Neonatal Hypoglycemia Research Articles

Presence of mitochondrial dysfunction in a case of Fanconi syndrome with normoglycemic MODY1.

Maturity-onset diabetes of the young 1 (MODY1) is characterized by macrosomia and transient hypoglycemia in neonates, in addition to diabetes mellitus (DM). Only patients with MODY1 harboring a pathogenic variant (c.187C > T; p.R63W) in HNF4A are sure to develop Fanconi syndrome (FS). Here we report the successful diagnosis of MODY1 in a patient harboring p.R63W before confirmation of DM-related hyperglycemia after being alerted to the presence of abnormal mitochondria in a kidney-biopsy specimen revealed by electron microscopy. The patient was born at 39weeks of gestation with macrosomia, elevated levels of liver enzymes, and transient hypoglycemia. At three years of age, proteinuria was found by chance, and further laboratory investigations revealed metabolic acidosis, mild renal dysfunction, hypouricemia, proteinuria, aminoaciduria, and glycosuria. On this basis, we diagnosed the patient as having FS and performed percutaneous renal biopsy. Light microscopy revealed no evidence of proximal tubule disorder, but electron microscopy demonstrated mitochondria with disordered cristae in glomerular podocytes and giant mitochondria in proximal tubules. Mitochondrial nephropathy was suspected, and skin fibroblasts from the patient grown on galactose medium showed decreased oxygen consumption suggestive of mitochondrial dysfunction. Therefore, genetic testing was performed and a pathogenic variant (c.187C > T; p.R63W) in HNF4A was detected. Mitochondrial dysfunction in a Drosophila and murine model of patients with both MODY1 and FS has already been reported, and we detected it in this human MODY1/FS patient on the basis of functional tests and imaging. We believe mitochondrial dysfunction may be involved in the pathogenesis of MODY1/FS.

Persistent Hypoglycemia in Premature, Small for Term, and Low Birth Weight Neonates from Mothers with a History of Severe Preeclampsia

Background: Neonatal hypoglycemia is a metabolic problem that is often found in the NICU and is one of the causes of permanent brain damage in infants. The diagnosis of persistent hypoglycemia and its causes are still controversial. Case: A male baby was born to a mother with severe preeclampsia at 36 weeks of gestation, with a birth weight of 1600 grams. At 1 hour of age, he experienced hypoglycemia that lasted more than 72 hours with the lowest blood sugar of 18 mg/dL, and experienced hyperkalemia (potassium level 6.1 mmol/L). The baby is diagnosed as persistent hypoglycemia. The clinical condition improved after being given dextrose and dexamethasone, and was discharged in stable condition. Conclusion: Management of persistent hypoglycemia depends on the cause. Diagnosis refers to risk factors before or after birth.

External Validation of the PeRSonal Gestational Diabetes Model for Predicting Adverse Pregnancy Outcomes in Women with Gestational Diabetes: A Retrospective Cohort Study in a Tertiary Hospital in Thailand

Objective: This study aimed to validate the PeRSonal Gestational Diabetes (GDM) model with two-step glucose tolerance diagnostic criteria.Material and Methods: A retrospective cohort study was conducted on participants having delivered with GDM diagnosis in a tertiary hospital; from October 1, 2020, until September 30, 2022. The main outcome was a composite of maternal and perinatal adverse pregnancy complications. Model validation evaluated the predictors and calculated risk by using a two-step glucose tolerance test in the PeRSonal model formula. Model performance was analyzed for discrimination, calibration, and overall performance. Results: This study analyzed 685 from the initial 764 participants with GDM, with 218 (31.8%) developing adverse pregnancy outcomes. The most frequent adverse outcomes were hypertensive disorders in pregnancy 132 (19.3%) and neonatal hypoglycemia 91 (13.3%). This validation achieved an area under the curve (AUC) of 0.70 (95% confidence interval (CI) 0.65 to 0.74), calibration-in-the-large of 0.17, a calibration slope of 1.34, and a Brier score of 0.20, respectively. The cut-off clinical risk probability of 27.5% can predict adverse outcomes with a sensitivity of 67.3%, specificity of 63.8%, a positive predictive value (PPV) of 46.7%, and a negative predictive value (NPV) of 80.5%. Conclusion: The PeRSonal model maintains its predictive effectiveness in two-step glucose tolerance diagnostic criteria.

