Predictors of Preterm Neonatal Mortality in India and Pakistan: A Secondary Analysis of Data from PURPOSe Study.

To create a prediction model for preterm neonatal mortality. A secondary analysis was conducted using data from a prospective cohort study, the Project to Understand and Research Preterm Pregnancy Outcome South Asia. The Cox proportional hazard model was used and adjusted hazard ratios (AHR) with 95% confidence intervals (95% CI) were reported.

Infancy-onset diabetes caused by de-regulated AMPylation of the human endoplasmic reticulum chaperone BiP.

Dysfunction of the endoplasmic reticulum (ER) in insulin-producing beta cells results in cell loss and diabetes mellitus. Here we report on five individuals from three different consanguineous families with infancy-onset diabetes mellitus and severe neurodevelopmental delay caused by a homozygous p.(Arg371Ser) mutation in FICD.

Identifying the current status and future needs of clinical, educational, and laboratory genetics services in Pakistan: a web-based panel discussion.

While the prevalence of genetic disorders has been well documented in the Muslim-majority, low-socioeconomic country of Pakistan, the provision of medical genetic services remains limited and cost-prohibitive to the masses in the country. With the objective of identifying gaps in the provision of medical genetics services as perceived by the healthcare providers and the general public, the Pakistani Society of Medical Genetics and Genomics (PSMG) organized a needs assessment webinar on December 6, 2020, titled, "A Vibrant Discussion on the Current Status and Future Needs of Medical Genetic Services in Pakistan." The objectives of the webinar were (1) to explore the current availability of medical genetics services, (2) to identify areas in clinical genetics delivery models needed to improve the state of medical genetics in the country, and (3) to garner the interest in such provisions from the expert and lay audience.

The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.

Background: Preterm birth remains the major cause of neonatal death worldwide. South Asia contributes disproportionately to deaths among preterm births worldwide, yet few population-based studies have assessed the underlying causes of deaths. Novel evaluations, including histological and bacteriological assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of preterm deaths.

Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project.

Background: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.

Methods: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan.

The causes of stillbirths in south Asia: results from a prospective study in India and Pakistan (PURPOSe).

Background: South Asia contributes more than a third of all global stillbirths, yet the causes remain largely unstudied in this region. New investigations, including novel assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of stillbirth. We sought to assess underlying and contributing causes of stillbirth from settings in India and Pakistan.

Early suspicion can save lives; mucormycosis in two children with diabetic ketoacidosis in Pakistan.

Mucormycosis is a cause of fulminant necrotising fungal infection in children with underlying immunocompromising conditions. Rhino-orbito-cerebral infection is its most common form in the paediatric group with uncontrolled diabetes mellitus or diabetic ketoacidosis. The initial presentation can mimic a bacterial infection; thus a high index of suspicion is needed for timely intervention to reduce morbidity and mortality.

Birth asphyxia is under-rated as a cause of preterm neonatal mortality in low- and middle-income countries: A prospective, observational study from PURPOSe.

Objective: To assess respiratory distress syndrome (RDS) compared with birth asphyxia as the cause of death in preterm newborns, assigned by the neonatal intensive care unit (NICU) physician at the time of death and assigned by a panel with complete obstetric history, placental evaluation, tissue histology and microbiology.

Design: Prospective, observational study.

Settings: Study NICUs in India and Pakistan.

Increased dosage and treatment time of Epigallocatechin-3-gallate (EGCG) negatively affects skeletal parameters in normal mice and Down syndrome mouse models.

Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of DYRK1A, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of Dyrk1a and treatment with ~9 mg/kg/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice.

Access to fludrocortisone and to hydrocortisone in children with congenital adrenal hyperplasia in the WHO Eastern Mediterranean Region: it takes a village….

Congenital adrenal hyperplasia (CAH), if untreated, carries high morbidity and mortality. A higher incidence of CAH is expected in countries where consanguinity is common, such as in the countries of the WHO Eastern Mediterranean Region (EMRO). CAH is managed through lifelong treatment with fludrocortisone and hydrocortisone.

Peak Growth Hormone Level Variability during Insulin Tolerance Test in Children with Short Stature.

Objective: To determine the variations in peak growth hormone levels during insulin tolerance test (ITT) in diagnosis of growth hormone deficiency (GHD) in children presenting with short stature.

Study Design: Descriptive study.

Place And Duration Of Study: Department of Pediatric Endocrinology, National Institute of Child Health (NICH), from January to December 2018.

Monogenic diabetes in Pakistani infants and children: challenges in a resource poor country.

Objectives: To review the data of infants and children with suspected monogenic diabetes who underwent genetic testing.

Methods: Monogenic diabetes is a rare form of diabetes resulting from mutations in a single gene. It can be caused by dominant as well as recessive modes of inheritance.

Van Wyk Grumbach Syndrome.

Van Wyk Grumbach syndrome is well known for protracted hypothyroidism, characterised by multicystic ovaries (normal size ovaries contain many follicles of various sizes), isosexual precocious puberty and delayed skeletal growth. A series of ten children with Van Wyk Grumbach syndrome is been presented with their clinical features, biochemical and radiological profile and management. Patients showed a noteworthy improvement upon thyroxine therapy.

