Limb Reduction Defects Research Articles

Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility

Roberts/SC phocomelia syndrome (RBS/SC) is a rare autosomal recessive inherited condition characterized by prenatal-onset growth retardation, craniofacial anomalies, and symmetrical limb reduction defects. Here, we present two affected siblings with RBS/SC who have consanguineous parents. Both patients had intrauterine growth retardation; similar facial findings, including arched eyebrows, epicanthic folds, posteriorly angulated ears, and retrognathia; and hypopigmented patches on their skin. However, despite these common findings, the extremity involvement was different between the patients. The more severely affected boy had hypoplasia of the tibia and symmetrical agenesis of the radius, ulna, proximal carpal bones, and fibula. The slightly affected girl presented with mild symmetrical mesomelic shortening. The cytogenetic analysis showed aneuploidies at varying rates concerning different chromosomes in the analyses of different culture materials. As a remarkable finding in the cytogenetic studies, chromosome analysis of fibroblast cultures obtained from the hypopigmented skin region showed a much higher frequency of aneuploidy, especially trisomy 7, than normopigmented skin fibroblasts and lymphocyte cultures for both patients, which was also proven ex vivo by qPCR analyses from uncultured skin tissues. In the subsequent ESCO2 gene sequence analysis, both patients were found to be homozygous for the mutation c.1111dupA (p.Thr371Asnfs*32; NM_001017420.2), which is known to be pathogenic. In the literature search, only two RBS/SC patient reports with hypopigmented skin patches could be found. In addition, the presence of pigmentation defects in the embryo was reported in some different animal models for RBS/SC. When the literature review and study are evaluated together, hypopigmented patches can be considered as a rare finding for RBS/SC. It can be suggested that somatic aneuploidies seen in the natural course of the disease, especially aneuploidy of chromosome 7, which has many genes associated with pigmentation, may be responsible for the hypopigmentation patches.

Trends in congenital anomalies in Europe from 1980 to 2012.

BackgroundSurveillance of congenital anomalies is important to identify potential teratogens.MethodsThis study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980–2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models.ResultsSeventeen anomaly subgroups had statistically significant trends from 2003–2012; 12 increasing and 5 decreasing.ConclusionsThe annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.

Morphology of early intrauterine deaths with full trisomy 15.

The morphologic features of embryos with full trisomy 15 are described. A total of 1195 pregnancy losses were examined embryoscopically and cytogenetically. Of 1173 successfully karyotyped specimens, full trisomy 15 was diagnosed cytogenetically in 59 cases (5%). All 59 trisomy 15 embryos were diagnosed cytogenetically in the group of 962 embryonic miscarriages (6%). Trisomy 15 was not registered in 171 anembryonic or yolk sac miscarriages, and no case of full trisomy 15 was observed in 62 fetal miscarriages. Fifty-eight embryos with full trisomy 15 showed structural defects on embryoscopic examination. The most common defects were craniofacial anomalies (n=73), retarded development of the limbs (n=39), and abnormally short umbilical cords closely attaching the embryo to the chorionic plate (n=27). Seven embryos were classified as growth disorganized. Limb reduction defects with a prevalence of 5.6/10000 births, all affecting upper limb development (10 terminal transverse limb reduction defects and 3 embryos with split hand), were registered in 13 (22%) trisomy 15 embryos. Limb reduction defects and craniofacial abnormalities are a typical feature of trisomy 15. Gene dosage imbalances related to trisomy 15 might be the main molecular mechanism underlying the developmental defects observed in the present study and require further investigation.

Metformin in the first trimester and risks for specific birth defects in the National Birth Defects Prevention Study.

