Neonatal Hypoglycemia Research Articles

Metformin versus insulin in glycemic control in pregnancy (MevIP): a randomized clinical trial protocol

BackgroundGestational diabetes is one of the most prevalent diseases in pregnancy, with an incidence of 5 to 18% in Brazil, and is associated with high morbidity rates. The first-line treatment is insulin, although some recent studies have indicated that metformin might also be effective. Metformin is safe in pregnancy and appears to produce better results than insulin, including reduced gestational weight gain (GWG) and smaller gestational-age newborns. Few studies have been conducted on this topic in low- and middle-income countries.MethodsWe designed an open randomized controlled trial comparing two treatments for pregnant women with type II diabetes mellitus (DM) and gestational diabetes (DMG): the metformin group (intervention) and the insulin group (as a routine service). The primary outcome is glycemic control. The secondary outcomes are GWG, the occurrence of hypertensive syndromes, macrosomia, and neonatal hypoglycemia. The sample will comprise 92 pregnant women, 46 per group. The inclusion criteria will be GDM or type II DM requiring medication for glycemic control, singleton pregnancy, and gestational age under 34 weeks. The exclusion criteria will be current treatment with any medication for glycemic control, type I DM, and intolerance to the study medications (metformin or insulin). Women will be routinely followed during antenatal care, childbirth, and the postpartum period. Statistical analyses will include the intention-to-treat approach and a comparison between the two groups.DiscussionConsidering the Brazilian socioeconomic reality and the safety of metformin demonstrated in previous trials, we expect that the MevIP study will demonstrate that metformin is an adequate and appropriate medication for GDM treatment in the Brazilian population, representing an alternative to insulin for GDM.Trial registrationThis protocol has been registered prospectively in ReBEC under the ID RBR-3j3cktx in August 11, 2023.

Prevalence of prolonged transitional neonatal hypoglycemia and associated factors in Ethiopia: A systematic review and meta-analysis.

Most neonates experience transient hypoglycemia, which typically responds well to treatment and is associated with a favorable prognosis. However, hypoglycemia persisting beyond 48 hours, termed prolonged transitional Neonatal hypoglycemia (PTNHG), can result in abrupt neuronal injury and long-term neurodevelopmental impairments. Identifying its prevalence and associated risk factors is critical to inform clinical practices and improve neonatal outcomes. A weighted inverse-variance random-effects model was employed for the analysis. Heterogeneity among the studies was assessed using a forest plot, I2 statistics, and Egger's test. Data extraction was conducted from May 20 to May 27, 2023, for studies published since 2020. A random blood sugar (RBS) concentration of <47 mg/dL measured 48-72 hours after birth was used to define PTNHG. Eight studies comprising a total of 3686 neonates were included in the analysis. The pooled prevalence of PTNHG was 19.71% (95% CI: 16.85-22.56) with substantial heterogeneity (I2 = 79.20%, P < 0.001). Subgroup analysis revealed that PTNHG prevalence was similar for studies with sample sizes >400 and ≤400, at 18% (95% CI: 15-22) and 21% (95% CI: 17-26), respectively. Similarly, prevalence estimates were comparable when using RBS thresholds of <47 mg/dL (21%; 95% CI: 16-27) and <40 mg/dL (18%; 95% CI: 15-22). Significant factors associated with PTNHG included preterm birth (AOR = 3.31; 95% CI: 2.57-4.04), hypothermia (AOR = 3.41; 95% CI: 2.19-4.62), being an infant of a diabetic mother (IDM) (AOR = 4.71; 95% CI: 2.15-7.26), delayed breastfeeding initiation beyond one hour (AOR = 3.26; 95% CI: 2.03-4.49), and pathological jaundice (AOR = 2.37; 95% CI: 1.91-2.84). Nearly one-fifth of hospitalized neonates experienced PTNHG. Fortunately, most of the associated risk factors were modifiable. Prioritizing early breastfeeding initiation, particularly in cesarean section deliveries and IDM cases, and integrating PTNHG management into national NICU guidelines could significantly reduce the burden of neonatal hypoglycemia. Prospero ID: CRD42023424953. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023424953.

