Pattern Of Malformations Research Articles

First trimester COVID-19 and the risk of major congenital malformations-International Registry of Coronavirus Exposure in Pregnancy.

There is limited information about the effects of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection during the first trimester of pregnancy on the risk of major congenital malformations (MCMs). The International Registry of Coronavirus Exposure in Pregnancy (IRCEP) was designed to estimate the relative risk of adverse perinatal outcomes among women with Coronavirus Disease 2019 (COVID‐19) at specific times during gestation. Adult women were eligible to enroll if they had a SARS‐CoV‐2 test, regardless of the results, or clinically confirmed COVID‐19 during pregnancy. Self‐administered questionnaires collected data on SARS‐CoV‐2 infection, pregnancy outcomes (including detailed questions on MCMs), and potential confounders. The analysis of MCMs includes women with either a positive SARS‐CoV‐2 PCR test or a clinical diagnosis of COVID‐19 during the first trimester (exposed group) or a negative SARS‐CoV‐2 test (reference) that enrolled while pregnant. Sensitivity analyses were restricted to participants who enrolled before the availability of informative prenatal screening tests and extended to those enrolled after end of pregnancy. Generalized linear models were used to estimate relative risks (RR) and 95% confidence intervals (CI). Of 17,163 participants enrolled between June 2020 and July 2021, 1727 had a SARS‐CoV‐2 infection during the first trimester, of whom 1,675 enrolled during pregnancy. Of 10,235 controls with a negative test during pregnancy, 4,172 enrolled during pregnancy. Restriction to participants with complete follow‐up reduced the sample size to 92 exposed and 292 unexposed reference pregnancies. MCMs were reported in 3 (3.3%) exposed and 8 (2.7%) unexposed (RR 1.2; 95% CI 0.32–4.2) newborns. The RR was 2.5 (95%CI 0.23–27) among those enrolled before prenatal screening, and 2.2 (95%CI 0.89–5.3) in the overall study population including those enrolled post‐pregnancy. No specific pattern of malformations was observed. Although results are compatible with no major teratogenic effects associated with maternal SARS‐CoV‐2 infection, RR estimates were imprecise and larger studies are warranted.

Major Congenital Malformations of Gastrointestinal Tract Among Neonates Presenting to Tertiary Care

Background: Major congenital malformations of gastrointestinal tract (CMGIT), are usually manifested in early neonatal period by signs of intestinal obstruction and may be life threatening. A broad spectrum of Gastrointestinal Tract (GIT) anomalies can be seen including both upper and lower GIT. As compared to other congenital anomalies, GIT anomalies are not well studied and till now very few studies have reported prevalence and pattern of GIT malformations. Objective: To determine different type of common gastrointestinal anomalies among neonates presenting at tertiary care hospital. Methods: This descriptive cross sectional study was done at National Institute of Child Health (NICH) Karachi over period of 6 months, from 1-8-17 to 31-1-18. All neonates presenting to emergency department and got hospitalized with CMGIT were enrolled. Results: There were 35 neonates enrolled with CMGIT. Out of these 16(45.7%) were male and 19(54.3%) were females. Mean age 9.4+3.82 (range 1-20) days. Mean weight was 2.5±0.98 (range 0.5-4.5) kg. Mean duration of symptoms was 5.8+1.72 (range 1-9) days. Among the CMGIT, 12 (34.3%) cases were of Anorectal malformation, persistent Vitelline duct was found in 6 (17.1%), Intestinal atresia in 4(11.4%), Intestinal stenosis in 5(14.3%), Hirshsprung disease in 4(11.4%) and Exomphalos in 4 (11.4%). Conclusion: Anorectal malformations were most common anomaly followed by persistent vitelline duct. Antenatal follow up and anomaly scan of all neonates should be done. Keywords: Gastrointestinal anomaly, Neonates, congenital anomaly.

Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes.

