Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar.

BACKGROUND: Pregnancy is governed by multiple molecular and cellular processes, which might influence pregnancy health and outcomes. Failure to predict and understand the cause of pregnancy complications, adverse pregnancy outcomes, infant's morbidity and mortality, have limited effective interventions. Integrative multi-omics technologies provide an unbiased platform to explore the complex molecular interactions with an unprecedented depth. The objective of the present protocol is to build a longitudinal mother-baby cohort and use multi-omics technologies to help identify predictive biomarkers of adverse pregnancy outcomes, early life determinants and their effect on child health. METHODS/DESIGN: One thousand pregnant women with a viable pregnancy in the first trimester (6-14 weeks of gestation) will be recruited from Sidra Medicine hospital. All the study participants will be monitored every trimester, at delivery, and one-year post-partum. Serial high-frequency sampling, including blood, stool, urine, saliva, skin, and vaginal swabs (mother only) from the pregnant women and their babies, will be collected. Maternal and neonatal health, including mental health and perinatal growth, will be recorded using a combination of questionnaires, interviews, and medical records. Downstream sample processing including microbial profiling, vaginal immune response, blood transcriptomics, epigenomics, and metabolomics will be performed. DISCUSSION: It is expected that the present study will provide valuable insights into predicting pregnancy complications and neonatal health outcomes. Those include whether specific microbial and/or epigenomics signatures, immune profiles are associated with a healthy pregnancy and/or complicated pregnancy and poor neonatal health outcome. Moreover, this non-interventional cohort will also serve as a baseline dataset to understand how familial, socioeconomic, environmental and lifestyle factors interact with genetic determinants to influence health outcomes later in life. These findings will hold promise for the diagnosis and precision-medicine interventions.

Management of fetal malposition in the second stage of labor: a propensity score analysis.

OBJECTIVE: We sought to determine the factors associated with selection of rotational instrumental vs cesarean delivery to manage persistent fetal malposition, and to assess differences in adverse neonatal and maternal outcomes following delivery by rotational instruments vs cesarean delivery. STUDY DESIGN: We conducted a retrospective cohort study over a 5-year period in a tertiary United Kingdom obstetrics center. In all, 868 women with vertex-presenting, single, liveborn infants at term with persistent malposition in the second stage of labor were included. Propensity score stratification was used to control for selection bias: the possibility that obstetricians may systematically select more difficult cases for cesarean delivery. Linear and logistic regression models were used to compare maternal and neonatal outcomes for delivery by rotational forceps or ventouse vs cesarean delivery, adjusting for propensity scores. RESULTS: Increased likelihood of rotational instrumental delivery was associated with lower maternal age (odds ratio [OR], 0.95; P < .01), lower body mass index (OR, 0.94; P < .001), lower birthweight (OR, 0.95; P < .01), no evidence of fetal compromise at the time of delivery (OR, 0.31; P < .001), delivery during the daytime (OR, 1.45; P < .05), and delivery by a more experienced obstetrician (OR, 7.21; P < .001). Following propensity score stratification, there was no difference by delivery method in the rates of delayed neonatal respiration, reported critical incidents, or low fetal arterial pH. Maternal blood loss was higher in the cesarean group (295.8 ± 48 mL, P < .001). CONCLUSION: Rotational instrumental delivery is often regarded as unsafe. However, we find that neonatal outcomes are no worse once selection bias is accounted for, and that the likelihood of severe obstetric hemorrhage is reduced. More widespread training of obstetricians in rotational instrumental delivery should be considered, particularly in light of rising cesarean delivery rates.

Exploring ChatGPT's Potential in Facilitating Adaptation of Clinical Guidelines: A Case Study of Diabetic Ketoacidosis Guidelines.

Background This study aimed to evaluate the efficacy of ChatGPT, an advanced natural language processing model, in adapting and synthesizing clinical guidelines for diabetic ketoacidosis (DKA) by comparing and contrasting different guideline sources. Methodology We employed a comprehensive comparison approach and examined three reputable guideline sources: Diabetes Canada Clinical Practice Guidelines Expert Committee (2018), Emergency Management of Hyperglycaemia in Primary Care, and Joint British Diabetes Societies (JBDS) 02 The Management of Diabetic Ketoacidosis in Adults. Data extraction focused on diagnostic criteria, risk factors, signs and symptoms, investigations, and treatment recommendations. We compared the synthesized guidelines generated by ChatGPT and identified any misreporting or non-reporting errors. Results ChatGPT was capable of generating a comprehensive table comparing the guidelines. However, multiple recurrent errors, including misreporting and non-reporting errors, were identified, rendering the results unreliable. Additionally, inconsistencies were observed in the repeated reporting of data. The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention. Conclusions Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation. Future research should focus on improving the accuracy and reliability of ChatGPT, as well as exploring its potential applications in other areas of clinical practice and guideline development.