Formulation, Quality Control and Stability Study of Pediatric Oral Dextrose Gel

Background/Objective: Little information is available on the stability and quality controls of compounded 40% dextrose gel required to ensure its safe use in the treatment and prevention of neonatal hypoglycemia. Whether its efficacy relies on buccal absorption also remains uncertain. This study investigates the stability, microbiological safety, rheological properties and dextrose diffusion of a compounded 40% oral dextrose gel, ensuring it can be widely compounded and stored for clinical use. Methods: A 40% dextrose gel compounded with anhydrous dextrose, carboxymethylcellulose, citric acid, sorbic acid and sterile water was subjected to quality control measures including a dextrose content assay, degradation product analysis, microbiological testing and preservative efficacy. Stability studies were conducted at refrigerated (4–8 °C) and ambient temperatures for 7 days and 3 months, respectively. Rheological properties were assessed, and dextrose permeation was measured through an artificial membrane model that mimics a biological membrane. Results: The compounded gel demonstrated stability for up to 7 days at ambient temperature and 90 days when refrigerated. The dextrose content remained within the acceptable range (90–110%) and microbiological tests confirmed compliance with safety standards. The gel exhibited the consistent rheological properties and shear-thinning behavior appropriate for oral mucosal administration. In vitro permeation studies showed no evidence of dextrose diffusion with a long lag time followed by a low steady-state permeation flux. Conclusions: This study validates the compounding process of a stable 40% oral dextrose gel formulation for neonatal hypoglycemia management, which meets quality control criteria and can be safely administered in clinical practice, offering a cost-effective and safe alternative for neonatal care.

Comprehensive Review of Gestational Diabetes: Pathophysiology, Pharmacological Management and the Role of Pharmaceutical Care.

This review addresses the significant part pharmacological treatment plays in treating gestational diabetes mellitus (GDM), therefore enhancing the results for mother and child. Talking about the frequency and relevance of GDM would help to underline the need for good management. The pathophysiology presents a thorough examination of the fundamental processes, clarifying how hormonal changes seen during pregnancy lead to insulin resistance and raised blood sugar levels. The pharmacological treatment approaches for GDM, including insulin treatment and oral hypoglycemic medications, are investigated in this paper. Taking into consideration the hazards of generating birth deformities and safety data, the paper also evaluates the safety of the drugs in diabetes pregnancy in order to offer best treatment results. Moreover, the function of pharmacists in GDM highlights their significance in patient education, ensuring adherence to medication and overseeing therapy in collaboration with multidisciplinary teams. Furthermore, the impact of pharmaceutical care on maternal and neonatal outcomes demonstrates how pharmaceutical interventions can effectively reduce complications like preeclampsia and neonatal hypoglycemia, highlighting the importance of personalized medication management. Finally, the challenges and future directions of GDM address the difficulties in pharmaceutical care, including patient compliance, healthcare access and emerging treatment methods, calling for more research and policy initiatives to improve pharmaceutical care frameworks and enhance health outcomes for both mothers and infants. This comprehensive review highlights the need for integrated pharmaceutical care in managing GDM and its potential to improve health outcomes for both mothers and infants.

Managing persistent neonatal hyperinsulinemic hypoglycemia: Insights from nesidioblastosis research