Variants in RAC3, encoding a small GTPase RAC3 which is critical for the regulation of actin cytoskeleton and intracellular signal transduction, are associated with a rare neurodevelopmental disorder with structural brain anomalies and facial dysmorphism.We investigated a cohort of 10 unrelated participants presenting with global psychomotor delay, hypotonia, behavioural disturbances, stereotyped movements, dysmorphic features, seizures and musculoskeletal abnormalities. MRI of brain revealed a complex pattern of variable brain malformations, including callosal abnormalities, white matter thinning, grey matter heterotopia, polymicrogyria/dysgyria, brainstem anomalies and cerebellar dysplasia. These patients harboured eight distinct de novo RAC3 variants, including six novel variants (NM_005052.3): c.34G > C p.G12R, c.179G > A p.G60D, c.186_188delGGA p.E62del, c.187G > A p.D63N, c.191A > G p.Y64C and c.348G > C p.K116N. We then examined the pathophysiological significance of these novel and previously reported pathogenic variants p.P29L, p.P34R, p.A59G, p.Q61L and p.E62K. In vitro analyses revealed that all tested RAC3 variants were biochemically and biologically active to variable extent, and exhibited a spectrum of different affinities to downstream effectors including p21-activated kinase 1. We then focused on the four variants p.Q61L, p.E62del, p.D63N and p.Y64C in the Switch II region, which is essential for the biochemical activity of small GTPases and also a variation hot spot common to other Rho family genes, RAC1 and CDC42. Acute expression of the four variants in embryonic mouse brain using in utero electroporation caused defects in cortical neuron morphology and migration ending up with cluster formation during corticogenesis. Notably, defective migration by p.E62del, p.D63N and p.Y64C were rescued by a dominant negative version of p21-activated kinase 1.Our results indicate that RAC3 variants result in morphological and functional defects in cortical neurons during brain development through variant-specific mechanisms, eventually leading to heterogeneous neurodevelopmental phenotypes.

Pattern of congenital malformations in new-borns: a hospital based retrospective study

Background: Congenital malformation in new-borns is a major public health problem. Identification of the pattern of congenital malformations and hence control of birth defects is an urgent need.Methods: This retrospective study was carried out in neonatal care unit (NICU) of GMC and RH Patiala, Punjab. All the deliveries conducted from January 2020 to December 2020 were included in the study. All the new born babies were thoroughly examined for the presence of congenital malformations. Detailed maternal history was recorded so as to evaluate association of various maternal risk factors with the congenital malformations. Collected data was analyzed on statistical package for the social sciences (SPSS) software, a p value of less than 0.05 was considered significant.Results: A total of 3962 babies were delivered at GMC and Rajindra Hospital, Patiala during the study period. Out of this, 91 (2.29%) new-borns were identified with congenital malformations. The most common system involved was musculoskeletal 40 (43.9%) followed by central nervous system 24 (26.4%). Among maternal and fetal risk factors; parental consanguinity, maternal under nutrition/obesity, positive history of a congenital anomaly (CA) in the family, and still birth/intrauterine deaths and ambiguous sex of the newborn baby were significantly associated with higher frequency of CAs (p<0.05).Conclusions: Congenital malformations in new-borns becoming the emerging cause of neonatal morbidity and mortality after neonatal infections. Institution of preventive measures with more focus on young mother’s nutrition, provision of health education and early diagnosis of congenital malformations during antenatal period can help to curb the burden of this problem.

A RETROSPECTIVE ANALYSIS OF THE PATTERN OF SURGICAL CONGENITAL MALFORMATIONS IN NORTH EASTERN INDIA

Background: Congenital anomalies (CAs) originate during intrauterine life and interfere with the body functions. CAs are important causes of childhood mortality, chronic illness, and disability. Aim: The study aimed to understand the pattern of surgical congenital malformations in paediatric patients of Tomo Riba Institute of Health and Medical Sciences (TRIHMS) hospital and other nearby hospitals for twelve consecutive years (2007–2019). Methods: This is a retrospective study of 1459 patients (age range 0-14 years) operated at TRIHMS and nearby hospitals of Naharlagun. We collected the data from Operation theatre registers and personal records of operating surgeons from the year 2007 to 2019. Results: The study revealed that congenital anomalies of the gastrointestinal (48.8%), genitourinary system (45.4%), and musculoskeletal system (1.9%) were the most common types of CAs. Males were more affected with CAs than females (73.8% versus 26.2%). Conclusion:Congenital malformations of the gastro-intestinal and genitourinary systems were the most common types of CAs in the hospitals. To prevent CAs, there is a need to restrict the prescription of medications that may have a teratogenic effect.

Congenital malformations: Prevalence and characteristics of newborns admitted into Federal Medical Center, Asaba.

