Substantial incidence of bladder dysfunction in patients with VACTERL association: Implications for surveillance.

VACTERL association is defined as the nonrandom co-occurrence of a minimum of three of the following six key components: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Patients presenting with two components may also belong in the same spectrum. Additional components have been associated with VACTERL defects, including single umbilical artery, tethered spinal cord (TSC), and genital malformations. We observed a significant proportion of patients with bladder dysfunction (often called neurogenic bladder in the medical record) when reviewing a cohort of patients with VACTERL defects at our clinical center. Our finding calls attention to bladder dysfunction as an additional VACTERL phenotypic component. The prevalence of bladder dysfunction is greatest in those with genital anomalies, anorectal malformations, sacral dysplasia, renal anomalies, and TSC. We propose that patients with two or more VACTERL malformations be monitored for symptoms of bladder dysfunction if one or more of the identified risk factors are present until the achievement of urinary continence.

Neurodevelopmental outcomes in individuals with VACTERL association. A population-based cohort study.

BACKGROUND: Studies on neurodevelopmental outcomes in individuals with congenital anomalies who undergo neonatal surgery are scarce and have reported contradictory findings based on small study groups. The congenital condition VACTERL association includes at least three malformations: vertebral anomalies, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal anomalies and limb deformities. Most of these patients undergo surgery during their first days of life. Neurodevelopmental disorders include a broad group of disabilities involving some form of disruption to brain development. Attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability (ID) are diagnoses included in this group. The aim of the study was to investigate the risk of ADHD, ASD and ID in a cohort of individuals with VACTERL association. METHOD: Data was obtained from four Swedish national health registers and analyzed using the Cox proportional hazards model. Patients born 1973-2018 in Sweden with the diagnosis of VACTERL association were included in the study. For each case five healthy controls matched for sex, gestational age at birth, birth year and birth county were obtained. RESULTS: The study included 136 individuals with VACTERL association and 680 controls. Individuals with VACTERL had significantly higher risk of ADHD, ASD and ID than the controls; 2.25 (95% CI, 1.03-4.91), 5.15 (95% CI, 1.93-13.72) and 8.13 (95% CI, 2.66-24.87) times respectively. CONCLUSIONS: A higher risk of ADHD, ASD and ID was found among individuals with VACTERL association compared to controls. These results are of importance to caregivers and to professionals participating in follow ups of these patients in providing early diagnosis and support, aiming to optimize the quality of life of these patients.

Screening for VACTERL Anomalies in Children with Anorectal Malformations: Outcomes of a Standardized Approach.

PURPOSE: The majority of patients with an anorectal malformation (ARM) have associated congenital anomalies. It is well established that all patients diagnosed with an ARM should undergo systematic screening, including renal, spinal, and cardiac imaging. This study aimed to evaluate the findings and completeness of screening, following local implementation of standardized protocols. METHODS: A retrospective cohort study was performed assessing all patients with an ARM managed at our tertiary pediatric surgical center, following a standardized protocol implementation for VACTERL screening (January 2016-December 2021). Cohort demographics, medical characteristics, and screening investigations were analyzed. Findings were compared with our previously published data (2000-2015), conducted prior to protocol implementation. RESULTS: One hundred twenty-seven (64 male, 50.4%) children were eligible for inclusion. Complete screening was performed in 107/127 (84.3%) children. Of these, one or more associated anomalies were diagnosed in 85/107 (79.4%), whilst the VACTERL association was demonstrated in 57/107 (53.3%). The proportion of children that underwent complete screening increased significantly in comparison with those assessed prior to protocol implementation (RR 0.43 [CI 0.27-0.66]; p < 0.001). Children with less complex ARM types were significantly less likely to receive complete screening (p = 0.028). Neither presence of an associated anomaly, nor prevalence of the VACTERL association, differed significantly by ARM type complexity. CONCLUSION: Screening for associated VACTERL anomalies in children with ARM was significantly improved following standardized protocol implementation. The prevalence of associated anomalies in our cohort supports the value of routine VACTERL screening in all children with ARM, regardless of malformation type. LEVEL OF EVIDENCE: II.

Prevalence pattern, phenotypic manifestation, and descriptive genetics of congenital limb deficiencies in Pakistan.