Neurodevelopmental Outcome in Infants of Gestational Diabetic Mother in a Tertiary Care Hospital, Dhaka, Bangladesh

Background: Diabetes Mellitus (DM) is one of the most common metabolic complications of pregnancy, with negative influences on maternal and fetal health. Infants of Diabetic Mothers (IDMs) are prone to develop both early and late complications. Evidences shows that diabetes in pregnancy have strong association with long-term adverse effects on brain development in babies born to mothers with gestational diabetes mellitus. Very few studies were done in this subcontinent regarding association of gestational diabetes mellitus and infant’s neurodevelopmental outcome. This study will help to find out this associations and thus to reduce poor neurodevelopmental outcome in infants of diabetic mothers by early detection and providing proper early childhood stimulation. Objective: To assess the neurodevelopmental outcome of infants born to mother with gestational diabetes mellitus. Methodology: This prospective observational study was conducted in the department of Neonatology and Institute of Pediatric Neurodisorder and Autism (IPNA), BSMMU, from March 2022 to September 2023. Neonates (N= 52) born at or after 34 weeks of gestation and born to gestational diabetic mother were enrolled in this study. Consent was taken from guardians. The newborns fulfilling the inclusion criteria were followed up for neurodevelopmental assessment at their 9 months of age by clinical psychologists assigned from Institute of Pediatric Neurodisorder and Autism (IPNA), BSMMU, who were blinded about infant’s diagnosis. Bayley scales of infant and toddler development (BSID III) was used for developmental assessment. In the Bayley III, cognitive development, expressive and receptive language and fine and gross motor development all were evaluated at 9 months of age. All data were recorded in a preformed questionnaire and analyzed by Statistical Package for Social Sciences (SPSS), version 25. Results: According to inclusion and exclusion criteria 58 newborn were enrolled and their blood samples were sent at 24 to 48 hours of age to see the laboratory parameters of metabolic and hematological profile. Among them 6 patients lost to follow up, so 52 infants were followed up for neurodevelopmental outcome at 9 months of age. Among the baseline characteristics of mother and neonate 48% mother needed drugs for glycemic control, while others were on dietary modification and 75% of the mothers had good glycemic control. Most of the neonate were born at term and were age appropriate, 18 patients needed NICU admission. Among the neonatal laboratory parameters hyperbilirubinemia was most common (30.8%) and hypoglycemia was second most common found in 15.4% of newborns. The most common morbidity was sepsis (17.3%). Overall adverse neurodevelopmental outcome was found among 14 (26.9%) neonate and 38 (73.1%) neonates had favorable outcome. Use of drugs and poor maternal glycemic control were found statistically significant in between adverse and favorable groups. (p-value- 0.041 and 0.000). Among the neonatal clinical parameters only hypoglycemia was found statistically significant in between these two groups. (p-value- 0.014) Multivariate logistic regression among these predictive factors showed only maternal poor glycemic control was significantly associated with adverse neurodevelopmental outcome (p-value=0.001). Conclusion: Maternal gestational diabetes can adversely affect on their infants neurodevelopment. Among the adverse outcome of three domains language delay was most common. Neonatal hypoglycemia, maternal poor glycemic control and use of drugs for GDM are significant predictors of adverse neurodevelopmental outcome in infants of gestational diabetic mother. Among them maternal poor glycemic control was significantly associated with adverse neurodevelopmental outcome.

Perinatal and neonatal outcomes in gestational diabetes: The importance of the number of abnormal values in an oral glucose tolerance test.

Gestational diabetes mellitus (GDM) is defined by one or more abnormal values in an oral glucose tolerance test (OGTT). The significance/importance of the number of abnormal values in relation to adverse perinatal and neonatal outcomes is unclear. We assessed the association of these outcomes with the number of abnormal glucose values in a 2-h 75 g OGTT in a large register-based cohort. This sub-study of the Finnish Gestational Diabetes Study was based on the Finnish Medical Birth Register 2009 supplemented with OGTT laboratory data of 4869 pregnant women from six Finnish hospitals. The diagnostic cut-offs in OGTT according to the Finnish guidelines for plasma samples were ≥5.3 mmol/L (fasting), ≥10.0 mmol/L 1 h or ≥8.6 mmol/L 2 h after the glucose load. As per the guidelines, women with one or several abnormal OGTT values received diet and lifestyle counseling in the primary care, self-monitored their glucose values and received pharmacological therapy as needed. Women with GDM were categorized according to the number of abnormal glucose values. The primary outcomes, composites of adverse perinatal (pre-eclampsia, preterm delivery, macrosomia or primary cesarean section) and neonatal outcomes (birth trauma, neonatal hypoglycemia, hyperbilirubinemia or stillbirth/perinatal mortality), were analyzed by logistic regression adjusted for maternal age, pre-pregnancy body mass index, parity, socio-economic status and smoking. Of all the women, 877 (18.0%) had one, 278 (5.7%) two and 79 (1.6%) three abnormal OGTT values, while 3635 (74.7%) women were normoglycemic. Women with at least two abnormal OGTT values had higher proportions of adverse perinatal composite (35.0% vs. 27.5%, adjusted odds ratio 1.36; 95% confidence interval 1.03-1.81) and neonatal composite outcomes (31.1% vs. 18.9%, adjusted odds ratio 1.88; 95% confidence interval 1.40-2.52) compared to women with one abnormal value. The risks of delivery induction and neonatal hypoglycemia were increased regardless of the number of abnormal values when compared with normoglycemic women. The risk of adverse perinatal and neonatal outcomes is significantly higher in women with two or more abnormal OGTT values than in those with one abnormal value.