BackgroundCongenital malformations account for a significant cause of perinatal mortality and morbidity. Understanding the burden and pattern of congenital malformation is key in monitoring the trend and improving the health care of neonates especially those in low‐income countries.ObjectiveThis was a prospective cross‐sectional study to determine the prevalence and characteristics of congenital malformations among neonates admitted to the neonatal unit.MethodAll newborns with congenital malformation admitted into the neonatal unit of Federal Medical Center, Asaba whose parents gave consent were recruited for the study for a 1‐year period from January 2020 to December 2020. Appropriately indicated laboratory and radio‐diagnostic investigations were done to confirm internal anomalies. Data were collected using a structured questionnaire and analyzed with a statistical package for social sciences version 26.0.ResultsThe total admission for the period was 752 with 46 of the neonates (6.1%) having congenital malformation. The predominant system affected was the cardiovascular system (57%), central nervous system (33%), and digestive system (30%). Atrioventricular septal defect (31%) and patent ductus arteriosus (31%) were the commonest types of cardiovascular malformation. A significant number of newborns with congenital anomalies died (43.5%).ConclusionCongenital malformation was seen among one in 18 neonates affecting mostly the cardiovascular and central nervous system. A high index of suspicion, early complete physical examination, and radio‐diagnostic investigations are relevant for the complete evaluation of CM in neonates. Advanced maternal age was associated with the presence of multiple organ anomalies.

Pattern and Prevalence of Congenital Malformation and Genetic Disorders among Offspring of Consanguineous Parents in Quetta

This cross-sectional study was carried out to examine the pattern and prevalence of congenital malformation/ genetic disorders among the offspring of consanguineous marriages in Quetta, Pakistan. A survey was conducted among 105 married couples from different areas of Quetta city. 89 out of 105 consanguineous couples were related as first cousins, followed by second cousin (n=16) and third cousin (n=6) couples. Consanguineous marriages were common among women who were illiterate (43.8%) and unemployed (87.6%). Highest number of child mortality (61.9%) and abnormalities (32.1%) were observed among the children of first cousin marriages. The most common congenital malformation /genetic disorders were mental retardation (24.13%), followed by diabetes (10.3%), deafness (6.8%) and thalassemia (6.8%). Among all the inter-related marriages, first cousin marriages are at highest risk to have babies with congenital anomalies.

Developmental Disruptions of the Human Stapes.

To evaluate and classify developmental malformations of the human stapes. Twenty-five temporal bone specimens from 18 patients with congenital stapes malformations were identified in the Mass Eye and Ear temporal bone collection. Serial sections stained with hematoxylin and eosin were examined by light microscopy and the morphology of the stapes was compared to age-matched controls. Each case of stapes malformation could be classified into one of four malformation types based on our current understanding of the embryologic origin of the subunits of the stapes and timing of development. Twenty-seven percent of stapes malformations had a Type I morphology characterized by a hypoplastic or absent inner footplate and hypoplastic to absent mesoderm footplate or oval window. The crura and capitulum may be absent, monopodal or dysmorphic. Eleven percent expressed a Type II malformation with dysmorphic or monopodal capitulum and crura and a fixed footplate. Twenty-seven percent were of Type III with a dysmorphic or monopodal capitulum and or crura. The footplate, and thereby oval window is present and without fixation. The most common malformation, Type IV, was isolated footplate fixation observed in 33% of cases. Malformations of the human stapes follow consistent patterns of early or late disruptions of the stapes subunits of mesodermal and/or neural crest origin. While the molecular events, including temporal coordination, that lead to a normally formed stapes are not yet fully understood, the observed patterns of human stapes malformation can be consistently classified into one of four patterns of developmental disruption.

Nematicidal Activity of Lactic Acid Bacteria against Root-Knot Nematodes

Root-knot nematodes are economically important obligate parasites of plant root that parasitize more than 3000 species of plant. Lactic Acid Bacteria (LAB) are well known as strong producers for wide range of organic acids that have been suggested recently to possess a remarkable lethal effect on root-knot nematodes. In the present ‘study’ 37 LAB strains were isolated from soil and agricultural wastes by using MRS medium and screened for their nematicidal activity under lab conditions. Four bacterial isolates, recorded lethal effect on second stage juveniles by more than 94%, were selected and identified by molecular method. Further, the nematicidal activity at two concentrations (i.e 50 and 10%) of the most promising ten LAB cultures was screened. The nematicidal activity of LAB was positively correlated to the concentration of their suspension cultures.2S4 (Pediococcus pentosaceus MW558270), 2S5 (Pediococcus pentosaceus MW558883), 3S1 (Pediococcus pentosaceusMW558885) and 1A3 (Pediococcus pentosaceus MW558152) isolates showed significant mortality effect by 88.42, 87.37, 81.05 and 85.96%at the low concentration (10%), respectively. In order to confirm the relationship between organic acid production by LAB and their nematicidal activity, an artificial succinic acid, lactic acid, malic acid, acetic acid, and their mixtures were tested at concentration of 1% for their ability to inhibit juvenilesvitality. The mixture of acids induced the maximum mortality effect by 100% followed by lactic acid which recorded 99.66% mortality effect. The microscopic studies and the malformation pattern of the juveniles indicating that the nematicidal activity of LAB may be derived mainly from their natural organic acids mainly lactic acid.