We assessed associations between first-trimester metformin use for pregestational diabetes and specific major birth defects. We compared risks associated with first-trimester metformin use by diabetic women to nondiabetic women on no diabetes medication; we calculated crude odds ratios by exact logistic regression and adjusted by inverse probability weighting. Confounding by diabetes was assessed by comparing risks for metformin-exposed diabetic women to those for insulin-exposed diabetics and nondiabetics treated with metformin for subfertililty. Among 9,279 nonmalformed controls and 24,375 malformed cases, diabetics who used metformin (with or without insulin) had increased adjusted odds ratios (aORs) for several birth defects associated with diabetes. However, women treated with metformin for subfertility had aORs similar to or lower than those for diabetic metformin users, and many approximated the null. For atrial septal defect secundum, anorectal defects, and limb reduction defects, the estimates for metformin when used for subfertility were 2-3-fold. While metformin use for diabetes was associated with an increased risk of many birth defects, when metformin was used for subfertility most defects had aORs that approximated the null, while only three defects had modestly increased aORs, two of which had lower confidence bounds that included the null. Our study does not suggest that metformin poses an appreciable risk for major birth defects, but further studies are necessary.

Novel mosaic variants in two patients with Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a dominantly inherited developmental disorder caused by mutations in genes that encode for either structural (SMC1A, SMC3, RAD21) or regulatory (NIPBL, HDAC8) subunits of the cohesin complex. NIPBL represents the major gene of the syndrome and heterozygous mutations can be identified in more than 65% of patients. Interestingly, large portions of these variants were described as somatic mosaicism and often escape standard molecular diagnostics using lymphocyte DNA.Here we discuss the role of somatic mosaicism in CdLS and describe two additional patients with NIPBL mosaicism detected by targeted gene panel or exome sequencing. In order to verify the next generation sequencing data, Sanger sequencing or pyrosequencing on DNA extracted from different tissues were applied. None of the pathogenic variants was originally detected by Sanger sequencing on blood DNA.Patient 1 displays an unusual combination of clinical features: he is cognitively only mildly affected, but shows severe limb reduction defects. Patient 2 presents with a moderate phenotype. Interestingly, Sanger sequencing analysis on fibroblast DNA of this patient did not detect the disease-causing variant previously observed on the same DNA sample by exome sequencing. Subsequent analyses could confirm the variants by Sanger sequencing on buccal mucosa DNA. Notably, this is the first report of a higher mutational load in buccal mucosa than in fibroblast cells of a CdLS patient.Detection of low-level mosaicism is of utmost importance for an accurate molecular diagnosis and a proper genetic counseling of patients with a clinical diagnosis of CdLS. Next-generation sequencing technologies greatly facilitate the detection of low-level mosaicism, which might otherwise remain undetected by conventional sequencing approaches.

Maternal report of fever from cold or flu during early pregnancy and the risk for noncardiac birth defects, National Birth Defects Prevention Study, 1997-2011.

As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects. We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal self-report of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects. Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied. This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections.

Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene-environment interactions.

To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self-reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N = 1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of delivery were between 1997 and 2009. For each exposure and birth defect, odds ratios and 95% confidence intervals were calculated using logistic regression stratified by race-ethnicity and sample collection status. Tests for interaction were applied to identify potential differences between estimated measures of association based on sample collection status. Significant differences in estimated measures of association were observed in only four of 48 analyses with sufficient sample sizes. Despite lower than desired participation rates in buccal cell sample collection, this validation provides some reassurance that the estimates obtained for sample collectors and noncollectors are comparable. These findings support the validity of observed associations in gene-environment interaction studies for the selected exposures and birth defects among NBDPS participants who submitted DNA samples.

Early Gestational Hypoxia and Adverse Developmental Outcomes.

