Spectrum Of Congenital Anomalies Research Articles

Persistent Vetal Vasculature-Vitreoretinal Surgery

Persistent fetal vasculature (PFV), previously known as persistent hyperplastic primary vitreous (PHPV), is a spectrum of congenital anomalies caused by complete or partial failure of the fetal hyaloid vasculature to regress. The severity of the disease may vary depending on the affected intraocular structures and anatomical variations. The outcomes of surgery depend on the type, location, extent, and severity of the disease. The aim of this review is to focus on surgical indications and techniques, and the prognosis of PFV in the current literature and our clinical experience.

From diagnosis to postoperative challenges: a comprehensive case report on 2q37 deletion syndrome with CHD.

Chromosomal 2q37 deletion syndrome, marked by developmental delays, distinctive facial features, and a spectrum of congenital anomalies, presents significant challenges in the cardiac management of affected individuals. This paper details the case of an 8-month-old male with 2q37 deletion syndrome, manifesting atrial and ventricular septal defects, patent ductus arteriosus, and right ventricular outflow tract stenosis, leading to a demanding postoperative course. Despite an initially stable post-surgery phase, the onset of junctional ectopic tachycardia necessitated prolonged veno-arterial extracorporeal membrane oxygenation support, highlighting the syndrome's potential for intricate postoperative courses. The complexities encountered in this case, including extended renal replacement therapy and delayed thoracic closure, underscore the syndrome's multisystem impact and the critical need for tailored, multidisciplinary care approaches. This report contributes to the growing body of knowledge on the cardiac implications of 2q37 deletion syndrome, emphasising the importance of individualised surgical strategies and the ongoing exploration of genotype-phenotype correlations in this rare genetic disorder.

Incidence and Spectrum of Congenital Anomalies in Pediatric Populations of Southern Punjab, Pakistan

Background: Congenital anomalies (CAs) remain a significant concern for pediatric health worldwide, affecting millions of newborns. In Southern Punjab, Pakistan, a region characterized by its distinct socio-cultural dynamics, including a high prevalence of consanguineous marriages, the impact of these anomalies presents a unique public health challenge. This study aims to shed light on the incidence and spectrum of CAs within this context, exploring the genetic and environmental factors contributing to their prevalence.
 Objective: The primary objective of this study was to estimate the incidence and types of congenital anomalies among the pediatric population of Southern Punjab, with a particular focus on the relationship between consanguineous marriages and the prevalence of CAs.
 Methods: A cross-sectional study design was utilized, encompassing 406 pregnant women aged 20-42 from Southern Punjab, screened via ultrasound and genetic testing. The study emphasized the categorization of CAs across five main systems: digestive, central nervous, cardiovascular, ear-face-neck, and musculoskeletal. The inclusion of women with a history of cousin marriages provided a comparative analysis to understand the genetic impact on CA incidence.
 Results: Out of 406 newborns, a total of 16 (3.94%) were diagnosed with congenital anomalies. The distribution of CAs was as follows: digestive system (5 cases, 1.23%), central nervous system (3 cases, 0.74%), cardiovascular system (5 cases, 1.23%), anomalies of ear, face, and neck (3 cases, 0.74%), and musculoskeletal system (3 cases, 0.74%). Notably, the prevalence of CAs was higher in children born from cousin marriages (12 cases, 2.95%) compared to those from non-consanguineous unions (4 cases, 0.99%), with a statistically significant p-value of 0.05.
 Conclusion: The study underscores the heightened risk of congenital anomalies associated with consanguineous marriages in Southern Punjab, Pakistan. These findings advocate for enhanced genetic counseling and prenatal screening programs in regions with similar socio-cultural practices to mitigate the risks and impact of CAs.

A Comprehensive Review on Asthma Challenges in Pregnancy: Exploring First Trimester Exacerbations and the Spectrum of Congenital Anomalies.

This comprehensive review delves into the intricate relationship between asthma and pregnancy, specifically focusing on the challenges encountered in the first trimester and the ensuing impact on maternal and fetal health. Examining physiological changes during pregnancy reveals the dynamic interplay influencing respiratory function and immune responses. Key findings underscore the vulnerability to asthma exacerbations in the critical first trimester, emphasizing the potential risks to both maternal and fetal well-being. Maternal and fetal outcomes are discussed, emphasizing the associations between poorly controlled asthma and adverse perinatal outcomes. Implications for clinical practice highlight the importance of preconception care, continuous monitoring, and collaborative efforts between obstetricians and pulmonologists. Patient education emerges as a fundamental aspect to empower pregnant women in managing their condition. The conclusion emphasizes the imperative for comprehensive care, advocating for individualized treatment plans, multidisciplinary collaboration, and public health initiatives. By adopting this holistic approach, healthcare providers can navigate the complexities of asthma during pregnancy, ultimately ensuring the optimal health of both the expectant mother and her developing fetus.

Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model.

Zika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes. Here, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized. Dams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection. Thus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates LZTR1 in Disease Formation.

The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2. The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (NR1H2, GKAP1), four candidate genes with autosomal-recessive biallelic variants (AKR1B10, CLSTN3, NDST4, PLEKHB1) and one candidate gene with suggestive uniparental disomy (SVEP1). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in LZTR1 (c.978_985del, p.Ser327fster6) and in SLC7A4 (c.1087delC, p.Arg363fster68). According to previous studies, our study further implicates LZTR1 in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed.

Low Immune Cross-Reactivity between West Nile Virus and a Zika Virus Vaccine Based on Modified Vaccinia Virus Ankara.

Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain–Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.

Contrast Agent Mimicking Calculi in Entrapped Calyx. A Report of a Case

Urolithiasis is a common condition, and it represents a large number of hospital visits. Under the term infundibulopelvic dysgenesis, many conditions amongst a spectrum of congenital disorders of the pelvicalyceal system are described. Retrograde intrarenal surgery (RIRS) is an effective and safe treatment modality in the management of urinary system stone disease. Fluoroscopic imaging is a cornerstone in endourology. Herein, we present a case where we diagnosed an obstructed calyx during RIRS for renal calculi and operated on it. In this extraordinary case, contrast agent was trapped in the calyx mimicking a renal stone and that was the reason that we discovered the infundibular stenosis. The patient, 24 h after the operation, left the hospital without any complications reported.

Chronic pelvic pain in a patient with Mayer-Rokitansky-Küster-Hauser syndrome: An unusual presentation

Introduction: MRKH syndrome, is a spectrum of congenital anomalies of unknown aetiology characterised by a variable degree of utero-vaginal agenesis in women with normal secondary sexual characteristics and a 46, XX karyotype. Case report: A 16 year old unmarried presented with absence of menses and chronic pelvic pain. MRKH with endometrioma was diagnosed on MRI. Laparoscopic removal of the Mullerian mass with endometriotic cyst was done. The diagnosis was subsequently confirmed on histology. Conclusion: This case highlights the atypical presentation of MRKH and reinforce the Sampsons theory of retrograde menstruation in the development of endometriosis. Patient with chronic pelvic pain and MRKH syndrome should be evaluated for endometriosis.

Urban-rural residence and birth defects prevalence in Texas: a phenome-wide association study.

Some assessments indicate the prevalence of certain birth defects varies by urban-rural status. We evaluated associations between urban-rural residence and a spectrum of birth defects, using a phenome-wide association study approach in Texas, a state with large urban centers and expansive rural areas. Data for birth defects and livebirths during 1999-2015 were obtained from the Texas Birth Defects Registry and the Center for Health Statistics. Maternal residence was classified as urban or rural, and prevalence ratios (PR) and 95% confidence intervals (CI) were calculated for any defect and 140 specific defects by Poisson regression. Overall, birth defects were less frequent in rural compared to urban counties (PR = 0.88, 95% CI: 0.87-0.89). Twelve specific defects were less prevalent in rural counties, including ventricular septal defects (VSDs; PR = 0.76, 95% CI: 0.73-0.79) and hypospadias (PR = 0.86, 95% CI: 0.82-0.89). For some birth defects, including VSDs, there was evidence of decreasing prevalence with decreasing population size. In our large population-based assessment, we demonstrated that several birth defects were less prevalent in rural counties, suggesting that characteristics of urban settings may be relevant to their etiologies, diagnosis, or surveillance. Further research is needed to identify specific exposures underlying these associations. There are few studies of birth defects prevalence in urban versus rural settings. To address this, we investigated a comprehensive range of birth defects, including several rare defects that have not been previously studied, in a large and diverse population. We identified 12 structural birth defects that were less prevalent in rural areas. Findings suggest possible differential exposures among urban and rural women, and/or possible underdiagnosis of certain birth defects in rural areas. Findings highlight the need for further study of geographically referenced risk factors for birth defects, and of the completeness of birth defects ascertainment in rural areas.