Spectrum of Congenital Malformations and Associated Factors: A Cross-sectional Study from Eastern India

Introduction: Congenital malformations are important contributors for neonatal and infant mortality after prematurity, intrapartum complications and infections. Aim: To find out the prevalence and pattern of congenital malformations among the live born neonates in study area as well as to identify the associated risk factors. Materials and Methods: This descriptive hospital based cross- sectional study was carried out in 305 cases at Midnapore Medical College, Medinipur, West Bengal, from July 2016 to June 2017. All live inborn neonates were assessed for the presence of any malformation(s). The still born or out born babies were excluded. Congenital malformations were diagnosed by clinical examination as well as imaging studies. Data regarding risk factors were collected from the history and the case records. Chi-square test was done to find out the significance of the risk factors. Results: During the study period, there were 14240 live births, out of which 305 cases of congenital malformations were noted. Prevalence of congenital malformations was 214.1 per 10,000 live births or 2.14%. Out of 305 cases, 165 (54.10%) were males, 137 (44.92%) were females, and 3 (0.98%) had ambiguous genitalia. Prevalence of malformations was not significantly different between primi and multipara mothers, and for the different socio-economic backgrounds. A higher prevalence of congenital malformations in mothers above 30 years, consanguinity, low birth weight and prematurity were observed. History of abortion and still birth were associated with higher prevalence. Polyhydramnios, pregnancy induced hypertension and previous abortion and still birth were also associated with higher prevalence of malformations. Musculoskeletal system was majorly involved in 92 (30.16%) cases, followed by central nervous system 48 (15.74%). Conclusion: Prevalence of congenital malformations was found to be 214.1 per 10,000 live births or 2.14%. Maternal age >30, consanguinity, prematurity and low birth weight were associated with increased prevalence of congenital malformations. Musculoskeletal system was the most commonly involved system.

Transcriptome analysis of lncRNA expression patterns in human congenital lung malformations

ObjectivesTo explore the long non-coding RNA (lncRNA) expression pattern of congenital lung malformations on a genome-wide scale and investigate their potential biological function in four subtypes of congenital lung malformations.MethodsWe obtained both lesions and normal lung control tissues from the patients diagnosed with CPAM-I, CPAM-II, ILS, and ILS-CPAM, and underwent lobectomy (i.e., surgical removal of the whole lobe which contains the localized lesion as well as normal lung tissue). Then, we performed lncRNA transcriptome profiling in these tissues by RNA sequencing (RNA-seq). A comprehensive bioinformatics analysis was conducted to characterize the expression profiles and relevant biological functions and for multiple comparisons of lncRNA expression in the different subtypes of congenital lung malformation tissues. Furthermore, the lncRNA-mRNA co-expression network was constructed, and dysregulated mRNAs were functionally analyzed. Finally, gene set enrichment analysis (GSEA) was used to predict the potential molecular mechanism of the identified lncRNAs.ResultsA total of 5921 lncRNA transcripts were identified between congenital lung malformations tissues and normal lung control tissues. Compared with normal lung control, 481of these expressed lncRNAs were upregulated and 142 were downregulated in CPAM-I, 91 were upregulated and 14 were downregulated in CPAM-II, 39 were upregulated and 38 were downregulated in ILS, and 201 were upregulated and 38 were downregulated in ILS-CPAM. Unsupervised clustering and principal component analysis of the expressed lncRNAs visualized the differences between normal lung control and different subtypes of congenital lung malformations samples. We also confirmed significant differences in the composition of differentially expressed genes (DEGs) and the differentially expressed lncRNAs (DE lncRNAs) between CPAM-I and other subtypes of congenital lung malformations, as well as in normal lung control tissues, and observed enrichment of DEGs in the regulation of the immune system, cell projection organization, and inflammatory pathways. Finally, we identified the lncRNA FLJ26850 might be related to congenital lung malformations via ZNF473.ConclusionsSignificant differences in lncRNAs expression patterns were observed between different subtypes of congenital lung malformations and normal control. The lncRNA FLJ26850 might be related to congenital lung malformations via ZNF473.

Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern.

Background/AimsIntrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated.MethodsCases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancer-related genes.ResultsFrom a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR2 and PTPRT were most frequently mutated (three cases each) including an FGFR2-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found.ConclusionsiCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR2 and ARID1A variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

Research progress on the etiology and pathogenesis of spina bifida

To review the research progress on etiology and pathogenesis of spina bifida. By consulting relevant domestic and foreign research literature on spina bifida, the classification, epidemic trend, pathogenesis, etiology, prevention and treatment of it were analyzed and summarized. Spina bifida, a common phenotype of neural tube defects, is classified based on the degree and pattern of malformation associated with neuroectodermal involvement and is due to the disturbance of neural tube closure 28 days before embryonic development. The prevalence of spina bifida varies greatly among different ethnic groups and regions, and its etiology is complex. Currently, some spina bifida patients can be prevented by folic acid supplements, and with the improvement of treatment technology, the short-term and long-term survival rate of children with spina bifida has improved. The research on the pathogenesis of spina bifida will be based on the refined individual information on exposure, genetics, and complex phenotype, and will provide a theoretical basis for improving prevention and treatment strategies through multidisciplinary cooperation.

Vascular malformations of the female and male genitalia: type and distribution patterns revealed by magnetic resonance imaging

Vascular malformations of the genitalia often go undetected in clinical examination. These vascular malformations can cause a variety of clinical symptoms such as swelling, pain and bleeding. To characterize the distribution patterns of genital vascular malformations using magnetic resonance imaging (MRI) and to correlate these patterns with clinical findings in order to guide diagnostic decisions. A retrospective analysis of MRIs of the pelvis and legs in 370 patients with vascular malformation was performed to determine the involvement of the internal and external genitalia. In 71 patients (19%), genital involvement could be identified by MRI. Of these, 11.3% (8 of 71) presented with internal involvement, 36.6% (26 of 71) with external involvement and 52.1% (37 of 71) with both internal and external involvement. Over half (57.1%) of the 49 patients with visible external genital signs detected during a clinical examination had additional internal genital involvement. Genital involvement is a common finding in patients with vascular malformation of the legs and/or pelvis. Based on our data, we recommend MRI of the legs and pelvic region in patients with externally visible signs of a vascular malformation of the external genitalia in order to exclude additional internal involvement.

Head and Neck Lymphatic Malformation Management Algorithm: An Experience from a Tertiary Centre in Tanzania

Background: Lymphatic malformations are localized areas of malformed lymphatic system that can either be congenital or acquired which commonly occur in the head and neck region. Several treatment options for lymphatic malformations have been proposed, despite this, there is no consensus as to optimal management.
 Objective: To determine the pattern and management of head and neck lymphatic malformations in a tertiary health facility in Tanzania.
 Material and Methods: This was a one-year crosssectional study that involved patients with head and neck lymphatic malformations treated in Muhimbili National Hospital. A structured questionnaire was used to collect information including age and sex ofthe patient, chief complaint and, duration, size and site of the lesion. The treatment modalities were surgery and/or intralesional bleomycin injection (IL-Bleo) using a locally developed algorithm. A standard dose of bleomycin was 0.3 to 0.6 mg/kg per injection not exceeding 15 units per cycle with a maximum of 6 cycles.
 Results: a total of 33 patients were included in the study. Males were 21 (63.6%) and the male to female ratio was 1.8:1. The age of patients ranged from 5 months to 28 years with a median age of 6 years. In 29 (87.9%) patients, the lesions were evident during birth. The median area covered by the lesion in 2 patients was 12.00 cm . Nine (27.3%) patients were managed by surgery alone, while majority (24, 72.7%) were given intralesional bleomycin (ILBleo), of whom majority (20, 83.3%) required surgical intervention subsequently. The overall outcome of management of patients was considered successful in 87% of patients.
 Conclusion: Head and neck lymphatic malformations are more common in males. Most of the lymphangiomas are of congenital type. Combining IL-Bleo and surgery an effective way of managing head and neck lymphatic malformations.