Hypoxia is a normal and essential part of embryonic development. However, this state may leave the embryo vulnerable to damage when oxygen supply is disturbed. Embryofetal response to hypoxia is dependent on duration and depth of hypoxia, as well as developmental stage. Early postimplantation rat embryos were resilient to hypoxia, with many surviving up to 1.5 hr of uterine clamping, while most mid-gestation embryos were dead after 1 hour of clamping. Survivors were small and many had a range of defects, principally terminal transverse limb reduction defects. Similar patterns of malformations occurred when embryonic hypoxia was induced by maternal hypoxia, interruption of uteroplacental flow, or perfusion and embryonic bradycardia. There is good evidence that high altitude pregnancies are associated with smaller babies and increased risk of some malformations, but these results are complicated by increased risk of pre-eclampsia. Early onset pre-eclampsia itself is associated with small for dates and increased risk of atrio-ventricular septal defects. Limb defects have clearly been associated with chorionic villus sampling, cocaine, and misoprostol use. Similar defects are also observed with increased frequency among fetuses who are homozygous for thalassemia. Drugs that block the potassium current, whether as the prime site of action or as a side effect, are highly teratogenic in experimental animals. They induce embryonic bradycardia, hypoxia, hemorrhage, and blisters, leading to transverse limb defects as well as craniofacial and cardiovascular defects. While evidence linking these drugs to birth defects in humans is not compelling, the reason may methodological rather than biological. Birth Defects Research 109:1358-1376, 2017.© 2017 Wiley Periodicals, Inc.

Evaluation of the Sensitivity and Accuracy of Birth Defects Indicators on the 2003 Revision of the U.S. Birth Certificate: Has Data Quality Improved?

The 2003 revision of the U.S. Birth Certificate was restricted to birth defects readily identifiable at birth. Despite being the lone source of birth defects cases in some studies, we lack population-based information on the quality of birth defects data from the most recent revision of the birth certificate. We linked birth certificate data to confirmed cases from the Florida Birth Defects Registry (FBDR) to assess the sensitivity and positive predictive value (PPV) of birth defects indicators on the birth certificate. Descriptive statistics and log-binomial regression were used to examine variation in data quality measures by defect type and other characteristics. We also evaluated the contribution of birth certificates as a case ascertainment source for the FBDR. Sensitivity of the birth certificate was poor (19.1%) with variation across defects ranging from 55% for anencephaly and 54% for gastroschisis, to <10% for other defects. PPV was better (87.1%) and ranged from >93% for orofacial clefts and gastroschisis to <55% for anencephaly and limb reduction defects. We also observed variation in data quality across maternal, infant, and hospital characteristics. Of cases identified by the birth certificate and not any other FBDR data source, 54.9% were false-positive diagnoses. Efforts to restrict the 2003 revision of the birth certificate to defects identifiable at birth have not improved the likelihood that birth certificates will identify infants born with those defects. We do not recommend the use of birth certificates as a source of birth defects data without case verification strategies.

Limb reduction defect due to failed misoprostol induced termination of pregnancy

On examination of the neonate, he had normal cry, reflex, colour and tone. Child had reduced left leg with absence of tibia and fibula, gross reduction of left femur, rotated left foot and syndactyly of left foot. (Figures1 and 2). On doing a digital x-ray of the neonate we found the radiological features matching the clinical picture (Figure 3). ___________________________________________ Junior Resident, Associate Professor, Department of Paediatrics, Junior Resident, Department of Obstetrics and Gynaecology, MKCG Medical College, India *Correspondence: dr.subham.scb@gmail.com (Received on 20 May 2015: Accepted after revision on 17 July 2015) The authors declare that there are no conflicts of interest Personal funding was used for this project.

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.