Congenital heart disease in Zika virus congenital syndrome: How and when to investigate

The congenital Zika virus syndrome (CZS) presents a wide spectrum of congenital abnormalities, especially neurological alterations, such as microcephaly (1). Recent studies have evaluated congenital heart disease (CHD) as a possible component of the CZS spectrum (2). In the same way as in congenital rubella syndrome (CRS)(1), cardiac malformations might be part of the multiple systemic disorders.The Brazilian Ministry of Health established a protocol that includes pulse oximetry and echocardiographic screening in the investigation of neonates with suspected CZS(1).

O-006 Diagnosis debate – USG vs endoscopy

Abstract text MULLERIAN ANOMAIES – DEBATE USG OR ENDOSCOPY Mullerian duct anomalies are a complex spectrum of congenital anomalies resulting from defective fusion or canalization leading to different uterine anomalies. Early detection and proper diagnosis of uterine anomalies are paramount for proper management. Outflow obstruction defects like transvers septal defects or non canalised functional horn present early with complaint of pain while rest of patients present with amenorrhoea , infertility, repeated first-trimester abortion, fetal intrauterine growth restriction, and obstetric complications.The prevalence of uterine malformations is variable depending on the population studied , 0.4% , 4 % respectively in the general population and in infertile women while a high prevalence between 3 and 38% is reported in patients with repeated spontaneous miscarriages. Imaging plays an important role in diagnosis and treatment planning in mullerian duct anomalies. There are different imaging and endoscopic modalities that can be used for the diagnosis and confirmation of uterine malformations. All modalities are having limitations and one need to select and combine various modalities depending on the clinical presentation of patient and pelvic examination. In younger patients or acute cases, trans abdominal ultrasonography (US) is the preferred method because it is readily available, inexpensive, and rapid and does not use ionizing radiation. However it may not give the complete picture because of poor demarcation especially in fatty patient and owing to complex nature of defects , Field-of-view restrictions with US, patient body habitus, and artefact from bowel gas. Pelvic magnetic resonance imaging (MRI) is an excellent tool in the diagnosis of Mullerian duct anomalies due to high soft tissue resolution. But it is more expensive and less available. 3D ultrasound may be a valid alternative to pelvic MRI as It is less expensive and better tolerated by patients however in doubtful cases of complex nature , hysteroscopy combined with laparoscopy may be considered to confirm the diagnosis. Another advantage of endoscopy is the opportunity to correct the defect in the same sitting in most of the cases. Hysterosalpingography (HSG) and hysteroscopy are considered good modalities to assess the uterine cavity. Hysteroscopy provide the direct visualisation of the defect and considered as gold standard for cavity evaluation in doubtful cases of septate and bicornuate uterus and for simultaneous correction. However outer contour cannot be visualised so one need to use laparoscopy for complete evaluation which is a major drawback. Three-dimensional transvaginal sonography provides image quality like those provided by MRI and is being extensively used for diagnosis of all sorts of mullerian defects. it has got the advantage of realtime imaging which is helpful in distorted pelvic anatomy , visualisation of outer contour is possible ,which is considered very important to differentiate between bicornuate and septate uterus and unicornuate uterus with rudimentary horn. however it may not be possible in all cases to get a definitive diagnosis inspite of using a high end 3D machine specially in presence of artefacts , distorted contour and retroverted uterus. In such cases both modalities including MRI and endoscopy may be required to reach to a definitive diagnosis. It can be concluded that primary imaging tool is still 2d ultrasound but 3D TVS should be included in all suspected anomalies along with complete careful pelvic examination to corroborate the findings of USG. In doubt ful or complex cases, MRI should be performed particularly for cervical and vaginal atresia and septum. endoscopy should be reserved for all doubtful cases for confirmation and for acute cases where a corrective surgery can also be planned to relieve the distress.

Pathogenic germline IKZF1 variant alters hematopoietic gene expression profiles.

IKZF1 encodes Ikaros, a zinc finger–containing transcription factor crucial to the development of the hematopoietic system. Germline pathogenic variants in IKZF1 have been reported in patients with acute lymphocytic leukemia and immunodeficiency syndromes. Diamond–Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by erythroid hypoplasia, associated with a spectrum of congenital anomalies and an elevated risk of certain cancers. DBA is usually caused by heterozygous pathogenic variants in genes that function in ribosomal biogenesis; however, in many cases the genetic etiology is unknown. We identified a germline IKZF1 variant, rs757907717 C > T, in identical twins with DBA-like features and autoimmune gastrointestinal disease. rs757907717 C > T results in a p.R381C amino acid change in the IKZF1 Ik-x isoform (p.R423C on isoform Ik-1), which we show is associated with altered global gene expression and perturbation of transcriptional networks involved in hematopoietic system development. These data suggest that this missense substitution caused a DBA-like syndrome in this family because of alterations in hematopoiesis, including dysregulation of networks essential for normal erythropoiesis and the immune system.