Patterns of spinal cord malformation in cloacal exstrophy.

The objective of this study was to assess the prevalence and spectrum of spinal dysraphism in a cohort of children with cloacal exstrophy (CEX) using MRI. Children with CEX presenting between 1999 and 2019 with baseline spinal MRI were included. The images were reviewed in consensus to assess the type of dysraphism. The dysraphisms were initially reviewed and described based on their descriptive anatomy, and then classified according to anomalies of gastrulation, primary neurulation, or secondary neurulation. Thirty-four children were included. Thirty-three of these children had closed spinal dysraphism, and 1 had a normal spine. Of the 33 cases of closed spinal dysraphism, the conus and/or filum terminale were involved in all cases. The most common malformations were spinal lipoma (n = 20) and terminal myelocystocele (n = 11). The lipomas were heterogeneous: 4 dorsal, 9 transitional, 4 chaotic, and 3 terminal. A large subgroup (10/20, 50%) within the lipomas had an unusual morphology of noncontiguous double lipomas, the proximal fat related to the conus and the distal fat within the filum. These were difficult to characterize using existing classifications. In 2 cases, only a thickened filum was noted. The majority of these malformations were compatible with a disorder of secondary neurulation. Complex spinal dysraphisms are consistently associated with CEX. The unusual dysraphism patterns found in this group of patients highlight the limitations of current embryological classifications. Given the propensity for neurological deterioration in this group of patients, spinal MRI should be routinely performed. The type and distribution of malformations seen have implications for the wider understanding of the pathogenesis and classification of lumbosacral lipomas.

Zonisamide safety in pregnancy: Data from the UK and Ireland epilepsy and pregnancy register

BackgroundAnimal data suggest teratogenic effects with zonisamide use and risk of pregnancy losses. Human data following zonisamide exposure are presently limited, but suggest low risk of malformation with elevated risk of low birth weight. ObjectiveTo calculate the major congenital malformation (MCM) rate of zonisamide in human pregnancy and assess for a signal of any specific malformation pattern and associations with birth weight. Methods and materialsData were obtained from the UK and Ireland Epilepsy and Pregnancy register (UKIEPR) which is an observational, registration, and follow up study from December 1996 to July 2020. Eligibility criteria were use of zonisamide and to have been referred to the UKIEPR before the outcome of the pregnancy was known. Primary outcome was evidence of MCM. ResultsFrom December 1996 through July 2020 there were 112 cases of first trimester exposure to zonisamide, including 26 monotherapy cases. There were 3 MCM for monotherapy cases (MCM rate 13.0% (95% confidence interval 4.5–32.1)), and 5 MCM for polytherapy cases (MCM rate 6.9% (95% confidence interval 3.0–15.2)). While the median birth weight was on 71st and 44th centile for monotherapy and polytherapy cases respectively, there was a high rate of infants born small for gestational age (21% for both). ConclusionThese data raise concerns about a signal for potential teratogenicity with zonisamide in human pregnancy. Given the low numbers reported, further data will be required to adequately counsel women who use zonisamide in pregnancy.

First Molars in Permanent Dentition and their Malformations in Various Pathologies: A Review.

Permanent maxillary and mandibular first molars are the first permanent teeth to erupt into the oral cavity along with the mandibular incisors. It serves as an excellent record of maternal and fetal health, reflecting the prenatal, perinatal, and postnatal health and diseases. This review focuses on the molar morphogenesis, molar malformations, their etiopathogenesis, and pathologies causing specific pattern of molar malformations.

POS0022 PHARMACOVIGILANCE PREGNANCY DATA IN A LARGE POPULATION OF PATIENTS WITH CHRONIC INFLAMMATORY DISEASE EXPOSED TO CERTOLIZUMAB PEGOL: PREGNANCY OUTCOMES AND CONFOUNDERS

