Factors associated with late gestational age of diagnosis and/or delayed referral of fetuses with major structural malformations: A study in a tertiary care hospital in South India.

OBJECTIVES: To evaluate the factors related to delayed diagnosis or referral of women with major congenital malformations in a tertiary care hospital in South India, with a specific emphasis on the socioeconomic and psychosocial aspects. METHODS: A retrospective analysis was conducted on 107 pregnant women with confirmed fetal anomalies at Jawaharlal Institute of Postgraduate Medical Education and Research. Both qualitative and quantitative data were collected on factors related to the patient, physician, and healthcare system that could have contributed to the delay. RESULTS: In our study of 107 patients, 98.1% had at least one antenatal check-up before 20 weeks. Among them, 75.2% (79/107) were advised to undergo a mid-trimester anomaly scan, and 70.8% (56/79) actually underwent the scan. However, 62.5% (35/56) of those who had the scan performed at the appropriate time had undetected abnormalities. Retrospective analysis showed that 28.5% (10/35) of these anomalies could have been detected as early as 12-14 weeks of gestation. Additionally, 24.3% (26/107) of women were advised to undergo scans at or after 20 weeks and 4.7% (5/107) had anomalies detected during the scan but were unaware about the findings until subsequent visits. Inadequate healthcare professional training, busy schedules, lack of awareness, and communication gaps were identified as potential reasons for delayed diagnosis. Psychosocial factors such as denial, fear, emotional distress, and anxiety also influenced decision-making and contributed to delayed medical care. CONCLUSION: Addressing healthcare provider training, communication between the healthcare professionals and the patients, and psychosocial factors are essential to prevent delays and improve pregnancy management. Future interventions should focus on awareness, providing comprehensive information, and support for parents facing fetal anomalies.

Assessment of Antenatal and Postnatal Prognostic Indicators in the Outcome of Neonatal Congenital Diaphragmatic Hernia: A Prospective Observational Study.

Context: Despite advances in neonatal intensive care, surgical methods, and anesthesia, congenital diaphragmatic hernia (CDH) is still associated with significant mortality. Predicting which babies will have poorer outcomes is essential to identify the high-risk babies and to give targeted care and accurate prognosis to the parents, especially in a resource crunch set-up. Aims: The aim of this study is to evaluate the antenatal and postnatal prognostic factors in neonatal CDH that can be used to predict the outcome. Settings and Design: This was a prospective observational study in a tertiary care center. Subjects and Methods: Neonates presented with CDH within 28 days of life were included in the study. Bilateral disease, recurrent diseases, and babies operated outside were excluded from the study. The data were collected prospectively, and babies were followed until discharge or death. Statistical Analysis Used: Data were expressed in mean with standard deviation or median with range based on normality. All the data were analyzed using the SPSS software version 25. Results: Thirty babies with neonatal CDH were studied. There were three right-sided cases. The male-to-female ratio was 2.3:1, and 93% of babies were antenatally diagnosed. Seventeen out of the 30 babies underwent surgery. Nine (52.9%) underwent laparotomy, and 8 (47%) underwent thoracoscopic repair. Overall mortality was 53.3%, and operative mortality was 17.6%. Demographic characteristics were comparable between expired versus survived babies. The significant predictors of outcome identified were - Persistent pulmonary hypertension (PPHN), mesh repair, high-frequency oscillatory ventilation (HFOV), use of inotropes, 5-min APGAR, ventilator index (VI), and HCO3 levels. Conclusions: We conclude that the prognostic indicators associated with poor prognosis are low 5-min APGAR, high VI, low HCO3 levels in venous blood gas analysis, mesh repair, HFOV, inotropes usage, and PPHN. None of the antenatal factors studied showed any statistical significance. Further prospective studies with a larger sample size are recommended to confirm the findings.

Locating the Level and Extent of Congenital High Airway Obstruction: Fluid in the Airway Tract as Reference Points.