Hemiuterus with functional non-communicating horn in a young female

BackgroundMullerian duct anomalies are a broad spectrum of congenital anomalies of the female genital tract presenting with variable symptoms like infertility, amenorrhoea, dysmenorrhea, pelvic endometriosis, and poor obstetric outcomes. Unicornuate uterus or hemiuterus occurs as a result of abnormal formation or failure of formation of the contralateral part.Case presentationWe present a rare case report of hemiuterus with functional non-communicating horn along with hematometra in a 15-year-old female who presented with severe dysmenorrhoea since her menarche. Pelvic Ultrasonography demonstrated inconclusive findings of a heterogenous lesion in the right pelvic cavity adjacent to the uterus. Further, pelvic MRI revealed a hemiuterus on the left side with a normal endometrial cavity and a well-defined functional non-communicating horn on right side. The diagnosis of European Society of Human Reproduction (ESHRE) Classification U4a uterine anomaly (left hemiuterus with functional non-communicating horn on right side) was established.ConclusionsESHRE Class U4a comprises of hemiuterus with a functional rudimentary horn. This is considered clinically significant as it may lead to further complications, such as hematometra or ectopic pregnancy in the rudimentary horn. Hence, the correct identification of this entity is essential as laparoscopic removal is the current recommended management.

Anatomoclinical correlation and main radiological findings in a patient affected by Arnold Chiari's malformation: a review

Chiari's malformation is within the spectrum of congenital abnormalities of the central nervous system (CNS). It is characterized by a complex deformity of the posterior fossa associated almost always with a malformation of the spine. Chiari malformation is still a subject of little evidence in literature, where new studies on this parameter may trigger influences for researchers in the field. The objectives of this study were to describe the main alterations found in the nervous system in individuals with Chiari malformation. It is a literature review study. The following descriptors were used for the search: Chiari malformation, Posterior Pit and Craniovertebral Junction (together and separately). In the selection criteria, full articles were chosen for the period: 2016 - 2019, in the languages: Portuguese and English. The searches were made in the databases: Scielo, Pubmed and Google academic. The articles were selected first by title, then by abstract, and finally by full reading. Based on the established criteria, 3 articles were selected that contemplate the theme. The literature shows that the most suggestive brain alterations of this pathology are cerebellar abnormalities such as caudal displacement of the bridge, IV ventricle and bulb; medullary torsion; IV ventricle in abnormal shape and hypoplasia of the cerebellum tent and mesencephalic ceiling. It is noticeable that Chiari's malformation can cause alterations that can vary from lighter to more severe. New studies are needed on this subject, as well as solutions to improve the quality of life of patients affected by this syndrome.

Epidemiology of Multiple Congenital Anomalies Before and After Implementation of a Nationwide Prenatal Screening Program in Denmark.

Surveillance of congenital anomalies is important in order to detect negative influences from environment, medication, or lifestyle as early as possible. Since most teratogens are associated with a spectrum of birth defects rather than a single defect, analysis of the epidemiology of multiple congenital anomalies is important to detect an increase due to environmental or medicine exposure. The aim of the study was to describe changes in prevalence, types of anomalies, and outcome of pregnancies for fetuses and infants with multiple congenital anomalies before and after introduction of the new screening program in the County of Funen, Denmark. The study was based on data from the EUROCAT registry of the County of Funen for the period 1990 to 2014 covering 135,057 births. The registry includes information about livebirths, fetal deaths after 20 weeks of gestation and terminations of pregnancy after prenatal diagnosis of fetal anomalies. All cases with two or more major congenital anomalies in different organ systems, where the pattern of anomalies were not recognized as part of a chromosomal or genetic syndrome or a sequence were included in the study. Overall prevalence of multiple congenital anomalies was 19.7 per 10,000 pregnancies. There was no significant change in prevalence over time. The prenatal detection rate increased from 26 to 57% after introduction of the screening program (p < 0.001). Proportion of terminations of pregnancy increased from 11 to 30% of all cases and 1-week survival for livebirths increased from 64 to 94%. There was no change in combinations of involved organ systems. The implementation of the new screening program in 2004 has led to an increased prenatal detection rate of multiple congenital anomalies followed by an increased rate of termination of pregnancy for the most severe cases and an increased 1-week survival for liveborn infants with multiple congenital anomalies.