Advancing Artificial Intelligence for Clinical Knowledge Retrieval: A Case Study Using ChatGPT-4 and Link Retrieval Plug-In to Analyze Diabetic Ketoacidosis Guidelines.

Introduction This case study aimed to enhance the traceability and retrieval accuracy of ChatGPT-4 in medical text by employing a step-by-step systematic approach. The focus was on retrieving clinical answers from three international guidelines on diabetic ketoacidosis (DKA). Methods A systematic methodology was developed to guide the retrieval process. One question was asked per guideline to ensure accuracy and maintain referencing. ChatGPT-4 was utilized to retrieve answers, and the 'Link Reader' plug-in was integrated to facilitate direct access to webpages containing the guidelines. Subsequently, ChatGPT-4 was employed to compile answers while providing citations to the sources. This process was iterated 30 times per question to ensure consistency. In this report, we present our observations regarding the retrieval accuracy, consistency of responses, and the challenges encountered during the process. Results Integrating ChatGPT-4 with the 'Link Reader' plug-in demonstrated notable traceability and retrieval accuracy benefits. The AI model successfully provided relevant and accurate clinical answers based on the analyzed guidelines. Despite occasional challenges with webpage access and minor memory drift, the overall performance of the integrated system was promising. The compilation of the answers was also impressive and held significant promise for further trials. Conclusion The findings of this case study contribute to the utilization of AI text-generation models as valuable tools for medical professionals and researchers. The systematic approach employed in this case study and the integration of the 'Link Reader' plug-in offer a framework for automating medical text synthesis, asking one question at a time before compilation from different sources, which has led to improving AI models' traceability and retrieval accuracy. Further advancements and refinement of AI models and integration with other software utilities hold promise for enhancing the utility and applicability of AI-generated recommendations in medicine and scientific academia. These advancements have the potential to drive significant improvements in everyday medical practice.

Examining Feasibility, Acceptability, and Preliminary Outcomes of a Culturally Adapted Evidence-Based Postpartum Depression Preventive Intervention for Women in Doha, Qatar: Protocol for a Randomized Controlled Trial.

BACKGROUND: Postpartum depression and anxiety are the 2 most common perinatal mental health disorders, with prevalence rates higher among women living in the Middle East than in most Western countries. The negative outcomes associated with postpartum depression and anxiety are profound and include less responsive parenting and compromised infant and young child development. Although interventions exist to prevent postpartum depression and anxiety, to date, there have been no studies that have attempted to prevent postpartum depression or anxiety among Arabic-speaking women in the Middle East, including Qatar. OBJECTIVE: The purpose of this study is to conduct a randomized controlled trial (RCT) of an evidence-based postpartum depression preventive intervention-Mothers and Babies (MB)-culturally adapted for use with Arabic-speaking women in Doha, Qatar. MB is guided by a cognitive behavioral therapy framework that focuses on increasing pleasant activities, promoting healthy thought patterns, and increasing the type and frequency of personal contacts. MB is tailored to specific needs and issues related to pregnancy and the postpartum period. METHODS: A multidisciplinary and multiethnic investigator team adapted MB to promote cultural and contextual fit for Arabic-speaking women. Intervention concepts were reviewed to ensure core content would be understood by Arabic-speaking women in Qatar. Subsequently, images, activities, and examples in the intervention manuals were adapted, as needed, to make the content more relevant to Arab culture. To deliver the adapted intervention, 30 Arabic-speaking individuals with mental health backgrounds were trained. The adapted intervention was subsequently pilot-tested with 10 pregnant women receiving prenatal care at Sidra Hospital in Doha. We are now conducting an RCT to examine the effectiveness of the adapted intervention. We plan to enroll 210 pregnant individuals who are Arabic-speaking, with 1:1 randomization to the MB intervention or usual prenatal care. Among the enrolled participants, a stratified subsample of 40 pregnant women with diabetes is being recruited. Data collection will take place at baseline and a 6-month follow-up. The primary outcomes are depressive and anxiety symptoms and perceived stress. Diabetes self-care is the exploratory outcome for the subsample of individuals with diabetes. Intervention implementation will be assessed via client and provider surveys during and after intervention delivery. Power and sample size were calculated using a 2-sided 5% effort rate and assumed analyses on the individual level, accounting for attrition of 20%. RESULTS: The cultural adaptation and pilot study of the adapted MB intervention are completed. A total of 157 women have been enrolled in the RCT as of March 31, 2023. CONCLUSIONS: This study is highly innovative, as it is the first study to our knowledge to examine the effectiveness of an evidence-based postpartum depression preventive intervention in the Middle East. Limitations include a single follow-up time point and a small subsample of individuals with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04442529; https://www.clinicaltrials.gov/study/NCT04442529. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11623.