Polycystic ovary syndrome and gestational diabetes mellitus association to pregnancy outcomes: A national register-based cohort study.

It is well known that both women with polycystic ovary syndrome (PCOS) and women with gestational diabetes mellitus (GDM) have increased risks of adverse pregnancy outcomes, but little is known whether the combination of these two conditions exacerbates the risks. We explored risk estimates for adverse pregnancy outcomes in women with either PCOS or GDM and the combination of both PCOS and GDM. Nationwide register-based historical cohort study in Sweden including women who gave birth to singleton infants during 1997-2015 (N = 281 806). The risks of adverse pregnancy outcomes were estimated for women exposed for PCOS-only (n = 40 272), GDM-only (n = 2236), both PCOS and GDM (n = 1036) using multivariable logistic regression analyses. Risks were expressed as odds ratios with 95% confidence intervals (CIs) and adjusted for maternal characteristics, including maternal BMI. Women with neither PCOS nor GDM served as control group. Maternal outcomes were gestational hypertension, preeclampsia, postpartum hemorrhage, and obstetric anal sphincter injury. Neonatal outcomes were preterm birth, stillbirth, shoulder dystocia, born small or large for gestational age, macrosomia, low Apgar score, infant birth trauma, cerebral impact of the infant, neonatal hypoglycemia, meconium aspiration syndrome and respiratory distress. Based on non-significant PCOS by GDM interaction analyses, we found no evidence that having PCOS adds any extra risk beyond that of having GDM for maternal and neonatal outcomes. For example, the adjusted odds ratio for preeclampsia in women with PCOS-only were 1.18 (95% CI 1.11-1.26), for GDM-only 1.77 (95% CI 1.45-2.15), and for women with PCOS and GDM 1.86 (95% CI 1.46-2.36). Corresponding adjusted odds ratio for preterm birth in women with PCOS-only were 1.34 (95% CI 1.28-1.41), GDM-only 1.64 (95% CI 1.39-1.93), and for women with PCOS and GDM 2.08 (95% CI 1.67-2.58). Women with PCOS had an increased risk of stillbirth compared with the control group (aOR 1.52, 95% CI 1.29-1.80), whereas no increased risk was noted in women with GDM (aOR 0.58, 95% CI 0.24-1.39). The combination of PCOS and GDM adds no extra risk beyond that of having GDM alone, for a number of maternal and neonatal outcomes. Nevertheless, PCOS is still an unrecognized risk factor in pregnancy, exemplified by the increased risk of stillbirth.

Neonatal hypoglycemia: A review with focus on practical challenges and recent updates on management

At birth, a neonate undergoes a transition from the continuous maternal supply of glucose to a variable and intermittent oral glucose intake, which is regulated by the interplay of hormones and metabolic enzyme induction. Because low plasma glucose concentrations are common in the neonatal period, it may be difficult to identify those who have pathologic hypoglycemia. Hence, it is important to formally evaluate such babies by drawing critical samples. Here, we present two cases of neonatal hypoglycemia where the presentation had some similarities, but the comprehensive evaluation revealed a varied etiological spectrum necessitating lifelong management. Through these case studies, authors discuss practical challenges in the diagnosis, management, and follow-up of neonates with endocrine causes of hypoglycemia.

Metformin in gestational diabetes: physiological actions and clinical applications.

Metformin is an effective oral hypoglycaemic agent used in the treatment of type 2 diabetes mellitus; however, its use in pregnancy for the treatment of gestational diabetes mellitus (GDM) remains controversial owing to concerns around safety and efficacy. This comprehensive review outlines the physiological metabolic functions of metformin and synthesizes existing literature and key knowledge gaps pertaining to the use of metformin in pregnancy across various end points in women with GDM. On the basis of current evidence, metformin reduces gestational weight gain, neonatal hypoglycaemia and macrosomia and increases insulin sensitivity. However, considerable heterogeneity between existing studies and the grouping of aggregate and often inharmonious data within meta-analyses has led to disparate findings regarding the efficacy of metformin in treating hyperglycaemia in GDM. Innovative analytical approaches with stratification by individual-level characteristics (for example, obesity, ethnicity, GDM severity and so on) and treatment regimens (diagnostic criteria, treatment timing and follow-up duration) are needed to establish efficacy across a range of end points and to identify which, if any, subgroups might benefit from metformin treatment during pregnancy.