Prevalence & spectrum of congenital anomalies at a tertiary care centre in north India over 20 years (1998-2017).

Background & objectives:Congenital anomalies lead to significant morbidity and mortality. Systematically published data on the prevalence and spectrum of congenital anomalies from India are scarce. This study was aimed to ascertain the prevalence, spectrum, trend, and outcome of congenital anomalies at a tertiary care centre in north India over two decades.Methods:Electronic records of all live births from January 1998 to December 2017 were retrieved, and the neonates with congenital anomaly were included in this retrospective analysis. International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) was used for uniformity and international comparison. The further sub-categorization was done as per the WHO birth defects surveillance manual. The prevalence of individual as well as overall congenital anomalies was calculated. Run charts were used to analyze the trends.Results:In the two decades studied (1998-2017), there were 86850 live births, of which 1578 [1.82%, 95% confidence interval (CI): 1.73-1.91%] neonates had a major congenital anomaly. The overall prevalence of anomalies was 182 (95% CI: 173-191) per 10,000 live births. Malformation of the circulatory system was the most common (28.0%) followed by musculoskeletal (18.6%) and urinary system (14.3%). Congenital anomaly-related death rate was 6.78 per 1000 live births. No significant trend was observed in the annual prevalence, individual malformations or contribution of congenital anomalies to overall mortality over the two decades.Interpretation & conclusions:Our results showed a high prevalence of congenital anomalies which could be responsible for significant mortality, warranting the need for a national surveillance programme and birth defect services. It is important to have a national database to know the overall burden and spectrum of congenital anomalies in the country.

Differential Diagnosis of Amniotic Band and Intrauterine Synechiae in Second Trimester Pregnancy: Case Report

Amniotic band sequence (ABS) describes highly variable spectrum of congenital anomalies that occur in association with amniotic bands. İntrauterine synechiae is a condition in which scar tissue develops within the uterine cavity. We aim to present a case of ABS and a case of intrauterine synechiae and compare their ultrasonographic findings. Ultrasonography revealed contraction ring in the right groin area of the first fetus but second fetus was healthy. The diagnosis of ABS is based upon the presence of characteristic structural findings on prenatal ultrasound or postnatal physical examination. The diagnosis of intrauterine adhesions is based upon visualization of intrauterine adhesions either directly by hysteroscopy or indirectly by other imaging studies. The floor of the intrauterine adhesions is widely and lateral of the uterine cavity and occurs from four layers while the amniotic band is a thin layer and forms fluctuations in the amniotic fluid. Amniotic bands may cause variable spectrum of congenital anomalies whereas intrauterine adhesions do not increase the probability of fetal anomaly because it is out of the amniotic cavity.

Leveraging a phenome-wide approach to identify novel exposure-birth defect associations: A proof of concept using maternal smoking and a spectrum of birth defects.

There are often questions about the impact of exposures on a range of birth defects, but there are few rigorous approaches for evaluating these associations. Using maternal smoking as an example we applied a phenome-wide association study (PheWAS) approach to evaluate the impact of this exposure on a comprehensive range of birth defects. Cases were obtained from the Texas Birth Defects Registry for the period 1999-2015. A total of 127 birth defects were examined. Maternal smoking at any time during the pregnancy was ascertained from the vital record. Data were randomly divided into discovery (60%) and replication (40%) partitions. Poisson regression models were run in the discovery partition, using a Bonferroni threshold of p < 3.9×10-4 . Birth defects passing that threshold in adjusted models were evaluated in the replication partition using p < 0.05 to determine statistical significance. Four birth defects were positively and significantly associated with maternal smoking in both partitions: cleft palate, anomalies of the pulmonary artery, other specified anomalies of the mouth and pharynx, and congenital hypertrophic pyloric stenosis. Obstructive defects of the renal pelvis and ureter showed consistent negative associations. All five defects exhibited significant dose-response relationships. We demonstrated that a statistically rigorous approach can be applied to birth defects registry data to examine the association between specified exposures and a range of birth defects. While we confirmed previously reported associations, others were not validated, likely due to misclassification in exposure based on vital records.