BACKGROUND: Congenital limb deficiency (CLD) is a group of very rare disorders characterized by substantial hypoplasia or the complete absence of 1 or more bones of limbs. Congenital limb deficiency has a significant physical, clinical, and psychological burden on the affected individuals and their families. This cross-sectional study aimed to describe the prevalence pattern, phenotypic manifestations, and biodemographic factors associated with CLD in a cohort assembled from the Pakistani population from the Northwestern region. METHODS: Through a prospective cross-sectional study, 141 individuals having 166 limbs with CLD were recruited during 2017-2021. RESULTS: There were 77 (55%) individuals with transverse defects, 61 (43%) with longitudinal defects, and 3 (2%) with Intercalary defects. Among the patients with transverse defects, 52 had terminal amputations and 25 had symbrachydactyly. Among the longitudinal defects, thumb aplasia/hypoplasia was the most common presentation (20 patients), followed by oligodactyly (18), and radial hemimelia (18). Eighty six percent had upper-limb deficiencies, 83% had unilateral deficiencies, and 92% were sporadic in nature. The parental consanguinity was observed in 33% individuals, and 79% cases had an isolated presentation which may be indicative of the substantial role of nongenetic factors in the etiology of CLD. CONCLUSIONS: This study demonstrates marked heterogeneity in CLD subtypes in the involvement of limbs and associated variables. There is a need to establish a national registry for CLD, molecular genetic diagnosis, and multidisciplinary medical and social rehabilitation services for these individuals.

The Importance of Screening for Additional Anomalies in Patients with Anorectal Malformations: A Retrospective Cohort Study.

BACKGROUND: In children with anorectal malformations (ARM), additional anomalies can occur within the VACTERL-association. Routine screening is of great importance for early identification and potential treatment. However, uniformity in screening protocols is lacking and only small cohorts have been described in literature. The aim of this study was to assess and describe a unique large cohort of ARM patients who underwent VACTERL screening in the neonatal period. METHODS: A retrospective mono-center cohort study was performed. Included were all neonates born between January 2000 and December 2020 who were diagnosed with ARM and screened for additional anomalies. Full screening consisted of x-ray and ultrasound of the spine, cardiac and renal ultrasound, and physical examination for limb deformities, esophageal atresia, and ARM. Criteria for VACTERL-classification were predefined according to the EUROCAT-definitions. RESULTS: In total, 216 patients were included, of whom 167 (77.3%) underwent full VACTERL-screening (66% in 2000-2006 vs. 82% in 2007-2013 vs. 86% in 2014-2020). Median age at follow-up was 7.0 years (IQR 3.0-12.8). In 103/167 patients (61.7%), additional anomalies were identified. Some 35/216 patients (16.2%) fulfilled the criteria of a form of VACTERL-association. In 37/216 patients (17.1%), a genetic cause or syndrome was found. CONCLUSIONS: The majority of ARM patients underwent full screening to detect additional anomalies (77%), which improved over time to 86%. Yet, approximately a quarter of patients was not screened, with the potential of missing important additional anomalies that might have severe consequences in the future. Forms of VACTERL-association or genetic causes were found in 16% and 17% respectively. This study emphasizes the importance of routine screening. LEVEL OF EVIDENCE: III.

Does presence of a VACTERL anomaly predict an associated gynecologic anomaly in females with anorectal malformations?: A Pediatric Colorectal and Pelvic Learning Consortium Study.