A double‐blind, randomized, placebo‐controlled trial of melatonin as an adjuvant agent for induction of labor: The MILO trial

AbstractIntroductionMelatonin has been suggested to have a biological role in the onset and progress of labor. We tested the hypothesis that the addition of melatonin during an induction of labor will reduce the need for a cesarean birth.Material and MethodsThis trial underwent protocol amendments that are detailed in the main text of the article. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000311459). At a multi‐center health service including secondary and tertiary obstetric hospitals, we performed a randomized, double‐blind, placebo‐controlled trial in women with a singleton cephalic pregnancy, free of significant maternal or perinatal complications who were undergoing induction of labor (with or without cervical ripening). Women were randomized to 10 mg melatonin vs placebo, with cervical ripening as required, and then 6‐h during their induction of labor to a maximum of four doses or until birth. The primary outcome was cesarean birth. Secondary outcomes included labor, maternal, and neonatal outcomes. Data were analyzed using intention to treat. Sub‐group analyses based on mode of ripening and parity were also performed.ResultsBetween 2019 and 2021 we randomized 189 women (103 to melatonin and 86 to placebo). The study was prematurely terminated due to logistical complications resulting from the COVID‐19 pandemic. Cesarean rates were 28/103 (27.2%) in the melatonin group versus 20/84 (23.3%) in the placebo group (RR 1.17 95% CI 0.71–1.92). There were no significant differences in rate of cesarean birth between the melatonin and placebo groups for failure to progress (13.4% and 9.3%, respectively, RR 1.46; 95% CI 0.64–3.32) or suspected fetal distress (10.7% and 10.5%, respectively, RR 1.02; 95% CI 0.44–2.34). The melatonin group had significantly lower rates of spontaneous vaginal birth within 24 h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50–0.98). The rates of secondary outcomes such as total length of labor, rate of postpartum hemorrhage, and instrumental birth were comparable. Babies born in the melatonin group were more likely to need admission to the special care nursery, namely for hypoglycemic monitoring (18.5% vs. 8.1% RR 2.26; 95% CI 1.00–5.10).ConclusionsIn women undergoing induction of labor, melatonin does not reduce the cesarean section rate. Melatonin use intrapartum may also be associated with neonatal hypoglycemia.

Gestational Diabetes : A Cross-Section of Factors and Complications in Mothers and Newborns in Southern Morocco

By way of introduction, the prevalence of gestational diabetes varies between 1% and 14%, in Morocco, a single study conducted in Dakhla in southern Morocco in 2019, estimates that the prevalence of GD is 7.7% in accordance with the recommendations of the American Diabetes Association, hence the need to explore the epidemiological profile in southern Morocco.  Methodology:- A cross-sectional descriptive analytical correlational epidemiological survey of 202 pregnant women during the period 2021-2022, conducted at the Dakhla regional hospital centre, which attempts to describe the individual, biological and gynecological-obstetric risk factors in pregnant women with gestational diabetes. As well as maternal and neonatal complications. The study also analyses the effect of hospital performance on the management of parturients.  Results:- The prevalence of GD is high in the age group [35,41] and over 42 years, mainly among illiterate. Several risk factors have been identified for GD : age, high preconceptional BMI, low level of education, polycystic syndrome, history of urinary infection, positive vaginal swab for Streptococcus B, and complications for mothers and newborns revolving around Dystocic delivery, macrosomia and hypoglycaemia in newborns. There is also retinopathy in premature babies due to candida albicans and early bacterial infection due to GSB in full- term newborns.

Are toddlers with neurosensory impairment more difficult to follow up? A secondary analysis of the hPOD follow-up study

ObjectiveTo describe strategies used to maximise follow-up after a neonatal randomised trial, how these differed for families of different ethnicity, socioeconomic status and urban versus rural residence and investigate relationships...

Predicting the Risk of Adverse Neonatal Outcomes in Women With Insulin-Treated Diabetes: Is It Time for a Pregnancy-Specific Glycemic Risk Index (GRI)?

The Glycemia Risk Index (GRI) describes the quality of glycemic control, emphasizing extreme hypoglycemia and hyperglycemia more than less extreme values. However, a pregnancy-specific GRI (pGRI), tailored to the tighter target glucose range required during pregnancy, has not been established. We retrospectively evaluated clinical, metabolic, and Continuous Glucose Monitoring (CGM) data across pregnancy in women with insulin-treated diabetes, managed between September 2021 and March 2024 at the University Hospital of Pisa. First and second levels of hyperglycemia (TAR1: 140-180 mg/dL, TAR2: >180 mg/dL) and hypoglycemia (TBR1: 63-54 mg/dL, TBR2: <54 mg/dL) were used to calculate the pGRI at each trimester. Logistic regression analysis investigated the association between pGRI and risk of at least one adverse neonatal outcome (among preterm delivery, macrosomia, large for gestational age, small for gestational age, neonatal hypoglycemia, neonatal jaundice, and neonatal intensive care unit admission). Of 45 pregnant women, 25 (56%) experienced at least one adverse neonatal outcome. In the third trimester, women with adverse outcomes had significantly higher total TAR (26 [12-32]% vs 10 [4-23]%, P = .018) and lower TIR (71 [64-83]% vs 88 [75-92]%, P = .007). Specifically, the difference was notable in TAR2 (6 [2-15]% vs 1 [0-4]%, P = .004), whereas TAR1 was comparable between the 2 groups. Accordingly, third trimester pGRI was higher in women with adverse neonatal outcomes (38 [18-49]% vs 18 [10-31]%, P = .013) and, at logistic regression, slightly but significantly increased the risk of adverse neonatal outcomes (1.044 [1.004-1.086], P = .024). Pregnant women with insulin-treated diabetes reporting adverse neonatal outcomes spent more time in hyperglycemia, particularly in extreme hyperglycemia. Therefore, the level of hyperglycemia should always be assessed during pregnancy. The pGRI, emphasizing extreme hyperglycemia, may be a novel comprehensive tool for assessing the risk of adverse neonatal outcomes.