Described here are a series of four cases of congenital high airway obstruction in the fetus. All of the patients presented in the second trimester and all had hydrops fetalis. Three cases had bilateral hyperinflated lungs, midline shift of heart, flattening or inversion of the diaphragm, and fetal ascites. Autopsy was performed in one of these three and showed laryngeal atresia. In one fetus, there was only a unilateral huge enlargement of the lung with mediastinal shift. On autopsy, this fetus had atresia of right main bronchus. All parents had terminated the pregnancy following the prenatal diagnosis. Laryngeal atresia is an extremely rare fetal anomaly with dismal prognosis. It is important to differentiate the condition from other lesions with a more favorable prognosis, such as congenital adenomatoid malformation of the lung. Much research is needed in the future to explore the therapeutic options, including fetoscopic intervention or transplantation of stem cell-derived airways.

The Assisted Reproductive Technology Act 2021- Provisions and Implications.

The desire for parenthood among infertile individuals is often fulfilled by resorting to the ever-evolving Assisted Reproductive Techniques (ART). Since the birth of Durga, India's first baby born using ART in 1981, the lucrative fertility industry has grown exponentially in our country. The Government of India passed the Assisted Reproductive Technology (Regulatory) Act in 2021 to provide regulatory support to these services. The legislation offers clarity on various aspects of ART, including measures to safeguard children born through these procedures. The effective implementation of the ART Act is crucial to ensure that ART services become affordable, ethical, and socially acceptable in India. This article aims to discuss the controversies with ART services and issues that could compromise the wellbeing of children, while highlighting the provisions provided under the Act to address these.

A POLR3B-variant reveals a Pol III transcriptome response dependent on La protein/SSB.

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B:c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B. Genome-edited POLR3B1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E. La protein was increased relative to its abundant pre-tRNA ligands which bind via their U(n)U-3'-termini. Assays for cellular transcription revealed greater deficiencies for tRNA genes bearing terminators comprised of 4Ts than of ≥5Ts. La-knockdown decreased Pol III ncRNA expression unlinked to RNA stability. Consistent with these effects, small-RNAseq showed that POLR3B1625A>G and patient fibroblasts express more tRNA fragments (tRFs) derived from pre-tRNA 3'-trailers (tRF-1) than from mature-tRFs, and higher levels of multiple miRNAs, relative to control cells. The data indicate that decreased levels of Pol III transcripts can lead to functional excess of La protein which reshapes small ncRNA profiles revealing new depth in the Pol III system. Finally, patient cell RNA analysis uncovered a strategy for tRF-1/tRF-3 as POLR3-deficiency biomarkers.

Rubella immunity among pregnant women and the burden of congenital rubella syndrome (CRS) in India, 2022.

BACKGROUND: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. METHODS: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. RESULTS: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. CONCLUSION: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella.

Genetic Studies in Infants with Congenital Nephrotic Syndrome: A Case Series.

Information on the genetic profile of congenital nephrotic syndrome (CNS) from India is scarce. The management of CNS is largely supportive of the setting of developing countries, mainly via the administration of intravenous albumin infusions, angiotensin-converting enzyme inhibitors, and levothyroxine. Inadequate infrastructure and management facilities, including genetic analyses, further hamper the outcome. These infants may progress to end-stage renal disease, and mortality is high in infancy. Here, we report a case series of four infants (aged 14-60 days) with CNS from our center with genetic mutations (including mutations in the NPHS1 and LAMB2 genes) that were not described in previous reports from India. Although responsiveness to enalapril has been documented in anecdotal reports of NPHS1 mutations, our case series of four infants did not exhibit any response to enalapril. Our case series adds to the existing literature regarding the genetic profile of CNS in India.

Prenatal grading of fetal congenital heart disease and its influence on decision making during pregnancy and postnatal period: a prospective study.