Intraumbilical injection of three different uterotonics in the management of retained placenta.

AIM: The aim of this work was to compare the effect of intraumbilical injection of three different uterotonic solutions in the management of retained placenta. MATERIALS AND METHODS: This study was conducted in Ain-Shams University Maternity Hospital, Cairo, Egypt. A total of 78 women with retained placenta (>30 min after delivery of the fetus) were included in the study and subdivided into three groups. Each group was injected with a different type of uterotonic into the umbilical vein after clamping it using the Pipingas technique. Uterotonics used were either 20 IU oxytocin dissolved in 30 mL saline (n=26), ergometrine 0.2 mg dissolved in 30 mL saline (n=27) or misoprostol 800 µg dissolved in 30 mL saline (n=25). RESULTS: The overall success rate of spontaneous placental separation within 30 min after intraumbilical injection of uterotonics was 56/78 (71.79%). The success rate was higher with misoprostol when compared to oxytocin and ergometrine but the difference was not significant (20/25 [80%], 19/26 [73.08%], 17/27 [62.96%], respectively, P>0.05). The injection-to-separation interval was significantly shorter in the misoprostol group than in the oxytocin and ergometrine groups (7.0±2.2 min, 13.14±3.76 min, 22.5±4.37 min, respectively, P<0.001). CONCLUSION: Intraumbilical injection of uterotonics, namely oxytocin, ergometrine and dissolved misoprostol in saline, are closely effective in the management of retained placenta, with misoprostol being slightly more effective. This method may have a role in minimizing the need for manual removal of the placenta and its adverse sequelae.

Implications of non-invasive prenatal testing for identifying and managing high-risk pregnancies.

Non-invasive prenatal testing is regularly used to screen for aneuploidies and Rhesus status of a fetus. Since 1997 when free fetal DNA (ffDNA) in the maternal circulation was first identified, it has been hypothesized that it may be possible to use non-invasive prenatal testing (NIPT) to identify high-risk pregnancies including pre-eclampsia, growth restriction and preterm birth. Since then there has been much interest in this area as a way to identify and understand disease processes. This review presents the current evidence for this approach. For pre-eclampsia the hypothesis is that ffDNA would increase but the evidence for this is heterogenous across studies and trimesters. There is however increasing agreement between studies that by the third trimester ffDNA is more likely to be raised in pre-eclamptic patients than controls. For preterm birth, again, the main hypothesis is that ffDNA should increase. The results are also heterogenous, with some studies finding increased ffDNA prior to preterm birth, and others finding no change. For fetal growth restriction, there are competing theories for reduced and increased ffDNA and some studies suggest that levels are raised and some reduced. There are complexities in interpreting all of this evidence as the studies' designs, patient populations, and especially in the context of growth restriction, the definitions are not clear. Furthermore, authors use different biochemical tests and different units to describe their results, making meta-analysis difficult. All of these issues and conflicting findings lead us to the conclusion that currently there is yet no definitive place in clinical practice for NIPT to support the diagnosis and management of high-risk pregnancies. However, it is vital that this research continues as it could open the door to better understanding of the disease process and novel approaches to management.

Non invasive prenatal testing (NIPT) for common aneuploidies and beyond.

Non invasive prenatal Testing (NIPT) is changing the practice of prenatal diagnosis worldwide. It provides high sensitivity and specificity in screening for common aneuploidies. As a result, it has reduced the number of invasive procedures, thereby reducing their associated risk of pregnancy miscarriage. NIPT is based on the detection and analysis of cell free fetal DNA (cffDNA) that is obtained from a maternal peripheral blood sample. Advanced laboratory detection and purification technology has improved the performance of NIPT and allowed the introduction of new applications in recent years. The introduction of Next Generation Sequencing (NGS) into clinical practice has rendered NIPT to have high sensitivity in the screening of aneuploidy. It has also allowed detecting and investigating the fetal genome from maternal plasma. Fetal Whole Exome Sequencing (WES) provides non invasive prenatal diagnosis of inherited monogenic disorders and can also offer a diagnosis of an underlying cause of fetal anomalies that have a normal karyotype. The following will review the current and potential future applications of NIPT and discuss the advantages and disadvantages of the various NIPT techniques. The role of public healthcare system plays in the provision of the test, and the psychological impact of NIPT on the end-users will also be highlighted.