Background: Persistent neonatal hyperinsulinemic hypoglycemia (PNHH), frequently associated with nesidioblastosis, poses significant diagnostic and therapeutic challenges due to dysregulated insulin secretion. Congenital hyperinsulinism (CHI), the primary cause of PNHH, exhibits diverse genetic and phenotypic presentations, necessitating tailored management strategies. This review integrates insights from 20 studies, examining genetic, therapeutic, and psychosocial dimensions of CHI. Objectives: To evaluate genotype-phenotype correlations and their implications for therapeutic outcomes in CHI, compare long-term medical and surgical outcomes, and identify risk factors affecting growth, metabolism, and neurodevelopment. Additionally, the study explores effective strategies to address the psychosocial and dietary challenges associated with CHI. Methods: A systematic review of 20 studies, encompassing over 2,000 patients, was conducted. Diagnostic criteria included genetic analyses of mutations in KATP channel genes (ABCC8, KCNJ11), GLUD1, and HNF4A, along with imaging and histopathological assessments. Treatment efficacy, long-term outcomes, and the impact of caregiver burden were analyzed. Data were synthesized into thematic categories, supported by statistical and qualitative assessments. Results: Dominant KATP mutations exhibited high responsiveness to diazoxide (70%), whereas recessive mutations necessitated surgical interventions, particularly near-total pancreatectomy. Focal CHI resolved hypoglycemia effectively with lesionectomy, whereas diffuse CHI presented ongoing risks, including diabetes and neurodevelopmental impairments. Personalized dietary strategies, such as high-protein diets and gastrostomy feeding, were effective in stabilizing glucose levels. Psychological stress in caregivers emerged as a significant concern, emphasizing the need for supportive interventions. Emerging therapies like lanreotide showed promise in refractory CHI cases. Discussion: The findings align with prior research, confirming the role of genetic mutations in determining treatment responsiveness. Surgical interventions, though effective in resolving hypoglycemia, carry long-term metabolic risks. Recent advances in genetic diagnostics and personalized medical therapies highlight opportunities for optimizing outcomes. However, caregiver burden and psychosocial challenges remain underexplored areas that require structured support systems. Conclusion: Managing CHI necessitates a multidisciplinary approach, integrating genetic insights, advanced therapies, and psychosocial support. Continued research is essential to develop innovative solutions for refractory CHI cases and to improve long-term outcomes for patients and families.

Neuroimaging in Infantile Hypoglycemia - How it is Different from Neonatal Hypoglycemia.

Neuroimaging in Infantile Hypoglycemia - How it is Different from Neonatal Hypoglycemia.

Retrospective Analysis of the Correlation between Umbilical Blood Flow Index and Maternal and Fetal Outcomes in Pregnant Women with Gestational Diabetes.

Aims/Background Gestational diabetes mellitus (GDM) is a common complication during pregnancy. This retrospective study investigates the correlation between umbilical blood flow index and maternal-fetal outcomes in pregnant women with GDM, aiming to contribute to evidence-based risk assessment and management strategy in this high-risk obstetric population. Methods This retrospective study recruited 119 pregnant women with GDM who were admitted to the Yichang Central People's Hospital, between January 2022 and January 2024. Based on the umbilical blood flow index, the study participants were divided into a normal umbilical blood flow (UBF) index group (n = 56) and a high UBF index group (n = 63). Colour Doppler ultrasound was used to assess umbilical blood flow, and relevant data on maternal, fetal, and neonatal outcomes were obtained from the hospital's electronic medical records. Results We observed that, compared to the normal UBF index group, the high UBF index group exhibited significantly higher rates of adverse pregnancy outcomes, including the cesarean section (p = 0.022), preterm delivery (p = 0.020), gestational hypertension (p = 0.019), neonatal hypoglycemia (p = 0.015), as well as increased incidence of neonatal complications such as respiratory distress syndrome (p = 0.009), neonatal jaundice (p = 0.022), neonatal intensive care unit (NICU) admission (p = 0.015), lower 5-minute Apgar scores (p = 0.013), and neonatal sepsis (p = 0.005). Furthermore, significant differences were observed in fetal biometric parameters and placental morphology between the two groups (fetal weight: p = 0.003; estimated fetal weight percentile: p = 0.017; femur length: p = 0.018; placental weight: p = 0.019; placental volume: p = 0.021). Additionally, correlation analyses indicated significant associations between umbilical blood flow index and maternal and fetal outcomes (p < 0.05). Conclusion We observed a significant correlation between umbilical blood flow indices and maternal and fetal outcomes in pregnant women with gestational diabetes mellitus, implying its utility as a non-invasive parameter for risk stratification and personalized management in this high-risk obstetric population.

Hybrid remote and in-clinic maternal-fetal surveillance for women with gestational diabetes: A prospective pilot study.