Background:Chronic inflammatory diseases (CID) in women of reproductive age are increasingly being treated with tumour necrosis factor inhibitors (TNFi), in line with recent guidelines.1 However, data on TNFi-exposed pregnancy outcomes are still limited. Certolizumab pegol (CZP), a PEGylated, Fc-free TNFi, has no/minimal placental transfer from mother to infant during the third trimester.2Objectives:To assess pregnancy outcomes from the UCB Pharmacovigilance safety database from over 1,300 prospectively reported pregnancies with maternal CZP exposure.Methods:Details of CZP-exposed pregnancies from the UCB Pharmacovigilance safety database were reviewed up to November 1, 2020. Analysis was limited to prospectively reported cases with known pregnancy outcomes to avoid potential reporting bias. Confounders (specific CID, non-biologic medications and maternal infection) were evaluated using a multivariate stepwise regression model; results from the confounders analysis are reported as odds ratios (OR) with 95% confidence intervals (CI). Patients with missing information about presence or absence of confounders were excluded from the model.Results:1,392 prospective pregnancies (1,425 fetuses) with maternal CZP exposure and known outcomes were reported (Figure 1). Mean (SD) maternal age was 31.9 (5.1) years. Of these, 1,021/1,392 (73.3%) pregnancies had at least first-trimester CZP exposure and 547/1,392 (39.3%) were exposed during all trimesters. Overall, there were 1,259/1,425 (88.4%) live births, 150/1,425 (10.5%) abortions (miscarriages and terminations), 11/1,425 (0.8%) stillbirths, and 5/1,425 (0.4%) ectopic pregnancies. Congenital malformations were reported in 35/1,425 fetuses (2.5%) and in 30/1,259 live-born infants (2.4%); 26 (2.1%) congenital malformations were major according to the Metropolitan Atlanta Congenital Defects Program criteria. There was no pattern of specific congenital malformations. Preterm births occurred in 124/1,259 (9.8%) live births, and 101/1,259 (8.0%) of infants had low birth weight (<2.5 kg). In the confounders analysis, reported corticosteroid use was independently associated with increased odds of preterm birth (OR [95% CI]: 2.1 [1.3–3.4]; p<0.005) and low birth weight (OR [95% CI]: 1.7 [1.0–2.9]; p<0.05), but decreased odds of abortion (OR [95% CI]: 0.5 [0.3–0.9]; p<0.05). Reported NSAID use was associated with increased odds of abortion (OR [95% CI]: 2.2 [1.2–4.0]; p<0.05), as was methotrexate/leflunomide use (OR [95% CI]: 3.2 [1.7–6.2]; p<0.0005). Maternal infections were associated with increased odds of preterm birth (OR [95% CI]: 1.9 (1.1–3.5; p<0.05). Finally, there was an association between a diagnosis of Crohn’s disease and odds of abortion (OR [95% CI]: 2.5 [1.5–4.1]; p=0.0005), and between rheumatoid arthritis and low birth weight (OR [95% CI]: 1.9 [1.1–3.3]; p<0.05).Conclusion:This prospective analysis, including more than 1,000 pregnancies with CZP exposure in at least the first trimester, represents one of the largest cohorts of pregnancies with known outcomes in patients with CID. Our data confirm the impact of specific CID, concomitant drugs or comorbidities on pregnancy outcomes. In particular, additional use of corticosteroids was highlighted as a risk factor for preterm birth and low birth weight in our cohort of CZP-treated patients. No increase in adverse pregnancy outcomes or specific congenital malformations was observed in CZP-exposed pregnancies, compared to the general population,3,4 which offers further reassurance for women of childbearing age considering CZP treatment.

Fifty years of recognizable patterns of human malformation: Insights and opportunities.

Now in its 7th edition, Smith's Recognizable Patterns of Human Malformation was first published in 1970. This 1st edition comprised 135 "dysmorphic syndromes of multiple primary defects" and 12 "single syndromic malformations resulting in secondary defects." Of the former, other than a few chromosomal and environmental disorders, most were heritable conditions of then unknown etiology. In 2021, the majority of these conditions are now "solved," a notable exception is Hallermann-Streiff syndrome. The "solved" conditions were typically clinically delineated decades prior to understanding the underlying etiology, which rarely required recent technologies such as exome sequencing (ES) to elucidate. The 7th edition includes nearly 300 syndromes, sequences, and associations. An increasing number of conditions first appearing in the latest editions are sporadic, with many solved using either array CGH or ES. We have reviewed all syndromes that have appeared in "Smith's" with a focus on inheritance, heterogeneity, and year and method of etiologic discovery. Several themes emerge. Genetic heterogeneity and pleiotropy of genes are frequent. Several of the currently "unresolved" syndromes are clinically diverse such as Dubowitz syndrome. Multiple recurrent constellations of embryonic malformations, with VACTERL association as a paradigm, are increasingly likely to have a shared pathogenesis requiring further study.