Evolution of foetal echocardiography as a screening tool for prenatal diagnosis of congenital heart disease

Congenital cardiac anomalies are the most common anomalies, with an estimated incidence of about 4-13 per 1000 live births. Proper perinatal and neonatal management is dependent upon accurate prenatal diagnosis. Approximately 10% of foetuses with cardiac abnormalities have identified risk factors; hence, most of the anomalies occur in pregnancies without prenatal risk factors. Foetal echocardiography allows for prenatal diagnosis of congenital heart disease and serves as a routine screening tool for congenital heart defects. Advanced technology, has not only allowed more accurate and early detection of cardiac abnormalities but has also improved the care and outcome of selected foetuses with severe cardiac malformations or arrhythmias. It can also identify patients for in-utero cardiac interventions. Prenatal diagnosis of congenital heart disease has allowed for better counseling and preparation of families regarding the expected prenatal development of the foetus as well as the anticipated postnatal management strategy and prognosis

A biological model of fetomaternal haemorrhage for the development of first-trimester non-invasive prenatal diagnosis

Ph.DDOCTOR OF PHILOSOPH

The efficacy of a personalized mhealth coaching program during pregnancy on maternal diet, supplement use, and physical activity: Protocol for a parallel-group randomized controlled trial

Background: Adequate intake of macro- and micronutrients and adoption of an active lifestyle during pregnancy are essential for optimum maternal and fetal health and offspring development. Dietary counseling and advice regarding adequate physical activity are integral components of antenatal care. Personalized coaching through the use of mobile health (mHealth) that supports behavior modification is an innovative approach that needs exploration.Objective: Our primary aim is to assess the efficacy of an mHealth program in improving diet, supplement use, and physical activity during pregnancy. Secondary objectives include evaluation of the program\u27s effect on maternal and offspring health outcomes and assessment of its compliance and usability.Methods: A randomized controlled trial was initiated at the Aga Khan University Hospital in Karachi, Pakistan, in January 2020. We aim to recruit 300 pregnant women in their first trimester who have smartphones, do not have comorbidities, and are not taking medications. The intervention group will be trained to use an mHealth app called PurUmeed Aaghaz. Through this app, the subjects will report information about their diet, supplement use, and physical activity and will receive personalized advice and three push messages as weekly reminders. The research assistant will obtain similar information from the control group via a paperless questionnaire; this group will receive standard face-to-face counseling regarding diet, supplement use, and physical activity. Data will be collected at enrollment and during four follow-up sessions scheduled 6 weeks apart. Primary study outcomes include improvements in diet (ie, change in mean dietary risk score from baseline to each follow-up), supplement use (ie, changes in mean supplement use score and biochemical levels of folic acid, iron, calcium, and vitamin D on a study subset), and mean duration of reported physical activity (minutes). Secondary study outcomes relate to maternal health (ie, gestational diabetes mellitus, gestational hypertension, pre-eclampsia, and gestational weight gain), newborn health (ie, birth weight and length and gestational age at delivery), and infant health (ie, BMI and blood pressure at 1 year of age). Compliance will be determined by the proportion of participants who complete the 6-month coaching program. Usability will be assessed based on features related to design, interface, content, coaching, perception, and personal benefit.Results: The study was approved by the Ethics Review Committee of the Aga Khan University in 2017. The recruitment of study participants was completed in September 2021. All follow-ups and outcome assessments are expected to be completed by March 2023 and analysis is expected to be completed by June 2023. We expect the results to be published by the end of 2023.Conclusions: This study will be an important step toward evaluating the role of mHealth in improving behaviors related to a healthy diet, supplement use, and promotion of physical activity during pregnancy, as well as in influencing maternal and offspring outcomes. If proven effective, mHealth interventions can be scaled up and included in antenatal care packages at tertiary care hospitals of low- and middle-income countries.Trial registration: ClinicalTrials.gov NCT04216446; https://clinicaltrials.gov/ct2/show/NCT04216446.International registered report identifier (irrid): DERR1-10.2196/31611