BACKGROUND: VACTERL association is defined by the presence of 3 or more anomalies in any of the following systems: vertebral, anorectal, cardiac, trachea-esophageal, renal, or limb. This study hypothesized that the presence of VACTERL association would correlate with an increased risk of gynecologic anomalies in patients with anorectal malformation (ARM). METHODS: This study is a cross-sectional, retrospective analysis from the prospectively collected, multicenter registry of the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC). The 834 female patients with ARM who were enrolled in the registry by January 1, 2020 were included in this study. The relationship of VACTERL association with presence of a gynecologic anomaly was evaluated with Fisher's exact test. The relationship of each VACTERL system with presence of a gynecologic anomaly was assessed in patients with cloaca, rectovestibular fistulas and rectoperineal fistulas. P-values reported were based on a 2-sided alternative and considered significant when less than 0.05. RESULTS: 834 patients with ARM underwent VACTERL screening and gynecologic evaluation with the three most common subtypes being cloaca (n = 215, 25.8%), rectovestibular fistula (n = 191, 22.9%) and rectoperineal fistula (n = 194, 23.3%). A total of 223 (26.7%) patients with ARM had gynecologic anomalies. VACTERL association was seen in 380 (45.6%) of patients with ARM. Gynecologic anomalies were present in 149 (39.1%) vs. 74 (16.3%) of subjects with vs. without VACTERL association (p < 0.001). VACTERL association did not significantly increase the risk of gynecologic anomaly in patients with cloaca and VACTERL (n = 88, 61.5%) vs. cloaca without VACTERL (n = 39, 54.2% p = 0.308). VACTERL association increased the risk of gynecologic anomalies in patients with rectoperineal fistulas (n = 7, 14.9% vs n = 9, 6.1% p = 0.014) and rectovestibular fistulas (n = 19, 31.1% vs. n = 13, 10.0% p<0.001). In patients with ARM who had a VACTERL association, when one of the associated anomalies was renal, there was an even higher risk of having an associated gynecologic anomaly (n = 138, 44.2% vs. n = 85, 16.3% p<0.001). CONCLUSIONS: VACTERL association in patients with rectoperineal and rectovestibular fistulas correlates with an increased risk of gynecologic anomalies. The presence of VACTERL associated findings, especially renal, should prompt a thorough evaluation of the gynecologic system. LEVEL OF EVIDENCE: III. Retrospective comparative study.

Congenital Limb Deficiency: A Case Report.

The complete absence of limbs is a rare occurrence. Though the causes are various, it is hard to elicit most of the time. They are usually diagnosed via anomaly scan but the lack of access to the same can often lead to a term presentation. It is still not uncommon to receive pregnant patients at term to the hospital or in labour as the first antenatal visit. Increasing the feasibility of the scan can help in the early diagnosis and management. Here, we report a rare combination of limb defects that we managed in a district-level hospital and highlight the difficulties in the management and referral of the patients while working in rural areas. Keywords: amelia; antenatal care; congenital limb deformities; fetal ultrasonography.

Hypothesis: Central digit hypoplasia.

Limb deficiencies are a common birth defect. A malformations surveillance program among many newborns, stillborn fetuses, and malformed fetuses in elective terminations can identify a sufficient number of infants with the same set of abnormalities to characterize a specific limb deficiency phenotype. The active malformations surveillance program was carried out among 289,365 births at Brigham and Women's Hospital in Boston over a 41-year period (1972-2012). The research assistants identified the affected infants and fetuses from reading the findings recorded in each newborn's medical record by the examining pediatricians and consultants and by the pathologists in autopsies. One hundred ninety-four newborn infants and fetuses were found to have a limb deficiency either as an isolated abnormality or as one of multiple malformations. We identified three phenotypes of limb deficiency. We present here the seventeen infants and fetuses with "central digit hypoplasia," a term we suggest for this phenotype: hypoplasia of the thumb and fifth finger with nubbins of soft tissue in place of fingers 2, 3, and 4 at the level of the metacarpal-phalangeal joint. Central digit hypoplasia is to be distinguished primarily from the terminal transverse limb defect that ends at the wrist. In symbrachydactyly, the middle and distal phalanges of the fingers and toes are hypoplastic. In addition, central digit hypoplasia should be distinguished from the amniotic band syndrome, the most common and incorrect diagnosis suggested by the pediatricians and the consultants in this survey. The affected infant and her/his parents benefit from more accurate and specific counseling.

Effects of physical impairments on fitness correlates of the white-footed mouse, Peromyscus leucopus.