This study explores a hybrid approach to maternal-fetal care for gestational diabetes (GD), integrating virtual visits seamlessly with in-clinic assessments. We assessed the feasibility, time efficiency, patient satisfaction, and clinical outcomes to facilitate wider adoption of maternal-fetal telemedicine. We conducted a 4-week prospective study involving 20 women with GD at ≥32 weeks of pregnancy, alternating between remote and in-clinic weekly visits. Remote assessments began with women self-measuring vital signs and using a digital urine dipstick. The remote encounter started with a midwife performing anamnesis and remotely connecting women to the fetal nonstress test. A physician concluded the meeting with remote sonographic assessment of amniotic fluid maximal vertical pocket that together with the nonstress test provided the modified biophysical assessment as well as a video encounter and ongoing glycemic control assessment. We assessed the feasibility of remote visits, compared visit durations, evaluated women's satisfaction using the Telehealth Usability Questionnaire, examined glucose documentation adherence during hybrid care compared with the following period until birth, and assessed GD-related clinical outcomes. Remote visits had a success rate of 97.4% (38 of 39), with significantly shorter durations compared with in-clinic visits (median 59.0 min vs. 159.0 min, P < 0.001). Women expressed high satisfaction (6.6 of 7), and adherence with recording fasting glucose values during the study period was significantly higher than the following period until birth (92.2% vs. 61.8%, P = 0.001). Notably, none required induction of labor for glycemic control imbalance, and there were no cases of macrosomia, shoulder dystocia, or neonatal hypoglycemia. The hybrid approach to maternal-fetal care for GD demonstrated feasibility, safety, time efficiency, improved patient satisfaction, and enhanced glycemic control adherence.

Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications.

Gestational diabetes mellitus (GDM) affects over 10% of all pregnancies, both in Korea and worldwide. GDM not only increases the risk of adverse pregnancy outcomes such as preeclampsia, preterm birth, macrosomia, neonatal hypoglycemia, and shoulder dystocia, but it also significantly increases the risk of developing postpartum type 2 diabetes mellitus and cardiovascular disease in the mother. Additionally, GDM is linked to a higher risk of childhood obesity and diabetes in offspring, as well as neurodevelopmental disorders, including autistic spectrum disorder. This review offers a comprehensive summary of clinical epidemiological studies concerning maternal and fetal complications and explores mechanistic investigations that reveal the underlying pathophysiology.

Evaluation of Conventional and Combined Doppler Parameters in Preeclampsia: Diagnostic and Prognostic Insights.

Background: The aim of this study was to examine the relationship between conventional and novel Doppler parameters, including cerebroplacental ratio (CPR), cerebral-placental-uterine ratio (CPUR), umbilical-to-cerebral ratio (UCR), and amniotic-to-umbilical-cerebral ratio (AUCR), with the diagnosis of preeclampsia (PE) and adverse neonatal outcomes in PE cases. Methods: This prospective case-control study was conducted at the Ankara Etlik City Hospital Perinatology Clinic between November 2023 and May 2024. The study population was divided into two groups: Group 1, consisting of 74 patients diagnosed with preeclampsia, and Group 2, consisting of 80 healthy control patients. Composite adverse perinatal outcomes (CANOs) include presence of at least one adverse outcome: 5th-minute APGAR score < 7, transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), need for continuous positive airway pressure (CPAP), need for mechanical ventilation, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia, need for phototherapy, intraventricular hemorrhage (IVH), and neonatal sepsis. Results: The CPR, CPUR, and AUCR were significantly lower in the PE group compared to the control group, while the UCR was notably higher in the PE group. Among the combined ratios, the CPUR exhibited the highest diagnostic performance for both PE diagnosis and the prediction of CANOs. Additionally, while the UCR, CPR, and AUCR were significant for PE diagnosis, only AUCR demonstrated a significant association with the prediction of CANOs. Conclusions: Combined Doppler parameters, especially CPUR and AUCR, offer valuable insights into diagnosing PE and predicting CANOs. CPUR demonstrated the highest diagnostic accuracy, underscoring its potential utility in clinical settings.

Risk-Prioritised Versus Universal Medical Nutrition Therapy for Gestational Diabetes: A Retrospective Observational Study.