Impact of pre-eclampsia on the cardiovascular health of the offspring: a cohort study protocol

Introduction: Pre-eclampsia is a common disorder associated with serious maternal and fetal complications. It is associated with abnormal placentation, which significantly reduces flow, resulting in a relative hypoxic state. These pathophysiological changes lead to subtle macrovascular and cardiac structural and functional changes in the fetus. This can predispose the child with maternal history of pre-eclampsia to risk of premature cardiovascular disease.Methods and analysis: The children will be identified from a cohort of women with pre-eclampsia. The study will be conducted at The Aga Khan University Hospital, Karachi. Inclusion criteria will be children who are between 2 and 5 years of age and have a maternal history of pre-eclampsia. The child’s current weight, height and blood pressure will be recorded. A two-dimensional functional echocardiogram and vascular assessment will be performed to evaluate alterations in cardiac function as well as macrovascular remodelling in these children. Data will be presented as mean±SD, median (IQR) or percentages as appropriate. Independent t-test or Mann-Whitney U test will be used for testing of continuous variables (based on the assumption of normality). A p\u3c0.05will be used to determine statistical significance.Ethics and dissemination: Ethical approval has been obtained from AKUH Ethics Review Committee. Findings will be disseminated through scientific publications and project summaries for the participants

Follicular sensitivity index: A tool to predict successful conception after intra-cytoplasmic sperm injection

Follicular sensitivity index (FSI) is used for estimation of follicular responsiveness to controlled ovarian hyperstimulation (COH) during intra-cytoplasmic sperm injection (ICSI). In a retrospective study, FSI of 1,385 females was calculated as [pre-ovulatory follicle count (PFC) × 100,000]/ [antral follicle count (AFC) × total received stimulation doses]. Females were then categorised into low, middle and high FSI groups according to FSI tertile values. FSI was 8.65 ±2.82 in non-pregnant as compared to 12.02 ±2.04 (p \u3c0.01) in pregnant cohort. FSI turned out to be a strong predictor of successful conception on the receiver operating curve with cutoff value 10.36 at 76% specificity, sensitivity of 86% and area under the curve (AUC; 0.83). Calculation of FSI can thus predict the chances of successful conception in females with different causes of infertility

Non-invasive prenatal determination of fetal RhD genotyping from maternal plasma: a preliminary study in Pakistan

Objectives: To determine the accuracy of the non-invasive pre-natal real-time polymerase chain reaction based fetal RhD genotyping from maternal plasma. Study Design: Cross-sectional study. Place And Duration Of Study: Juma Health Sciences Research Laboratory, The Aga Khan University Hospital, Karachi, from July to December 2008. Methodology: Cell-free plasma DNA from 21 D-negative women with D-positive spouse between 20-39 weeks of gestation was tested for the presence of exon 5 region of RhD gene using real-time polymerase chain reaction. b-globin was employed as the house-keeping gene. Sensitivity and specificity of the real-time PCR-based non-invasive fetal RhD genotyping was obtained by calculating proportion of the D-positive fetuses that were D-positive at birth as well. Results: Of the 21 D-negative women 13 and 8 neonates were determined to be D-positive and D-negative, respectively, by serologic studies on cord blood samples at birth. RhD status was correctly determined in 17 of 21 cases. There were three false-positive and one false-negative results. The sensitivity and specificity of the assay was 92.3% (95% CI: 62.1, 99.6) and 62.5% (95% CI: 25.9, 89.8), respectively. The positive and negative predictive value of the assay was 80% (95% CI: 51.4, 94.7) and 83.3% (36.5, 99.1), respectively. Conclusion: These preliminary results demonstrate the feasibility of non-invasive pre-natal diagnosis of fetal RhD status of D-negative mothers in Pakistan

Isolation and culture of dental pulp stem cells from permanent and deciduous teeth