BACKGROUND: Congenital heart defects(CHDs) are an important cause of neonatal mortality and morbidity. With advances in diagnosis and treatment, many defects are now amenable to correction. There is a need for individualized approach to prenatally detected lesions to predict the likely prognosis. Assigning them into risk category helps in prenatal counseling, decision making, referrals and formulation of management plan to improve the outcome. OBJECTIVE: To grade the fetal CHDs according to severity and study its usefulness in decision making. METHODS: A prospective study at a tertiary care institute between 2016 and 18, including pregnant women with antenatal diagnosis of fetal CHD. Detailed fetal echocardiography was followed by classification of lesions into four risk categories using modified grading system: (A) extremely high risk; (B) high risk (C) moderate risk (D) low risk. Appropriate counseling was provided to facilitate decision making and further management. The grading was reviewed and revised again postpartum/post-mortem for correlation. RESULTS: Of the total 137 cases, almost half (45.53%) were Category B, while Category D, C and A had 24.1%, 20.4% and 10.2% of cases respectively. The mean gestation age at diagnosis was 26.5 weeks. Termination of pregnancy was done in 21 cases, mostly in Category B (71.4%) and of the 116 continued pregnancies, there were 16 intrauterine deaths. Prenatal and postnatal findings were available in 109 cases and kappa analysis for agreement between antenatal and postnatal grading showed good agreement (0.82). CONCLUSION: Prenatal grading of congenital heart disease is a reliable, structured and simplified tool that can be used for providing counseling and facilitate decision making.

Distal arthrogryposis type 5D in a South Indian family caused by novel deletion in ECEL1 gene.

Distal arthrogryposis (DA) is a heterogeneous group of disorders with congenital, nonprogressive contractures affecting the joints of distal extremities. About 13 distinct subtypes have been defined based on phenotypic features and the different genes known to be causative typically encode for sarcomeric proteins of the contractile apparatus. Although most subtypes are inherited in autosomal dominant manner, distal arthrogryposis type 5D (DA5D) is the only type inherited as an autosomal recessive disorder with a prevalence of <1/1 000 000. We are reporting the phenotype of three members of a family affected by DA5D caused by a novel deletion in the ECEL1 gene. All of them exhibited the distal arthogryposis involving hands and feet, scoliosis, unilateral drooping shoulder, ptosis, central furrow over tip of the tongue and typical facial features.

Prognostic Value of Coronary Artery Calcification Identified by the Semi-quantitative Weston Method in the Emergency Room or Other Hospitalized Patients.

Background: Coronary artery calcification (CAC) may provide insight to the patients' coronary artery disease (CAD) risks and influence early intervention. With increasing use of non-gated CT scans in clinical practice, the visual coronary artery scoring system (Weston Method) could quickly provide clinicians with important information of CAC for patient triage and management. Methods: We retrospectively studied the available CT imaging data and estimated CAC burden using the Weston method in 493 emergency room or other hospitalized patients. The Weston scores were calculated by the sum of the score for each vessel including the left main, left anterior descending, left circumflex artery and right coronary artery (range 0-12). The primary endpoint was a composite of the major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and coronary revascularization. Results: During a median follow-up of 85 months, a total of 25 (5.1%) MACE were recorded and 57 (11.2%) patients died from any causes. Detectable CAC was most common (96%) in the left anterior descending coronary arteries. Multivariable analysis showed that CAC total scores were independent predictors for MACE and all-cause mortality. Receiver operating characteristic analysis showed that CAC total score ≥5 was the optimal cutoff value for predicting MACEs. Conclusions: In the emergency room and hospitalized patients, the semi-quantitation of CAC burden using the Weston score system was related to the long-term cardiovascular outcomes including mortality. Clinicians and radiologists should maximize the value of non-contrast chest CT images by reporting CAC details.

An unusual case of cervico-cutaneous fistula.