The SAFE project: towards non-invasive prenatal diagnosis.

After the revolutionary detection of ffDNA (free fetal DNA) in maternal circulation by real-time PCR in 1997 and advances in molecular techniques, NIPD (non-invasive prenatal diagnosis) is now a clinical reality. Non-invasive diagnosis using ffDNA has been implemented, allowing the detection of paternally inherited alleles, sex-linked conditions and some single-gene disorders and is a viable indicator of predisposition to certain obstetric complications [e.g. PET (pre-eclampsia)]. To date, the major use of ffDNA genotyping in the clinic has been for the non-invasive detection of the pregnancies that are at risk of HDFN (haemolytic disease of the fetus and newborn). This has seen numerous clinical services arising across Europe and many large-scale NIPD genotyping studies taking place using maternal plasma. Because of the interest in performing NIPD and the speed at which the research in this area was developing, the SAFE (Special Non-Invasive Advances in Fetal and Neonatal Evaluation) NoE (Network of Excellence) was founded. The SAFE project was set up to implement routine, cost-effective NIPD and neonatal screening through the creation of long-term partnerships within and beyond the European Community and has played a major role in the standardization of non-invasive RHD genotyping. Other research using ffDNA has focused on the amount of ffDNA present in the maternal circulation, with a view to pre-empting various complications of pregnancy. One of the key areas of interest in the non-invasive arena is the prenatal detection of aneuploid pregnancies, particularly Down's syndrome. Owing to the high maternal DNA background, detection of ffDNA from maternal plasma is very difficult; consequently, research in this area is now more focused on ffRNA to produce new biomarkers.

Quantification of cell free fetal DNA in maternal plasma in normal pregnancies and in pregnancies with placental dysfunction.

OBJECTIVE: To assess the normal levels of free fetal DNA in maternal plasma through pregnancy compared with those in pregnancies complicated with placental dysfunction manifested by preeclampsia and/or fetal growth restriction. STUDY DESIGN: Maternal blood samples from 138 singleton male pregnancies were divided into 3 groups; normal pregnancies (77), preeclampsia (49), and fetal growth restriction (12). Royston and Wright's methods were used to calculate gestational age-related reference limits of free fetal DNA in the 3 groups. The DYS14 gene of the Y chromosome was quantified and compared in maternal plasma by using real-time quantitative polymerase chain reaction. RESULTS: Free fetal DNA in normal pregnancies increased with gestational age. Results were significantly higher in preeclampsia and fetal growth restriction groups than in normal pregnancy and were higher in severe preeclampsia than in milder disease. CONCLUSION: Free fetal DNA is a potential marker for placental dysfunction in pregnancy. Large prospective studies are now needed to investigate its role in the prediction of pregnancy complications and severity and or timing of delivery.

Cardiac function in early onset small for gestational age and growth restricted fetuses.

OBJECTIVE: To examine cardiac function in appropriately grown, small for gestational age and intrauterine growth restricted fetuses and investigate the relationship between cardiac function and fetal arterial and venous Doppler parameters. STUDY DESIGN: Myocardial performance index, isovolumetric contraction time, isovolumetric relaxation time, ejection time, and umbilical artery, middle cerebral artery and ductus venosus Doppler pulsatility index were measured for women between 24 and 32 weeks with small for gestational age and intrauterine growth restricted fetuses. Forty-eight appropriately grown, 11 small for gestational age and 12 intrauterine growth restricted cases were included. The relationship between cardiovascular parameters and gestation was defined and Doppler values converted to Z-scores in relation to gestational age. RESULTS: In small for gestational age fetuses and fetuses with intrauterine growth restriction the myocardial performance index was 0.66 (0.63-0.7) and 0.64 (0.60-0.67), respectively, and compared to appropriately grown fetuses, at 0.45 (0.43-0.47), was significantly increased (p=0.001). No relationship was found between the myocardial performance index and arterial and venous Doppler Z-score. CONCLUSION: Small for gestational age and intrauterine growth restricted fetuses demonstrate altered cardiac function in the late second and early third trimester of pregnancy. Importantly, the myocardial performance index is raised in small for gestational age fetuses before the arterial and venous Doppler abnormalities that characterize hypoxia are evident.