Typhoid and Paratyphoid Cost of Illness in Pakistan: Patient and Health Facility Costs From the Surveillance for Enteric Fever in Asia Project II.

Background: The objective of this study was to estimate the cost of illness from enteric fever (typhoid and paratyphoid) at selected sites in Pakistan.

Methods: We implemented a cost-of-illness study in 4 hospitals as part of the Surveillance for Enteric Fever in Asia Project (SEAP) II in Pakistan. From the patient and caregiver perspective, we collected direct medical, nonmedical, and indirect costs per case of enteric fever incurred since illness onset by phone after enrollment and 6 weeks later.

Spectrum of Addison's Disease in Children.

Objective: To determine the clinical presentation of Addison's disease in order to increase the awareness of presentation in Pakistani children.

Study Design: Observational study.

Place And Duration Of Study: Department of Diabetes and Endocrinology, National Institute of Child Health, Karachi, Pakistan, from 2015 to 2019.

We All Have a Role to Play: Redressing Inequities for Children Living with CAH and Other Chronic Health Conditions of Childhood in Resource-Poor Settings.

CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve quality of life for children living with congenital adrenal hyperplasia (CAH). This exploratory case study uses the Knowledge to Action (KTA) framework to analyse CLAN's activities for children living with CAH in the Asia Pacific.

Analysis of variants in GATA4 and FOG2/ZFPM2 demonstrates benign contribution to 46,XY disorders of sex development.

Background: GATA-binding protein 4 (GATA4) and Friend of GATA 2 protein (FOG2, also known as ZFPM2) form a heterodimer complex that has been shown to influence transcription of genes in a number of developmental systems. Recent evidence has also shown these genes play a role in gonadal sexual differentiation in humans. Previously we identified four variants in GATA4 and an unexpectedly large number of variants in ZFPM2 in a cohort of individuals with 46,XY Differences/Disorders of Sex Development (DSD) (Eggers et al, Genome Biology, 2016; 17: 243).

Perceptions of health professionals regarding minimally invasive tissue sampling (MITS) to identify the cause of death in stillbirths and neonates: results from a qualitative study.

Background: Pakistan is considered to be one of the riskiest places in the world for childbirth as measured by its high stillbirth and neonatal mortality rates. Complete diagnostic autopsy remains the gold standard to determine the cause of death (CoD); however, it is not routinely implemented due to religious objections, sociocultural beliefs, limited resources and low demand from physicians and families. Recently, minimally invasive tissue sampling (MITS) using needle biopsies of multiple tissues to obtain tissue for histological examination and organism identification with PCR has been developed and promoted to determine CoD in low-resource areas.

Management of disorders of sex development - With a focus on development of the child and adolescent through the pubertal years.

Disorders of sex development, congenital conditions in which chromosomal, gonadal or anatomic sex is atypical at birth, require urgent assessment by a multidisciplinary team, to define whether there is a life threatening disorder of congenital adrenal hyperplasia or a healthy child with a complex condition. Uncertainty, stigma and taboo complicate counselling which must be knowledgeable, comprehensive and sensitive to different circumstances, religions and cultures. This articles will discuss clinical and genetic diagnosis, decisions regarding sex of rearing, ethical dilemmas, medical management of the infant and of the child or adolescent presenting for the first time with a DSD.

Perceptions of parents and religious leaders regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: results from a qualitative study.

Background: Recently, the minimal invasive tissue sampling (MITS) procedure has been developed to support determination of the cause of death as an alternate to conventional autopsy, especially in countries where complete diagnostic autopsy is not routine. To assess the feasibility of implementation of the MITS procedure for a study to determine cause of death in premature births and stillbirths in south Asia, we explored the views and perceptions of parents and religious leaders on the acceptability of MITS.

Methods: A qualitative study was conducted at the National Institute of Child Health (NICH) hospital of Karachi, Pakistan.

Functional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,XY differences of sex development.

Background: () gene variants are known to cause 46,XY differences/disorders of sex development (DSD). We have identified six patients with 46,XY DSD with seven novel gene variants. Many of these variants were classified as variants of uncertain significance due to their heterozygosity or associated milder phenotype.

Comparison of Classical and Non-Classical Turner Syndrome at NICH Karachi.

Objective: To analyse chromosomal abnormalities of the patients who were referred for the screening of short stature and delayed puberty and to verify the association between karyotype and phenotype in confirmed Turner Syndrome (TS) patients.

Study Design: Descriptive study.

Place And Duration Of Study: Department of Pediatric Endocrinology and Diabetes Unit-II, National Institute of Child Health, Karachi, from January 2011 to June 2016.

Perceptions of parents and healthcare professionals regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: a qualitative study protocol.

Background: Globally, around 2.6 million neonatal deaths occur world-wide every year and the numbers of stillbirths is almost similar. Pakistan is ranked among the highest countries in the world for neonatal mortality.

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.