Predicting Neonatal Hypoglycemia Using AI Neural Networks in Infants from Mothers with Gestational Diabetes Mellitus.

BACKGROUND This study aimed to develop a predictive model for the association between maternal and neonatal anthropometric data and neonatal hypoglycemia based on data from mothers with gestational diabetes mellitus (GDM) and their neonates. MATERIAL AND METHODS We included 106 pregnant women with GDM (based on the World Health Organization International Association of Diabetes and Pregnancy Study Groups) and their neonates. Neonatal hypoglycemia was defined as a threshold of 2.5 mmol/L. Neonatal blood glucose levels were performed at 0, 0.5, 1, 3, and 24 h after birth. An artificial neural network (ANN) and recurrent neural network (RNN) were developed to predict the neonate blood concentrations and investigate the relative contribution of maternal and neonate clinical variables to neonatal hypoglycemia. RESULTS Of 106 mothers with GDM, 85% had obesity, and 78% had vaginal deliveries, with neonates averaging a birth weight of 3335.83 g. The ANN model, based on the clinical data from mothers and neonates, predicted blood glucose levels with a high degree of accuracy, achieving a coefficient of determination of 0.869 and a root mean square error (RMSE) of 0.274. Neonatal birth weight and maternal body mass index were the 2 most significant factors in predicting neonatal hypoglycemia, contributing 18.6% and 15.9%, respectively. The RNN model similarly forecasted glucose levels effectively, addressing the dynamic changes in blood glucose with 0.63 mmol/L RMSE and 0.53 mmol/L mean absolute error. CONCLUSIONS ANN and RNN models effectively predict neonatal hypoglycemia in infants of mothers with GDM, highlighting the critical role of maternal and neonatal factors.

Supporting risk management through cyberspace: An adaptive network model simulating AI coach effects by inducing adherence to guidelines in neonatal medical protocols

In this article, it is shown how second-order adaptive agent-based network models can be used to support a medical team in healthcare institutions to adhere to specific Neonatal Hypoglycemia and Neonatal Hyperbilirubinemia treatment guidelines through the integration of an Artificial Intelligence (AI) Virtual Coach. The proposed AI Coach is designed to provide timely interventions and correct deviations when lapses in the health care practitioner’s internal mental model occur. Through simulating three different scenarios, the internal dynamics of these mental models, adaptive changes of these mental models (learning and forgetting), and the interaction between health care practitioners and the world is shown when: (1) There is perfect adherence to guidelines, (2) There is imperfect adherence to guidelines and (3) There is both perfect and imperfect adherence to guidelines alongside interventions of the AI Coach in the latter case.

12503 An Observational Study Of The Glycemic Variability In Type 1 Diabetes Mellitus Women Preconception And During Pregnancy And Its Associations With Adverse Maternal And Neonatal Outcomes