A lady presented with 6 months of amenorrhea and cyclical menstruation through an opening in the abdominal wall for the same duration, following septic abortion. Examination and investigations revealed an extraperitoneal Cervicocutaneous fistula, which was excised in toto. She had an uneventful recovery and resumed normal periods.

Prenatal diagnosis of fetal right and left congenital ventricular aneurysms.

AIM: To describe the ultrasonographic appearance of fetal ventricular aneurysm. METHODS: Ultrasound characteristics of two cases of prenatally diagnosed fetal ventricular aneurysm were reviewed. RESULTS: There was one case of left ventricular aneurysm diagnosed by prenatal ultrasound at 38 weeks of gestation. Another case of fetal right ventricular aneurysm was diagnosed prenatally at 36 weeks of gestation. Both the babies expired in the immediate post-natal period. CONCLUSION: Congenital ventricular aneurysm is a rare cardiac malformation characterized by protrusion or out pouching of a portion of the ventricular wall. It is important to differentiate an aneurysm from diverticulum, as the latter has favorable prognosis. The aneurysms are usually large and have broad-based communication with the ventricular cavity in contrast to diverticuli, which are small and connected by a narrow base.

Single Nucleotide Polymorphism-Based Noninvasive Prenatal Testing: Experience in India.

INTRODUCTION: Noninvasive prenatal testing (NIPT) has revolutionized prenatal screening for chromosomal aneuploidies in some countries. Its implementation has been sporadic in developing countries. Given the genetic variation of the people in different countries, we evaluated the performance of the SNP-based NIPT in India . MATERIALS AND METHODS: The Panorama™ NIPT was performed in 516 pregnancies, which had tested intermediate-to-high risk on conventional first and second trimester screening. Results were confirmed either by invasive diagnostic testing or by clinical evaluation after birth. RESULTS: Of 511 samples analyzed, results were obtained in 499 (97.7%). Of these, 480 (98.2%) were low risk and 19 were high risk. A sensitivity of 100% was obtained for detection of trisomies 21, 18, 13 and sex chromosomal abnormalities. The specificity ranged from 99.3 to 100% for abnormalities tested. Taken together, the positive predictive value for trisomies 21, 18, 13 and monosomy X was 85.7%. The average fetal fraction was 8.2%, which is lower than the average observed elsewhere. CONCLUSION: This is the first report of detailed experience with NIPT in India and demonstrates comparable performance in all aspects of testing to the results elsewhere.

Burst abdomen: an unusual complication of silicosis in pregnancy.

We present a case of silicosis in a 37-year-old pregnant woman, a second gravida with previous caesarean section. She was referred to our hospital at 42 weeks of gestation with breathlessness and oligohydramnios. She had worked in a glass and talc powder factory for 11 years and was diagnosed as having silicosis 2 years prior; she was on treatment. Following admission, she was evaluated for dyspnoea and underwent emergency Caesarean section for poor cervical dilation. She developed a burst abdomen on the third postoperative day with loops of gangrenous bowel protruding outside the abdomen. Emergency laparotomy with ileal resection and ileostomy was carried out. She was discharged on day 14 and is on follow-up. To the best of our knowledge, this is the first case of silicosis in pregnancy presenting with an unusual complication.

Takayasu arteritis of subclavian artery in a Caucasian.

Takayasu arteritis, an inflammatory and obliterative disease of medium and large arteries, is classified as a giant cell arteritis. It has a predilection for the aortic arch, its main branches, and coronary and pulmonary arteries. The early symptoms of Takayasu arteritis may be mainly systemic and may resemble polymyalgia rheumatica. The etiology is unknown but autoimmunity has been suggested to play a role. Diagnosis is based on symptoms, physical findings, and imaging, because tissue diagnosis is rarely feasible. Unlike atherosclerotic vascular disease, Takayasu arteritis affects primarily, but not exclusively, young women. Contrary to earlier reports, it is not limited to the women of Japanese origin but is present worldwide. The current report is of a Caucasian woman who presented with nonspecific complaints of upper back pain, weakness, malaise, and fatigue. Her physical examination revealed absent left radial pulse and a blood pressure differential, later confirmed by radiological imaging studies to be due to left subclavian artery stenosis consistent with Takayasu arteritis. The presentation and management of the patient is described, and Takayasu arteritis is succinctly reviewed.