Associated congenital anomalies among cases with Down syndrome

Down syndrome (DS) is the most common congenital anomaly widely studied for at least 150 years. However, the type and the frequency of congenital anomalies associated with DS are still controversial. Despite prenatal diagnosis and elective termination of pregnancy for fetal anomalies, in Europe, from 2008 to 2012 the live birth prevalence of DS per 10,000 was 10. 2. The objectives of this study were to examine the major congenital anomalies occurring in infants and fetuses with Down syndrome. The material for this study came from 402,532 consecutive pregnancies of known outcome registered by our registry of congenital anomalies between 1979 and 2008. Four hundred sixty seven (64%) out of the 728 cases with DS registered had at least one major associated congenital anomaly. The most common associated anomalies were cardiac anomalies, 323 cases (44%), followed by digestive system anomalies, 42 cases (6%), musculoskeletal system anomalies, 35 cases (5%), urinary system anomalies, 28 cases (4%), respiratory system anomalies, 13 cases (2%), and other system anomalies, 26 cases (3.6%). Among the cases with DS with congenital heart defects, the most common cardiac anomaly was atrioventricular septal defect (30%) followed by atrial septum defect (25%), ventricular septal defect (22%), patent ductus arteriosus (5%), coarctation of aorta (5%), and tetralogy of Fallot (3%). Among the cases with DS with a digestive system anomaly recorded, duodenal atresia (67%), Hirschsprung disease (14%), and tracheo-esophageal atresia (10%) were the most common. Fourteen (2%) of the cases with DS had an obstructive anomaly of the renal pelvis, including hydronephrosis. The other most common anomalies associated with cases with DS were syndactyly, club foot, polydactyly, limb reduction, cataract, hydrocephaly, cleft palate, hypospadias and diaphragmatic hernia. Many studies to assess the anomalies associated with DS have reported various results. There is no agreement in the literature as to which associated anomalies are most common in cases with DS with associated anomalies. In this study we observed a higher percentage of associated anomalies than in the other reported series as well as an increase in the incidence of duodenal atresia, urinary system anomalies, musculoskeletal system anomalies, and respiratory system anomalies, and a decrease in the incidence of anal atresia, annular pancreas, and limb reduction defects. In conclusion, we observed a high prevalence of total congenital anomalies and specific patterns of malformations associated with Down syndrome which emphasizes the need to evaluate carefully all cases with Down syndrome for possible associated major congenital anomalies.

Invasive Prenatal Diagnosis: Chorionic Villus Sampling

ABSTRACT Chorionic villus sampling (CVS) is the method of choice for first trimester invasive prenatal diagnosis. In expert hands, it is nowadays considered as safe as amniocentesis and has the advantage of an earlier diagnosis. In this review, we describe the technique of the procedure, its indications and contraindications and the requirements concerning adequate training and optimum clinical practice. We also discuss issues concerning the safety of the procedure in singleton and multiple pregnancies, other complications and controversies, such as the association with limb reduction defects and pre-eclampsia, as well as diagnostic problems and dilemmas, such as maternal cell contamination and confined placental mosaicism. We also describe new and promising methods of non-invasive diagnosis, based on the isolation and analysis of fetal cells or cell-free fetal genetic material from the maternal circulation, that aim to replace the invasive methods of prenatal diagnosis in the future. How to cite this article Sindos M, Malamas FM, Antsaklis P, Antsaklis A. Invasive Prenatal Diagnosis: Chorionic Villus Sampling. Donald School J Ultrasound Obstet Gynecol 2015; 9(3):293-306.

Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome

Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the presence of aplasia cutis congenita (ACC) of the scalp vertex and terminal limb-reduction defects. Cardiovascular anomalies are also frequently observed. Mutations in five genes have been identified as a cause for AOS prior to this report. Mutations in EOGT and DOCK6 cause autosomal-recessive AOS, whereas mutations in ARHGAP31, RBPJ, and NOTCH1 lead to autosomal-dominant AOS. Because RBPJ, NOTCH1, and EOGT are involved in NOTCH signaling, we hypothesized that mutations in other genes involved in this pathway might also be implicated in AOS pathogenesis. Using a candidate-gene-based approach, we prioritized DLL4, a critical NOTCH ligand, due to its essential role in vascular development in the context of cardiovascular features in AOS-affected individuals. Targeted resequencing of the DLL4 gene with a custom enrichment panel in 89 independent families resulted in the identification of seven mutations. A defect in DLL4 was also detected in two families via whole-exome or genome sequencing. In total, nine heterozygous mutations in DLL4 were identified, including two nonsense and seven missense variants, the latter encompassing four mutations that replace or create cysteine residues, which are most likely critical for maintaining structural integrity of the protein. Affected individuals with DLL4 mutations present with variable clinical expression with no emerging genotype-phenotype correlations. Our findings demonstrate that DLL4 mutations are an additional cause of autosomal-dominant AOS or isolated ACC and provide further evidence for a key role of NOTCH signaling in the etiology of this disorder.