Physical impairments are widely assumed to reduce the viability of individual animals, but their impacts on individuals within natural populations of vertebrates are rarely quantified. By monitoring wild populations of white-footed mice over 26 years, we assessed whether missing or deformed limbs, tail or eyes influenced the survival, body mass, movement and ectoparasite burden of their bearers. Of the 27 244 individuals monitored, 543 (2%) had visible physical impairments. Persistence times (survival) were similar between mice with and without impairments. Mice with eye and tail impairments had 5% and 6% greater mass, respectively, than unimpaired mice. Mice with tail impairments had larger home ranges than did unimpaired mice. Burdens of black-legged ticks (Ixodes scapularis) were higher among mice with tail and limb impairments while burdens of bot fly larvae (Cuterebra) were higher among mice with cataracts compared to mice without impairments. Our findings do not support the presupposition that physical impairments reduce viability in their bearers and are inconsistent with the devaluation of impaired individuals that pervaded early thinking in evolutionary biology.

Maternal periconceptional folic acid supplements use and fetus risk for limb defects.

BACKGROUND: Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. OBJECTIVE: To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. METHODS: Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face-to-face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. RESULTS: A total of 63 969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10 000 (n = 63 969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10 000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n = 6462, 10.2%), women who took either FAO (n = 26 567, 42.0%) or MMFA (n = 30 259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%-50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. CONCLUSIONS: Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

Accompanied anomalies in anal atresia or tracheo-esophageal fistula: Comparison with or without VACTERL association.

PURPOSE: We evaluated the various accompanied malformations in patients with anal atresia or tracheoesophageal fistula (TEF). Furthermore, we determined the prevalence of VACTERL association and compared the clinical findings with those of patients without VACTERL association. METHODS: We enrolled the patients with anal atresia or TEF with/without esophageal atresia. We collected the patient data pertaining to accompanied vertebral, cardiovascular, renal or limb anomalies, single umbilical artery, maternal diabetes mellitus or drug history, and gene research. RESULTS: A total 155 patients (65 boys and 90 girls) were enrolled with 147 cases of anal atresia, 3 cases of TEF, and 5 cases of anal atresia with TEF. The prevalence of accompanied anomalies was 67.1% in cardiovascular, 27.1% in renal, 9.7% in vertebral, 2.6% in limb anomalies, and 3.9% in single umbilical artery. Thirty-six (23.2%) patients were diagnosed with VACTERL association. The patients with VACTERL association had a significantly higher number of male patients (58.3 vs. 37.0%, p = .033) and single umbilical artery (11.1 vs. 1.7%, p = .026), and had a significantly lower birth weight (2.8 vs. 3.1 kg, p = .033) than the patients without VACTERL association. Genetic studies were performed in 111 patients, and 8 (7.2%) had chromosomal abnormalities-3 in VACTERL and 5 in no VACTERL group. CONCLUSION: We recommend a careful evaluation for VACTERL association in patients with anal atresia or TEF. It is particularly important to screen for a single umbilical artery for features of VACTERL association as well as for other congenital anomalies.

Neurocognitive, adaptive, and psychosocial functioning in individuals with Robinow syndrome.

It has been estimated that 10-15% of people with Robinow syndrome (RS) show delayed development, but no studies have formally assessed developmental domains. The objective of this study is to provide the first description of cognitive, adaptive, and psychological functioning in RS. Thirteen participants (10 males) aged 4-51 years were seen for neuropsychological screening. Eight had autosomal-dominant RS (DVL1, n = 5; WNT5A, n = 3), four had autosomal-recessive RS (NXN, n = 2; ROR2, n = 2), and one had a mutation on an RS candidate gene (GPC4). Participants completed measures of intellectual, fine-motor, adaptive, executive, and psychological functioning. Findings indicated generally average intellectual functioning and low-average visuomotor skills. Adaptive functioning was average in autosomal-recessive RS (RRS) but low average in autosomal-dominant RS (DRS). Parent-report indicated executive dysfunction and attention problems in 4/8 children, 3/4 of whom had a DVL1 variant; adult self-report did not indicate similar difficulties. Learning disabilities were also reported in 4/8 individuals with DRS, 3/4 of whom had a DVL1 variant. Peer problems were reported for a majority of participants, many of whom also reported emotional concerns. Altogether, the findings indicate average neurocognitive functioning in RRS. In contrast, DRS, especially DVL1 pathogenic alleles, may confer specific risk for neurodevelopmental disability.

Risk Factors and Prevalence of Limb Deficiencies Associated With Amniotic Band Sequence: A Population-based Case-control Study.