Thoracic cystic lymphangioma (cystic hygroma): a chest pain syndrome--a case report.

Vascular malformations of the mediastinum including mediastinal lymphangioma are exceedingly rare in adults. A resected case of mediastinal cystic lymphangioma (cystic hygroma) that presented with acute onset of retrosternal chest pain is reported in a 45-year-old man. Cystic hygromas are benign cysts frequently discovered incidentally on chest radiograph. Although computed tomography scan provides helpful information about the size, density, and site of the cysts, it cannot establish a precise diagnosis concerning its nature. Complete removal of the cyst is the treatment of choice and allows precise diagnosis on histologic examination. However, surgical excision is sometimes difficult, owing to the size and extension of the cysts, infiltrating mediastinal planes, enveloping great vessels, and displacing mediastinal organs without invasion. The difficulty of completely eradicating certain cysts explains cases of insidious progression with compressive recurrence. The subject is succinctly reviewed.

Cardiac tamponade and superior vena cava syndrome in lung cancer--a case report.

A combination of pericardial effusion with cardiac tamponade and superior vena caval syndrome is an unusual first presentation of carcinoma of lung, although cardiac involvement is often a late finding in widespread malignancy. Clinical identification can be difficult antemortem. Accurate diagnosis and prompt intervention are necessary to prevent adverse outcomes. Decisions regarding treatment must take into account the clinical presentation and echocardiographic findings. Echocardiography-guided pericardiocentesis with catheter drainage and/or pericardial window is the primary treatment strategy of choice for most large or hemodynamically significant effusions. New cardiac symptoms or classic findings of cardiac tamponade should prompt aggressive investigation. We present a case of adenocarcinoma of the lung that initially presented as pericardial effusion with tamponade and superior vena cava syndrome. The patient had all the clinical features of tamponade such as pulsus paradoxus, tachycardia, elevated jugular venous pressure, hypotension, and electrical alternans on surface electrocardiography. The findings were confirmed on echocardiography and computed tomography of chest, both of which allowed for rapid confirmation of the presence of an effusion and compression of the superior vena cava. The existing literature on the subject is succinctly reviewed.

Positional ventricular tachycardia from a fractured mediport catheter with right ventricular migration--a case report.

The totally implantable catheter system has gained popularity as venous access when prolonged treatment is needed. Despite its frequent use, intravascular fracture and embolization of catheter fragments from implantable venous port-catheter systems present a rare but potentially life-threatening complication. Any implanted catheters should therefore be removed after completion of the treatment or the system's integrity should be monitored on a regular basis. This report illustrates such a case, which presented with ventricular tachycardia triggered by changes in body position from a fractured Mediport catheter with cardiac migration. A 34-year-old woman had a venous port catheter (Mediport) implanted into the right subclavian vein for neoadjuvant radio-chemotherapy for Hodgkin's lymphoma. Owing to the patient's difficult venous access the catheter was left in situ after treatment. Three years after insertion of the Mediport she presented with shortness of breath and palpitations when lying in the left lateral position. Physical examination revealed no abnormalities. An electrocardiogram was within normal rhythm. An outpatient Holter monitor revealed multiple episodes of nonsustained and sustained ventricular tachycardia triggered by lying in the left lateral position. A chest radiograph showed a normal location of the port-system, but the distal fragment of the catheter had embolized into the right ventricle. The embolized fragment was extracted with a gooseneck snare technique and the reservoir of the system was removed under local anesthesia without any complications. The patient was free of symptoms at 7 seven months follow-up.