The optimal application of medical nutrition therapy (MNT) in treating gestational diabetes remains uncertain. MNT involves individualised nutrition assessment and counselling, which is labour-intensive and is not the sole type of intervention offered by clinical dietitians. To determine whether pregnancy outcomes differed for individuals with gestational diabetes who were offered MNT on a risk-prioritised (RP) versus universal basis. Observational data from two cohorts of individuals who were offered MNT only if they met the high-risk criteria following general group-based dietary education (RP1, n = 369; RP2, n = 446) were compared with a baseline cohort who were universally offered at least one MNT consultation (UM, n = 649). The RP1 cohort were seen during community-wide COVID-19 restrictions in 2021, while RP2 were seen after restrictions had lifted in 2022. Furthermore, the RP approach primarily utilised telemedicine, while the UM approach was delivered in person. MNT consultations halved under the RP approach (59 vs. 119 sessions per 100 diagnoses for RP2 vs. UM) and saved more than 20 h of dietitian time per 100 diagnoses (95 vs. 73 h for RP2 vs. UM). No significant increases were observed (p < 0.05) for any pregnancy outcomes in the RP cohorts compared with the UM cohort, including usage of diabetes medications, maternal weight gain below and above target, early deliveries, induced deliveries, emergency caesarean sections, large- and small-for-gestational-age (SGA) infants, infant macrosomia, neonatal hypoglycaemia and neonatal intensive care admissions. The use of both basal insulin (27% vs. 33%, OR 0.62, 95% CI 0.46 to 0.84) and metformin (6% vs. 10%, OR 0.52, 95% CI 0.31 to 0.88) was lower in the RP1 cohort during pandemic restrictions compared with the UM cohort; however, these differences were not retained in the RP2 cohort. Additionally, there were fewer SGA infants under the RP approach, particularly for the RP2 cohort (6% vs. 11% for RP2 vs. UM, OR 0.55, 95% CI 0.34 to 0.89). Risk-prioritised MNT was a more efficient dietetic service approach to gestational diabetes than the universal MNT model, with comparable pregnancy outcomes. Similar approaches may represent a strategic way to address sustainable health service planning amidst the rising global prevalence of this condition. However, further research is needed to investigate consumer perspectives, wider service impacts and post-partum maternal and child health outcomes.

Re-evaluating large for gestational age: differential effects on perinatal outcomes in term and premature births.

Pregnancies with large-for-gestational-age (LGA) fetuses are associated with increased risks of various adverse perinatal outcomes. While existing research primarily focuses on term neonates, less is known about preterm neonates. This study aims to explore the risks of adverse maternal and neonatal perinatal outcomes associated with LGA in term neonates and neonates with different degrees of prematurity, compared to appropriate-for-gestational-age (AGA) neonates. Using the Birth Reporting Databases (2007-2018) linked to Taiwan's National Health Insurance Research Database, we conducted a retrospective nationwide cohort study of singleton neonates delivered between 24 and 42 weeks of gestation. Based on gestational age at delivery, the enrolled neonates were classified into term (37-42 weeks of gestation), late preterm (34-36 weeks of gestation), moderate preterm (32-33 weeks of gestation), very preterm (28-31 weeks of gestation), and extremely preterm (24-27 weeks of gestation). LGA was defined by the 2013 World Health Organization (WHO) growth standard and the Taiwan growth standard. Perinatal outcomes were compared between LGA and AGA neonates across different gestational age groups. Among the 1,602,638 neonates, 44,359 were classified as LGA by the 2013 WHO growth standard. Compared to AGA neonates, LGA neonates in term and late preterm groups exhibited higher risks of primary cesarean section, prolonged labor, neonatal hypoglycemia, birth trauma, hypoxic ischemic encephalopathy, jaundice needing phototherapy, respiratory distress, neonatal intensive care unit (NICU) admission, newborn sepsis, and fetal death. However, most of these risks were not increased in moderate, very, and extremely preterm groups. Conversely, being LGA was associated with lower risks of primary cesarean section (very preterm group), jaundice needing phototherapy (moderate and very preterm groups), respiratory distress (moderate and very preterm groups), NICU admission (moderate and very preterm groups), newborn sepsis (very preterm group), retinopathy of prematurity (late, moderate, and very preterm groups), and bronchopulmonary dysplasia (very preterm group). These findings remained consistent when the Taiwan growth standard was applied. Being LGA is associated with increased risks of perinatal complications in term and late preterm neonates, but not in earlier preterm groups. These findings underscore the importance of tailoring management strategies for LGA neonates to consider different degrees of prematurity.

Subtypes of Gestational Diabetes Mellitus Are Differentially Associated With Newborn and Childhood Metabolic Outcomes.