BACKGROUND: Limb deficiencies associated with amniotic bands comprise a wide range of congenital anomalies. The association of maternal medication and the risk of amniotic band sequence (ABS) has not yet been addressed. METHODS: This nationwide population-based case-control study used national registers on congenital anomalies, births and induced abortions, cross-linked with information on maternal prescription medicine use obtained from the registers on Reimbursed Drug Purchases and Medical Special Reimbursements. All cases with congenital limb deficiency associated with amniotic bands born between 1996 and 2008 were included in the study. Five controls without limb deficiency matched for residency and time of conception were randomly selected from the Medical Birth Register. RESULTS: In total, 106 children with limb deficiency associated with ABS were identified and compared with 530 matched controls. Young maternal age (less than 25 y) increased the risk of limb deficiencies [odds ratio=1.72; 95% confidence interval (CI): 1.06, 2.80]. Primiparity was also associated with increased risk [adjusted odds ratio (aOR)=2.42; 95% CI: 1.52, 3.88]. After adjusting for maternal age, pregestational diabetes, and parity, maternal use of beta-blockers (adjusted OR=24.2; 95% CI: 2.57, 228) and progestogens (adjusted OR=3.79; 95% CI: 1.38, 10.4) during the first trimester of pregnancy significantly increased the risk of limb deficiencies associated with amniotic bands. CONCLUSIONS: Primiparity significantly increased the risk of limb defects associated with amniotic bands. Also, a novel association on increased risk of ABS with maternal use of progestogens or beta-blockers during the first trimester of pregnancy was observed. LEVEL OF EVIDENCE: Level III.

Further defining the clinical and molecular spectrum of acromesomelic dysplasia type maroteaux: a Turkish tertiary center experience.

Acromesomelic dysplasia type Maroteaux (AMDM, OMIM #602875) is an autosomal recessive disorder characterized by severe short stature, shortened middle and distal segments of the limbs, redundant skin of fingers, radial head subluxation or dislocation, large great toes and cranium, and normal intelligence. Only the skeletal system appears to be consistently affected. AMDM is caused by biallelic loss-of-function variants in the natriuretic peptide receptor B (NPRB or NPR2, OMIM #108961) which is involved in endochondral ossification and longitudinal growth of limbs and vertebrae. In this study, we investigated 26 AMDM patients from 22 unrelated families and revealed their genetic etiology in 20 families, via Sanger sequencing or exome sequencing. A total of 22 distinct variants in NPR2 (14 missense, 5 nonsense, 2 intronic, and 1 one-amino acid deletion) were detected, among which 15 were novel. They were in homozygous states in 19 patients and in compound heterozygous states in four patients. Parents with heterozygous NPR2 variants were significantly shorter than the control. Extra-skeletal abnormalities, including global developmental delay/intellectual disability, nephrolithiasis, renal cyst, and oligodontia were noted in the patient cohort. The high parental consanguinity rate might have contributed to these findings, probably associated with other gene variants. This study represents the largest cohort of AMDM from Turkey and regional countries and further expands the molecular and clinical spectrum of AMDM.

Maternal risk associated with the VACTERL association: A case-control study.

BACKGROUND: The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors. METHODS: A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). RESULTS: Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL. CONCLUSION: We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL.

Etiological diagnosis in limb reduction defects and the number of affected limbs: A population-based study in the Northern Netherlands.

Limb reduction defects (LRDs) that affect multiple limbs are considered to be more often heritable, but only few studies have substantiated this. We aimed to investigate if an etiological diagnosis (genetic disorder or clinically recognizable disorder) is more likely to be made when multiple limbs are affected compared to when only one limb is affected. We used data from EUROCAT Northern Netherlands and included 391 fetuses and children with LRDs born in 1981-2017. Cases were classified as having a transverse, longitudinal (preaxial/postaxial/central/mixed), intercalary, or complex LRD of one or more limbs and as having an isolated LRD or multiple congenital anomalies (MCA). We calculated the probability of obtaining an etiological diagnosis in cases with multiple affected limbs versus one affected limb using relative risk (RR) scores and Fisher's exact test. We showed that an etiological diagnosis was made three times more often when an LRD occurred in multiple limbs compared to when it occurred in one limb (RR 2.9, 95% CI 2.2-3.8, p < 0.001). No genetic disorders were found in isolated cases with only one affected limb, whereas a genetic disorder was identified in 16% of MCA cases with one affected limb. A clinically recognizable disorder was found in 47% of MCA cases with one affected limb. Genetic counseling rates were similar. We conclude that reduction defects of multiple limbs are indeed more often heritable. Genetic testing seems less useful in isolated cases with one affected limb, but is warranted in MCA cases with one affected limb.