OBJECTIVE: To isolate dental pulp mesenchymal stem cells (MSCs) from non-infected human permanent and deciduous teeth. METHODS: It was an in-vitro experimental study. Human teeth were collected from 13 apparently healthy subjects including nine adults and four children. After decoronation dental pulps were extirpated from teeth and cultured via explant method in a stem cell defined media. Data was analyzed by descriptive statistics. RESULTS: As above MSCs emerged exhibiting fibroblast-like morphology. In vitro culture was positive for 100% (9/9) and 75% (3/4) of the permanent and deciduous teeth respectively. First cell appeared from deciduous teeth pulp in 10±6.2 days while permanent teeth pulp took 12.4±3.7 days. Together, 26.6±3.6 and 24.5±3.5 days were required for permanent and deciduous tooth pulp stem cells to be ready for further assays. CONCLUSIONS: The protocol we developed is easy and consistent and can be used to generate reliable source of MScs for engineering of calcified and non-calcified tissue for regenerative medicine approaches.

Pakistan developmental origins of health and disease (DOHaD) society: Addressing the \u27DO\u27 component of DOHaD

Adverse intrauterine environment could serve as an important stimulus for postnatal altered health status and for increased susceptibility to long-term non-communicable diseases (NCDs). The notion is now recognized as the Developmental Origins of Health and Disease (DOHaD), which was first proposed by Sir David Barker. Since then, several scientific disciplines have strived to measure the magnitude of the early fetal programming and later risk of diseases. Pakistan, with striking figures of morbidity and mortality from NCDs, is currently tackling with double burden of diseases and requires planned efforts to counteract the threat of NCDs. Considering the growing needs and available evidences, Pakistan DOHaD Society was officially instigated in September 2016. The Society aims to explicitly address the association of life in utero with future health and disease and to endorse early screening and interventions to reduce the burden of NCDs, mental health issues and learning disorders along the life course. It has shown significant progress toward investigating the influence of adverse in utero environment such as diabetes, maternal under-nutrition and pre-eclampsia on fetal programming under two major research lines, that is, cardiovascular and cerebrovascular programming. The Society has been successful in disseminating its research findings through several esteemed international scientific conferences. Pakistan DOHaD Society encourages scientific community for collaborative research aimed at improving the quality of life during early childhood, adolescence and adulthood through provision of appropriate pre-pregnancy and antenatal interventions targeted to address at-risk in utero conditions

Influence of intrauterine growth status on aortic intima-media thickness and aortic diameter in near-term fetuses: A comparative cross-sectional study

Intrauterine undernutrition may lead to fetal vascular programming. We compared abdominal aortic intima-media thickness (aIMT) and aortic diameter (aD) between appropriate for gestational age (AGA) and growth-restricted fetuses (GRF). We recruited 136 singleton fetuses at 34-37 weeks of gestation from Fetal Medicine Unit of Aga Khan University Hospital, Karachi (January-November 2017). Subjects were classified as AGA (n = 102) and GRF (n = 34) using INTER-GROWTH 21st growth reference and standard ultrasound protocol. Their far- and near-wall aIMT and aD were compared after adjustment of maternal age, first-trimester body mass index, fetal gender, hypertension and hyperglycemia in pregnancy. As the severity of growth restriction increased in GRF, aIMT and aD showed an increasing and a decreasing trend, respectively. Both far- and near-wall aIMT in GRF [(adj. β = 0.082, 95% confidence interval [CI] 0.042-0.123) and (adj. β = 0.049, 95% CI 0.010-0.089)] were significantly greater with reference to AGA fetuses. GRF subgroup analysis into small for gestational age (SGA) fetuses and intrauterine growth restricted (IUGR) revealed highly significant difference between AGA and IUGR for far (0.142 mm, P-value \u3c 0.001) and near-wall aIMT (0.115 mm, P-value \u3c 0.001) and marginally significant aD difference (0.51 mm, P-value 0.05). These findings suggest that the extent of fetal aortic remodelling is influenced by the severity of growth restriction. Hence, the targeted interventions for the cardiovascular health promotion of IUGR and SGA born neonates are desirable during early childhood, particularly in set ups with high prevalence of low birth weight babies