Subtypes of gestational diabetes mellitus (GDM) based on insulin sensitivity and secretion have been described. We addressed the hypothesis that GDM subtypes are differentially associated with newborn and child anthropometric and glycemic outcomes. Newborn and child (age 11-14 years) outcomes were examined in 7,970 and 4,160 mother-offspring dyads, respectively, who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study (HAPO) and Follow-Up Study. GDM was classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity), insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion), or mixed-defect GDM (both <25th percentile). Regression models for newborn and child outcomes included adjustment for field center, maternal BMI, and other pregnancy covariates. Child models also included adjustment for child age, sex, and family history of diabetes. Compared with mothers with normal glucose tolerance, all three GDM subtypes were associated with birth weight and sum of skinfolds >90th percentile. Insulin-resistant and mixed-defect GDM were associated with higher risk of cord C-peptide levels >90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia and childhood obesity (odds ratio [OR] 1.53, 95% CI 1.127-2.08). The risk of child-impaired glucose tolerance was higher with insulin-resistant (OR 2.21, 95% CI 1.50-3.25) and mixed-defect GDM (OR 3.01, 95% CI 1.47-6.19). GDM subtypes are differentially associated with newborn and childhood outcomes. Better characterizing individuals with GDM could help identify at-risk offspring to offer targeted, preventative interventions early in life.

Prevalence, Morbidity Pattern and Outcome of HIV Exposed Infants admitted into The Special Care Baby Unit of Rivers State University Teaching Hospital, Nigeria

Background: HIV/AIDS remains a major cause of morbidity and mortality in the paediatric age group including the neonatal age. Materials and Methods: A prospective study carried out from January 5th 2021 to 4th December, 2023 in the neonatal unit of the Rivers State University Teaching Hospital. Results: Of 1412 neonates admitted, 48 were HIV exposed with prevalence rate of 3.4%, M:F ratio of 1:1.2 and mean birth weight of 2.82 ± 0.93kg. Most mothers were &gt;30years, 31(64.6%) with secondary level of education 28(58.3%). Majority commenced antenatal care in the 1st trimester 26(54.7%) and delivered via emergency Caesarean section 24(50.0%). Most maternal HIV status was known before index pregnancy 28(58.2%) and commenced HAART 29(67.4%). Most baby’s feeding option was exclusive breast feeding (75.0%) while mixed feeding was 6.3%. Nevirapine was given to 31(64.6%) infants and nevirapine/zidovudine to 17(35.4%). The commonest morbidities were probable neonatal sepsis 27(58.7%), hypoglycaemia 13(28.3%), neonatal jaundice 9(19.6%) and perinatal asphyxia 9(19.6%). There was mortality rate of 4.2% with HIV seropositivity rate at 6-8 weeks being 10.9%. Mothers’ level of education and occupation were significantly associated with HIV seropositivity rate (P=0.041, 0.049) whereas the pattern of morbidity had no significant association with the infants seropositivity rate. Conclusion: The prevalence of HIV exposed infants admitted was 3.4% with M:F ratio of 1:1.2. The commonest morbidities were probable neonatal sepsis, hypoglycaemia, neonatal jaundice and perinatal asphyxia. There was a mortality rate of 4.2% with high infants seropositivity rate of 10.9%. This therefore calls for an intensification of the PMTCT program. Keywords: HIV exposed infants; Prevalence; Morbidity; Outcome

Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes

Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age. Netherlands Trial Registry Identifier: NTR6134.

