are the primary cause of or are secondary to vascular disruption. If amniotic bands are secondary to vascular disruption, then a shared pathogenesis for each case group might be exhibited by similar risk factors. We evaluated maternal age, education, race/ethnicity, parity, pregnancy wantedness, and vasoactive exposures among 139 AB-L and 373 TLD cases, using interview data collected from mothers in 10 states by the National Birth Defects Prevention Study. Vasoactive exposures included maternal cigarette smoking and use of decongestants, nonsteroid anti-inflammatory drugs, and antihypertensive drugs in the periconceptional period. Increased risk estimates were observed for Black mothers (OR 2.5; 95% CI: 1.5-4.1) and nulliparous mothers (2.1; 1.4-3.0) in relation to AB-L, while neither was associated with TLD. Hispanic women (1.4; 1.0-1.9) and those not wanting the pregnancy (1.5; 1.1-2.1) had increased risks of TLD, but not AB-L. Maternal cigarette smoking and aspirin use each increased the risk of AB-L, but not TLD; while decongestants and possibly antihypertensive medications increased the risk of TLD, but not AB-L. The lack of consistent findings for the two case groups suggests that AB-L and TLD may be distinct entities. The inconsistencies also suggest that these vasoactive exposures may not be markers for vascular disruption or that vascular disruption may not play a major role in the pathogenesis of these two types of limb deficiencies.

Descriptive epidemiologic features shared by birth defects thought to be related to vascular disruption in Texas, 1996–2002

In utero vascular disruptions are thought to be associated with a variety of birth defects. This study examined the descriptive epidemiology of several of those defects using data from a large birth defects registry. Data on birth defects ascertained from pregnancies in 1996-2002 were obtained from the Texas Birth Defects Registry. Using Poisson regression, we calculated crude and adjusted associations between maternal and infant characteristics and birth defects thought to be related to vascular disruption. We repeated the analysis using isolated cases and cases occurring in mothers <20 years. The most commonly shared pattern was observed for plurality and five defects: large intestinal atresia (PR 3.67; CI: 1.63-7.13), renal agenesis (PR 2.05; CI: 1.55-2.65), transverse limb deficiency (PR 1.85; CI: 1.28-2.57), porencephaly (PR 5.18; CI: 2.40-9.87), and Goldenhar syndrome (PR 3.45; CI: 1.04-8.53). Hispanics had the highest prevalence of gastroschisis (PR 1.21; CI: 1.05-1.40), transverse limb deficiency (PR 1.19; CI: 1.01-1.40), microtia/anotia (PR 2.22; CI: 1.83-2.70), and Poland anomaly (PR 1.90; CI: 1.26-2.93). Male infants were at greatest risk for renal agenesis (PR 1.58; CI: 1.40-1.80), porencephaly (PR 1.66; CI: 1.03-2.72), and Poland anomaly (PR 1.52; CI: 1.05-2.21). Our study confirmed findings in previous studies, but also uncovered several new associations.

Handless, footless fetus

We report a fetus with symmetrical terminal transverse limb deficiency. Two earlier reports described patients with similar defects. These patients resemble the animal models that result from the removal of apical ectodermal ridge.