Congenital limb deficiencies in Alberta-a review of 33 years (1980-2012) from the Alberta Congenital Anomalies Surveillance System (ACASS).

The birth prevalence of limb deficiencies in Alberta has been fluctuating. The objectives were to examine patterns and temporal trends of congenital limb deficiencies in Alberta and compare rates with those of other jurisdictions. The Alberta Congenital Anomalies Surveillance System data on live births, stillbirths, and terminations of pregnancy (<20 weeks gestation) occurring between 1980 through 2012 with the ICD-10 Royal College of Paediatrics and Child Health Adaptations codes Q71-Q73 (limb reduction defects), Q79.80 (congenital constriction bands), and Q87.24 (sirenomelia syndrome) were reviewed. Cases were classified as having amelia, transverse, longitudinal (preaxial, postaxial, central, or mixed), intercalary, split hand/split foot, complex, or other type of limb deficiency. Phenotypes were classified as associated, which included cases with a known etiology and cases with at least one other type of anomaly, or isolated. From 1980 through 2012, 795 cases were ascertained from 1,411,652 live births and stillbirths, giving a prevalence of 5.6/10,000 total births. Mixed longitudinal deficiencies were the most common (22.4%). The upper limbs (63.9%) were affected more often than the lower limbs (25.3%). Isolated limb deficiencies occurred in 43.6% of cases, 28.4% had Mendelian or other known conditions, 21.9% had multiple congenital anomalies, 5.4% had chromosome abnormalities and 0.6% were due to teratogens. The associated group, showed a significant increasing trend (P = 0.023). While the overall limb deficiency rates show very little differences across diverse populations and differing time periods, comparisons of subgroups should be made with caution, because variations in terminology and classification contribute to reported differences.

Prenatal Detection of Upper Limb Differences With Obstetric Ultrasound

To determine the sensitivity, specificity, and predictive values of prenatal ultrasound detection of fetal upper extremity anomalies at a single tertiary care center in a large patient cohort. Our secondary purpose was to assess factors affecting prenatal detection including the presence of associated anomalies. We performed a retrospective review of prenatal ultrasound and postnatal clinical records from each pregnancy evaluated with a prenatal ultrasound at the Washington University Department of Obstetrics and Gynecology over a 20-year period. We searched for upper extremity anomaly diagnosis codes pre- and postnatally and correlated with clinical postnatal follow-up to determine prevalence, sensitivity, specificity, predictive values, and associated conditions. A total of 100,856 pregnancies were evaluated by prenatal ultrasound, which included 843 fetuses diagnosed with a musculoskeletal anomaly (prevalence, 1 of 120) and 642 with an upper extremity anomaly (prevalence, 1 of 157). The postnatally confirmed sensitivity for prenatal ultrasound detection of an upper extremity anomaly was 42%. Sensitivity was lower in cases isolated to the upper extremity (25% vs 55%). Sensitivity was highest for conditions affecting the entire upper extremity (70%-100%) and lowest for those affecting the digits alone (4%-19%). Fetuses with limb reduction defects, radial longitudinal deficiency, phocomelia, arthrogryposis, abnormal hand positioning, and cleft hand had a higher likelihood of having an associated anomaly. At our tertiary referral center, there was a notable prevalence of upper extremity anomalies; however, the overall sensitivity for detecting them with prenatal ultrasound was low. This was disappointing given the value of prenatal identification of anomalies for parental counseling. Prenatal diagnosis of anomalies affecting the entire upper limb was more reliable than diagnosis of more distal anomalies. Diagnostic III.