CROSS-SECTIONAL STUDY ON THE PREVALENCE OF GESTATIONAL DIABETES AND ITS MANAGEMENT PRACTICES

Background: Gestational diabetes mellitus (GDM) is a prevalent pregnancy-related condition characterized by glucose intolerance, increasing maternal and neonatal risks. Globally, GDM contributes significantly to adverse outcomes, including macrosomia, preeclampsia, and neonatal hypoglycemia. Early identification and management are critical to reducing these complications. However, limited knowledge, attitudes, and practices (KAP) among women with GDM and regional disparities in healthcare access often lead to suboptimal outcomes, particularly in resource-limited settings like Pakistan. Objective: To assess the prevalence of GDM and evaluate the knowledge, attitudes, and practices (KAP) regarding its management among affected women in Karachi, Pakistan. Methods: This cross-sectional study was conducted in selected hospitals in Karachi, Pakistan, from July 2023 to January 2024. A total of 189 participants diagnosed with GDM at 24–34 weeks of gestation were recruited using consecutive sampling. Data were collected using a structured, pre-validated questionnaire, which assessed demographic details, clinical history, and KAP scores. Statistical analyses, including Spearman correlation and multivariate logistic regression, were used to evaluate associations between knowledge, attitudes, and practices. Ethical approval was obtained from institutional review boards. Results: The mean age of participants was 30.4 ± 4.2 years, with 57% (n=108) reporting a family history of diabetes. The average BMI was 28.7 ± 3.5 kg/m², with 77% categorized as overweight or obese. Mean KAP scores were 10.9 ± 2.8 (knowledge), 32.8 ± 4.5 (attitude), and 12.4 ± 2.9 (practice), with 68% (n=129), 73% (n=138), and 65% (n=123) achieving good scores, respectively. Knowledge and attitude scores were positively correlated (r=0.329, p&lt;0.001). Higher knowledge scores were independently associated with better practices (OR: 1.145, 95% CI: 1.051–1.247, p=0.002). Conclusion: This study highlights moderate knowledge and practices but strong attitudes toward GDM management among women in Karachi. Educational interventions are essential to improve self-management and healthcare outcomes.

Pre-gestational diabetes in a young woman with a pathogenic INSR missense mutation, p.(Met1180Lys).

Heterozygous insulin receptor (INSR) mutations cause type A insulin resistance (IR), associated with a phenotype of IR; hyperandrogenism, oligomenorrhoea and acanthosis nigricans in the absence of obesity or lipoatrophy. The phenotype is variable, ranging from neonatal hyperinsulinaemic hypoglycaemia to fasting or post-prandial hypoglycaemia in adults to diabetes. We report a 29-year-old woman presenting at 13 weeks gestation in her second pregnancy. Diabetes was diagnosed at 13-years-old following presentation with lethargy and polyuria and she was treated with metformin 500 mg po bd. She also had polycystic ovarian syndrome, hypothyroidism and epilepsy. Metformin was changed to insulin with good glycaemic control throughout pregnancy. She delivered a 3.95 kg male infant at 39 weeks gestation without neonatal hypoglycaemia. At 18 months post-partum, her body mass index was 26.3 kg/m2, with no evidence of acanthosis nigricans or features of lipodystrophy. As her sister was also diagnosed with diabetes at 13-years-old, next-generation sequencing was performed for known maturity onset diabetes of the young (MODY) genes and a p.(Met1180Lys) mutation in the INSR gene was detected. She reported nocturnal hypoglycaemia and a 5-h oral glucose tolerance test revealed post-prandial hyperinsulinaemic hypoglycaemia at 210 min. Her subsequent pregnancy was spontaneously treated with metformin 500 mg po od from 8 to 25 weeks gestation and discontinued due to intrauterine growth restriction. She delivered a 1.8 kg female infant at 34 plus 3 weeks gestation (25th centile) via elective caesarean section. The infant had transient neonatal hypoglycaemia for two days. Post-partum, she remains diet controlled, with a haemoglobin A1c of 32 mmol/mol. This case highlights the importance of genetic testing to establish optimal diabetes treatment. This case highlights the less severe phenotype of IR in a subject with an INSR p.Met1180Lys mutation. It demonstrates the existence of symptomatic post-prandial hypoglycaemia in an adult subject associated with hyperinsulinaemia. This case highlights the importance of genetic testing to establish diagnosis and allows for precision medicine. The role of metformin use in Type A-IR and pregnancy needs to be established.

A retrospective cross-sectional study on the prevalence of adverse perinatal outcomes and its associated factors in fetuses with late-onset fetal growth restriction