Abstract Disclosure: S. Avula: None. A.R. Ankireddypalli: None. K. Tessier: None. E.R. Seaquist: None. Background: Pregnancy in T1 diabetes mellitus (T1DM) women is associated with increased risk of maternal/fetal complications. Despite glycemic optimization during pregnancy in T1DM, offspring are at increased risk for neonatal complications. Aim: To examine glycemic variability by continuous glucose monitor (CGM) preconception and during pregnancy by trimester and assess the association with adverse maternal/fetal outcomes. Methods: This was a retrospective cohort study of pregnant patients with T1DM who used real-time CGM and delivered at a U.S. tertiary center (2012-2023). Multiple gestations, Cystic fibrosis-related diabetes (CFRD), twin or multiple births, and no valid CGM data for at least one trimester were excluded. 63 met the inclusion criteria. The primary outcome was composite neonatal morbidity (CNM), including large or small for gestational age (LGA/SGA), NICU admission, neonatal hypoglycemia, shoulder dystocia, respiratory distress syndrome, APGAR 1 or 5 minutes &amp;lt; 7, prematurity (&amp;lt;37 weeks), intrauterine growth restriction (IUGR), CPAP, and ventilator. We also collected data about maternal outcomes. Results:54 patients (86%) met at least one outcome included in the CNM. 20 patients (32%) were LGA, 3 (5%) were SGA, 32 (51%) premature, 29 (46%) required NICU admission, 44 (70%) had neonatal hypoglycemia, 3 (5%) had shoulder dystocia, 23 (37%) had respiratory distress, 22 (35%) needed CPAP, 3 (5%) were on ventilator, 11 (18%) had APGAR 1 minute &amp;lt;7. Among maternal outcomes, 18 (29%) developed pre-eclampsia, and 46 (73%) had a cesarean delivery. Overall, individuals with neonatal morbidity had a lower target in range (TIR) and higher target above range(TAR), average glucose, standard deviation(SD), and coefficient of variation (CV) compared with those without the primary composite, but statistical significance was seen for average glucose and TAR. For every 5 mg/dl increase in average glucose (mean of the 3-trimester values), there was a 25% increase in odds of neonatal morbidity (OR 1.25; 95% CI 1.04-1.56; p=0.028). There was a significant association between 1st trimester SD and neonatal morbidity (OR 1.11; 95% CI 1.02-1.24; p=0.027). There was a trend toward significance between the 3rd-trimester average blood glucose and neonatal morbidity (OR 1.26; 95% CI 1.02-1.63; p=0.051). Conclusion: In our single-center cohort, we found maternal average glucose and TAR, as well as first trimester SD, were significantly associated with CNM. This confirms that maternal hyperglycemia and demonstrates that first trimester SD are associated with poorer neonatal outcomes. Presentation: 6/1/2024

7833 Gestational Diabetes Mellitus (GDM): A Weighted Spectrum of Clinical Outcomes

Abstract Disclosure: M. Moazzami: None. N. Venkatesan: None. K.S. Rajagopalan: None. A.V. Vella: None. A. Egan: None. Gestational diabetes mellitus (GDM) affects approximately 10% of pregnancies, with rates almost doubling in minority subgroups. Higher body mass index (BMI) is a significant GDM risk factor, and BMI ≥ 25kg/m2 is often used as a criterion in risk factor-based screening programs. However, up to 60% of individuals with GDM have a normal BMI, and it is unclear if this offers protection against associated adverse outcomes. Furthermore, many prior studies fail to address the fact that those of Asian descent require a lower BMI cut-off, given their different distribution of body fat. Our study evaluated GDM pregnancy outcomes using BMI as a risk indicator. We compared individuals with BMIs &amp;lt; 25 kg/m2, 25-30 kg/m2, and &amp;gt; 30 kg/m2. For individuals that self-identified as Asian, we adjusted BMI categories: &amp;lt;23 kg/m2 for normal weight, 23-30 kg/m2 for overweight, and &amp;gt;30 kg/m2 for obese. We identified 2212 subjects diagnosed with GDM via universal screening and Carpenter and Coustan criteria at our institution from 2018 - 22. In total, 508 (23.0%) were normal weight, 611 (27.6%) overweight, and 1093 (49.4%) obese. The average maternal age was 31 years. Higher proportions identified as Hispanic and non-White race in overweight and obese categories. Maternal adverse outcomes were higher in obese compared to overweight or normal BMI categories (cesarian delivery: normal 26.7 v overweight 28.3 v obese 22.7%, p&amp;lt;0.001; hypertensive disorders: normal 13.2 v overweight 12.5 v obese 22.7%, p &amp;lt;0.001). Pharmacological therapy was required in 50% with obesity versus 24.8% in normal, and 28.7% in overweight categories (p&amp;lt;0.001). While there were no differences in live birth rates across categories, infants born to mothers with obesity had a higher birthweight (normal 3.30 v overweight 3.38 v obese 3.45kg, p&amp;lt;0.001) and were more likely to have neonatal hypoglycemia (normal 28.7 v overweight 25.5 v obese 43.8%, p&amp;lt;0.001) and require intensive care unit admission (normal 8.4 v overweight 5.5 v obese 12.7%, p&amp;lt;0.001). Attendance at postpartum glucose testing varied across BMI categories with lower attendance in mothers with obesity followed by normal weight BMI (normal 40.75 v overweight 45.99 v obese 36.2%, p&amp;lt;0.001). Compared to overweight individuals, those with normal weight exhibited higher rates of postpartum glucose intolerance (12.4 v 6.9%, p =0.002). However, those with obesity had the highest rates of glucose intolerance (20.7%, p&amp;lt;0.0002). Individuals with normal weight had the highest rates of breastfeeding (normal 95.9 v overweight 92.8 v obese 91.4% p=0.006). This study highlights the nuanced relationship between BMI and pregnancy outcomes in GDM. While maternal obesity was associated with the poorest outcomes, those with normal BMI were not protected compared to overweight individuals, and experience higher rates of postpartum glucose intolerance. Presentation: 6/2/2024