Pharmacoepidemiology and thalidomide embryopathy surveillance in Brazil.

Thalidomide causes congenital defects in children, such as limb reduction defects. Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported. We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil. A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) per 10,000 births. Poisson regression showed an increase in cases of TEP and limb reduction defects per 100,000 tablets dispensed. Clusters and geographical isolates were identified in several regions. There is a correlation between thalidomide and TEP showing that thalidomide embryopathy should be monitored in countries where this medication is available.

The utility of ultrasound for the detection of fetal limb abnormalities--a 20-year single-center experience.

ObjectiveThe standard obstetric ultrasound examination includes documentation of arms and legs. The purpose of this study is to review the efficacy of ultrasound for the detection of limb anomalies, the type and incidence of associated malformations and pregnancy outcomes.MethodAll cases of polydactyly (POD), abnormal hand position (AHP), limb reduction defects (LRD) and arthrogryposis (ART) scanned in our Unit between 1990 and 2010 were identified. Cases were categorized as isolated (ISO) or non-isolated (NISO). The accuracy of prenatal diagnosis, type and incidence of associated malformations and aneuploidy and pregnancy outcomes were determined.ResultsMost cases were NISO. The sensitivity of ultrasound was 19.1% for POD, 76.0% for AHP, 76.0% for LRD involving the long bones and 81.3% for ART. Cardiothoracic and facial defects were the most common accompanying malformations. The risk for aneuploidy ranged from 3.6% for POD to 47.2% for AHP. The live birth rate ranged from 85.5% for POD to 24.5% for AHP.ConclusionWhile imaging of the arms and legs allows detection of most cases of AHP, LRD involving the limbs and ART, a probable minimum of 20% to 25% of cases will escape prenatal diagnosis. Identification of these defects should prompt an extended anatomic survey and consideration of invasive testing for aneuploidy. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.

Factors associated with major structural birth defects among newborns delivered at Muhimbili National Hospital and Municipal Hospitals in Dar Es Salaam, Tanzania 2011 - 2012.

IntroductionNinety-four percent of all birth defects and 95% of deaths due to the birth defects occur in low and middle income countries, Tanzania among them. In Tanzania there are currently limited birth defects prevention strategies in place due to limited information on factors associated with the occurrence of birth defects.MethodsWe conducted a case control study that included newborns born from October, 2011 through February, 2012 at 4 participating hospitals. A case was defined as any newborn of a Dar es salaam resident with a neural tube defect, orofacial clefts, limb reduction defects or musculo-skeletal defects (SBD) born during the study period. A control was defined as the next three newborns (delivered after the case) without birth defects. Univariate, bivariate and multivariate analysis were done using Epi Info version 3.5.1.ResultsA total of 400 newborns participated in the study, 100 cases and 300 controls. Factors associated with higher odds of a SBD included maternal fever (adjusted odds ratio (AOR) = 1.99; 95% confidence interval (CI): 1.14-3.52), maternal hypertension (AOR = 3.99; 95% CI: 1.67-9.54), and low birth weight (AOR = 3.48; 95% CI: 1.77-6.85). Antimalarial use during pregnancy was protective (AOR = 0.48; 95% CI: 0.28-0.84). Folic acid supplementation was protective only in bivariate analysis (OR = 0.56; 95% CI: 0.32-0.96).ConclusionMaternal fever, hypertension, and low birth weight are associated with higher odds of SBD. Antimalarial use during pregnancy was associated with lower odds of SBD. Early screening of pregnant mothers for hypertension and other causes of low birth weight may reduce SBD in Dar Es Salaam.

Residential Radon Levels and Birth Defects

INTRODUCTION Maternal exposure to ionizing radiation has been associated with chromosomal anomalies in offspring, as well as with oral clefts, limb reduction defects, and polydactyly. We investigat...