Late-onset fetal growth restriction (FGR) has a possibility of urgent fetal deterioration before labor, which contributes to late-pregnancy mortality, intrapartum fetal distress, and neonatal acidosis. This study was conducted to evaluate the prevalence of adverse perinatal outcomes (APO) and identify factors associated with APO in fetuses with late-onset FGR. This was a retrospective cross-sectional study of singleton pregnancies diagnosed with late-onset FGR, enrolled in Tu Du Hospital from 4/2022 to 12/2022. Late-onset FGR was defined according to the Delphi consensus. Databases of Doppler parameters and APO were recorded. Of 101 pregnancies in the study, APO occurred in 21 cases (20.8%). The need for admission to the neonatal intensive care unit, the mean overall length of hospital stay, neonatal resuscitation requiring mechanical ventilation, neonatal jaundice requiring phototherapy, and neonatal hypoglycemia were recorded, respectively, in 21 (20.8%), 6.67 days, 11 (10.9%), and 2 (2%) cases, while no case of perinatal death and 5-min Apgar score&lt;7 was reported in the study. In the prediction of APO, there was a significant contribution from cerebroplacental ratio (CPR)&lt;5 percentile (adjusted OR (aOR)=4.76, 95% confidence interval [CI] 1.07–21.11, p=0.04), EFW&lt;3 percentile (aOR=3.22, 95% CI 1.01–10.27, p=0.049) and gestational age at delivery (aOR=0.35, 95% CI 0.18–0.65, p=0.001). In our research, the prevalence of APO is 20.8%. CPR&lt;5 percentile, severe late-onset FGR, and gestational age at delivery are independently statistically associated with APO in pregnancies with late-onset FGR.

A Case Study on Neurological Outcome in Persistent Neonatal Hypoglycemia in Upper Middle-Income Country

In Indonesia, comprehensive management and monitoring of persistent neonatal hypoglycemia, is rarely reported. Despite the fact that there are studies highlighting the risk of neurodevelopmental disorders in neonates with hypoglycemia, there seems to be limited comprehensive case reports detailing both the early diagnosis and the long-term growth and development monitoring in these neonates. A unique case report of a 10-day-old male baby, born at a term weeks gestation via caesarean section, diagnosed with persistent hypoglycemia and suspect of hyperinsulinemia is presented in this study. At birth, the neonate exhibited hypoglycemia with a blood glucose level of 25 mg/dL, accompanied by a one-minute seizure characterized by upward gaze and stiffening of the extremities. The neonate cried after seizure and there was no loss of consciousness and was admitted to the NICU due to worsening respiratory distress. Based on the thoracic X-ray examination, he was diagnosed with transient tachypnea of newborn (TTN). Blood glucose levels were monitored every four hours, and tests for cortisol, thyroid and growth hormone and routine urinalysis were planned. Total parenteral nutrition (TPN) were given with intravenous antibiotics. At 6months of age, the infant was diagnosed with intellectual disability by the growth and development social pediatric unit. At 7 months, the infant began undergoing physiotherapy. This case was followed for 7 months in total and the findings highlight the challenges in managing neonatal persistent hypoglycemia and the potential long-term developmental implications in neonates with early-life hypoglycemia, emphasizing the need for continual growth and development monitoring.

FETAL OUTCOME IN PRE-EXISTING TYPE 2 DIABETIC MOTHERS

Diabetes mellitus is one of the most common medical complications of pregnancy at present. Pre-existing diabetes mellitus is associated with morbidity in the mother and offspring, as well as infant mortality. Objective: To determine the frequency of fetal outcomes in pre-existing type 2 diabetic mothers at Shaikh Zaid Women Hospital. Methods: This Cross-sectional study was conducted at the Department of Obstetrics and Gynecology, The Shaikh Zaid Women Hospital from December 2023 to May 2024. Data were collected through a non-probability consecutive sampling technique. Gynaecologist sonographers performed clinical assessment and transvaginal pelvic ultrasound. Results: Data were collected from 168 patients. Preterm delivery was the most frequent outcome, observed in 60 cases (35.7%), followed by neonatal hypoglycemia in 50 cases (29.8%) and respiratory distress in 35 cases (20.8%). Other notable complications included low birth weight (16.7%), congenital anomalies (11.3%), and macrosomia (10.7%). Neonatal death was reported in 3 cases (1.8%), and a low Apgar score was recorded in 15 cases (8.9%). The mean maternal age was 31.4 ± 4.8 years, with a median age of 31 (IQR: 28–35). The average HbA1c level was 6.8 ± 0.4%, with a median of 6.7% (IQR: 6.5–7.1), indicating generally well-controlled glycemic levels. Conclusion: Pre-existing type 2 diabetes mellitus is associated with a high frequency of adverse fetal outcomes, including preterm delivery, neonatal hypoglycemia, and respiratory distress. Optimal glycemic control and targeted antenatal care are essential to mitigate these risks and improve neonatal outcomes.