7316 A Unique Presentation of Diabetes Mellitus in an 8-Year-Old Male Positive For 3 Different Mutations Related to MODY

Abstract Disclosure: R. Senguttuvan: None. A. Pamfil: None. Background: Maturity-Onset Diabetes of the Young (MODY) is the most common form of inherited non-autoimmune diabetes mellitus, characterized by autosomal dominant inheritance, young age at onset and beta cell dysfunction. There are at least 14 MODY mutations and we present a pediatric case not meeting criteria for type 1[T1DM] or type 2 diabetes mellitus[T2DM], who tested positive for mutations in 3 different genes known to cause MODY. Case: An 8-year-old male, born full term, 2776 grams and 48.3 cm, without history of neonatal hypoglycemia or hyperglycemia, was referred for new onset diabetes mellitus management. While undergoing evaluation for abdominal pain and constipation, he was found to have a fasting glucose of 126 mg/dL (7 mmol/L) and hemoglobin A1C of 6.5%. He endorsed polyuria, but no polydipsia. He had no clinical signs of insulin resistance (e.g., acanthosis nigricans) and a BMI of 23.65 kg/m2, at the 97th percentile. Family history is positive for diabetes mellitus requiring insulin, in father (diagnosed at 11 years) and paternal grandmother and T2DM in paternal aunt. Laboratory evaluation was negative for all 5 antibodies (GAD, IA-2, Anti-islet cell antibody, Zinc Transporter 8 and Insulin antibodies) and revealed an insulin level of 15.9 uIU/mL (RR: &amp;lt;2.0-13.0) and C peptide: 2.3 ng/mL (RR: 1.1-4.4). Lacking diagnostic criteria for T1DM or T2DM, genetic testing was performed. Patient tested heterozygous for mutations in 3 genes known to cause MODY: GCK [(c.350 G&amp;gt;T p. (G117V)], ABCC8 [(c.2270 C&amp;gt;G p.(T757R)], and HNF1B [(c.68A&amp;gt;G p.(K23R)], all variant of uncertain significance. Over an 8-month period, patient's weight decreased from 98 lbs. (44.9 kg) to 90 lbs. (41.1 kg) after meeting with our dietician and implementing healthy dietary changes, and his beta cell function markers improved from diagnosis: Fasting insulin (4.5 uIU/mL), C peptide (1.3 ng/mL), and glucose 119 mg/dL; Hemoglobin A1C remained relatively stable at 6.1%. A kidney ultrasound was normal. No medical intervention were started yet, and patient is being monitored clinically and biochemically every 3-4 months. Discussion: Clinical monitoring over time, genetic testing in the parents, are critical in this patient’s long-term treatment plan and prognosis. To our knowledge, this may be the first case of diabetes mellitus in a pediatric patient, positive for mutations in 3 different genes known to cause MODY. South Texas has one of the highest incidences of T2DM in the USA. In addition to screening for genetic forms of diabetes, in patients with negative T1DM antibodies and atypical phenotype for T2DM, we should consider genetic screening in mildly obese pediatric and young adult patients without significant acanthosis nigricans, who were already diagnosed as T2DM. Presentation: 6/1/2024

8129 A Case of Pituitary Stalk Interruption Syndrome Presenting With Panhypopituitarism

Abstract Disclosure: A. Salvat: None. M. Sevilla: None. Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital abnormality characterized by the classic triad of a thinned or interrupted pituitary stalk, an ectopic or absent neurohypophysis, and a hypoplastic or absent anterior pituitary gland. Clinical manifestations vary and can include neonatal hypoglycemia, short stature, cryptorchidism, and delayed puberty. Symptoms can present at birth or later in life with variable degrees of hormone deficiency. Clinical case: A 25-year-old male with hypothyroidism (on levothyroxine since age 13) presented for evaluation of hypogonadotropic hypogonadism. At birth, he was diagnosed with bilateral cryptorchidism and had frequent hypoglycemic episodes. During his childhood and early teenage years, his growth paralleled of his peers. However, at age 18, he experienced a growth spurt with unusually long arms and legs. He never developed secondary sexual characteristics. Physical examination showed blood pressure of 109/62 mmHg, height 193 cm, weight 76 kg, Tanner stage 1 pubic hair, microphallus, and nonpalpable testicles. The initial labs were consistent with panhypopituitarism: FSH 0.14 mIU/mL (0.95–11.95 mIU/mL), luteinizing hormone &amp;lt;0.09 mIU/mL (0.57–12.07 mIU/mL), total testosterone &amp;lt;4 ng/dL (240–871 ng/dL), prolactin 30.31 ng/dL (3.46–19.40 ng/dL), AM cortisol &amp;lt;1 ug/dL (3.7–19.4 ug/dL), ACTH 14 pg/mL (6–50 pg/mL ), cortisol levels 60 minutes after consyntropin stimulation test of 3.6 ug/dL (3.7–19.4 ug/dL), IFG-1 &amp;lt;16 ng/mL (63–373 ng/mL), TSH 7.24 uIU/mL (0.35–4.94 uIU/mL), free T4 0.53 ng/dL (0.70–1.48 ng/dL). Karyotype 46, XY, inv (9) (p12q13). The whole exome sequencing testing was negative. Pituitary magnetic resonance imaging showed hypoplasia of the anterior pituitary gland, ectopic location of the posterior pituitary gland at the expected base of the pituitary infundibulum anterior to the mammary bodies, and hypoplastic or absent pituitary infundibulum, findings suggestive of pituitary stalk interruption syndrome. Scrotal ultrasound showed no testicular or epididymal tissue within the scrotum. DEXA scan showed osteoporosis associated with a long history of non-treated testosterone deficiency. The levothyroxine was adjusted, and the patient was started on intramuscular testosterone, calcium, and vitamin D to manage the hypogonadism and improve the bone mineral density. Conclusion: Diagnosis of PSIS is often delayed due to its variable presentation and age of onset. Although this condition is considered rare, it should be in the differential diagnosis of patients presenting with panhypopituitarism. Early identification of deficient hormones, as well as prompt initialization of hormone replacement therapy, is essential to prevent serious complications associated with these deficiencies, such as adrenal crisis, osteoporosis, diminished quality of life, delayed puberty, and infertility. Presentation: 6/3/2024