Patterns of malformation associated with esophageal atresia/tracheoesophageal fistula: A retrospective single center study.

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is one of the most common gastrointestinal birth defects. It can occur in isolation or in association with other birth defects or genetic syndromes. We retrospectively reviewed the EA/TEF cases evaluated at Rady Children's Hospital San Diego (San Diego, CA) between 2007 and 2016. Data were collected for 157 patients. The majority of patients (105, 66.8%) had an associated major malformation present, and 52 patients (33.1%) had isolated EA/TEF. The patients with associated malformations were distributed as follows: 16 patients (10.2%) had a known genetic syndrome (the most common being Trisomy 21 in 11 patients); six patients (3.8%) had a suspected genetic syndrome; one patient had a suspected teratogenic syndrome (diabetic embryopathy); 30 patients had VACTERL association (19.1%); 32 patients had a "partial VACTERL" association (only two VACTERL-type defects without other malformation); nine patients (5.7%) had one additional non-VACTERL-type birth defect, two patients had VACTERL-type defects plus auricular malformations; and nine patients (5.7%) were classified as "unknown syndrome." A classification of the patterns of malformation of patients with congenital EA/TEF is proposed based on reviewing the data of this relatively large and phenotypically diverse patient group.

Congenital limb reduction defects in 1.6 million births in Argentina.

The objectives of this study were to describe the birth prevalence of limb reduction defects (LRD) in Argentina, their clinical features, and to review the literature on this topic. The data source was the National Network of Congenital Anomalies of Argentina, a surveillance system that has been operative since 2009. Data were collected from November 1, 2009 to December 31, 2016. 1,663,610 births and 702 affected patients were registered during this period. The prevalence of LRD was 4.22/10,000 births (CI 95%: 3.93-4.54). In 15,094 stillbirths, prevalence was 30.80/10,000 (CI 95%: 22.31-40.65). Perinatal mortality (stillbirths plus early neonatal deaths) was 24.6%, mostly explained by postnatal deaths. LRD were classified according to different variables, including Gold's anatomic classification. Then, 41.0% of patients had transverse terminal defects and 50.2% had longitudinal defects. We found multiple and syndromic clinical presentation to be associated with both preaxial LRD and lethality. The prevalence of LRD was lower and perinatal mortality was higher in our study compared to that of previously published studies. Because there is heterogeneity in the inclusion and exclusion criteria among publications, a greater effort should be made in order to include similar populations and to use a unified anatomic classification and nomenclature.

Attention difficulties and physical dysfunction common in children with complex congenital malformations: a study of preschool children with VACTERL association.

AIM: Knowledge on the neurodevelopmental and physical function in children with vertebral defects, anorectal malformations, cardiac defects, tracheo-oesophageal fistula, renal and limb malformations (VACTERL) is scarce. We evaluated Swedish preschool children with VACTERL and identified whether they would need extra support in school. METHODS: From 2015 to 2017, we recruited children aged 5-7 with VACTERL association from the paediatric surgical centre at the University Children's Hospital at Uppsala. Neurodevelopmental function was assessed by age-appropriate intelligence and visual and auditory attention tests, and the children's behaviour and attention were observed by an experienced psychologist. Physical function was evaluated through parental interviews and examinations. Data on patient characteristics, including any surgery and anaesthesia, were extracted from medical records. RESULTS: Of the 13 eligible families, 10 agreed to participate. Intelligence was within the normal range for all children, but attention difficulties were found in eight of the children, requiring adjustments at school, and two of these were later diagnosed with attention deficit hyperactivity disorder. All children had physical dysfunctions that affected their daily nutrition, bowel or bladder functions. CONCLUSION: Attention difficulties and physical dysfunction were common in Swedish preschool children aged 5-7 with VACTERL and they would need support and adjustments when they started school.