Increased Maternal BMI at Time of Delivery Associated with Poor Maternal and Neonatal Outcomes.

Current literature on the risks and outcomes of obesity in pregnancy almost exclusively utilizes prepregnancy body mass index (BMI). Given the rising obesity rate across the United States along with a paucity of available information on the relationship between delivery BMI and maternal and neonatal outcomes, our study aimed to determine the association of maternal BMI at delivery with antepartum, intrapartum, and neonatal complications at an academic referral hospital. This study is a secondary analysis of data collected for a prospective cohort study of Coronavirus Disease-2019 (COVID-19) in pregnancy. This analysis included all patients who delivered term singleton infants between May 1, 2020, and April 30, 2021, at the University of Iowa Hospitals and Clinics. Demographic and clinical data were obtained from the electronic medical record. The relationship between maternal BMI and maternal and neonatal characteristics of interest was assessed using logistic regression models. A statistical significance threshold of 0.05 was used for all comparisons. There were 1,996 women who delivered term singleton infants during the study period. The median BMI at delivery was 31.7 kg/m2 (interquartile range: 27.9, 37.2), with 61.1% of women having a BMI ≥ 30.0 kg/m2. Increasing BMI was significantly associated with nonreassuring fetal status, unscheduled cesarean birth, overall cesarean birth rate, postpartum hemorrhage, prolonged postpartum stay, hypertensive diseases of pregnancy, neonatal hypoglycemia, neonatal intensive care unit admission, decreased APGAR score at 1 minute, and increasing neonatal birth weight. Even when controlling for preexisting hypertension in a multivariate model, increasing BMI was associated with gestational hypertension and preeclampsia. Increased maternal BMI at delivery was associated with adverse perinatal outcomes. These findings have implications for clinical counseling regarding risks of pregnancy and delivery for overweight and obese patients and may help inform future studies to improve safety, especially by examining reasons for high cesarean rates. · Sixty-one percent of delivering patients had a BMI330 kg/m2 at delivery.. · There was a higher cesarean rate with increasing delivery BMI.. · For every 5-unit increase in maternal BMI, neonatal weight increased by 0.47 g..

Gestational diabetes mellitus - Neonatal and maternal outcomes in women treated with insulin or diet: A propensity matched analysis

AimsPregnant women worldwide face the risk of developing gestational diabetes mellitus (GDM), if left untreated, can cause complications. The study explores factors influencing the choice between diet control and insulin therapy for pregnant women with GDM. It aims to understand how these choices impact maternal and neonatal outcomes. MethodsIn this quasi-experimental study, clinicians determined treatment (diet control or insulin) for 1030 individuals with GDM at a private practice from 2010 to 2020 based on baseline characteristics. Propensity scores (PS), reflecting the probability of treatment allocation, were derived through multiple logistic regression. ResultsAfter PS matching, 386 individuals were paired from two study groups. The insulin-treated group exhibited a 4.43 times higher risk of neonatal hypoglycemia than the diet group. Insulin-treated individuals, stratified by PS, revealed that the high-risk quartile had significantly higher mean insulin requirements and a doubled dose at full term compared to the lower-risk quartiles. The mean insulin dose did not significantly differ in the first three quartiles, but the last quartile showed a significant increase (p = 0.008), particularly for individuals with PS exceeding 0.70, indicating a higher insulin dose requirement for effective glucose control. ConclusionThis study reveals that individuals with a bad obstetrics history, a family history of diabetes, obesity, and elevated baseline glycemic parameters necessitate higher insulin doses. This insight improves clinicians' decision-making in diagnosis and treatment planning, enhancing the precision of medical practices.