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Hypoglycemia is a common metabolic disorder that occurs in the neonatal period. Early identification of neonates at risk of developing hypoglycemia can optimize therapeutic strategies in neonatal care. This study aims to develop a machine learning model and implement a predictive application to assist clinicians in accurately predicting the risk of neonatal hypoglycemia within four hours after birth. Our retrospective study analyzed data from neonates born ≥35 weeks gestational age and admitted to the well-baby nursery between 1 January 2011 and 31 August 2021. We collected electronic medical records of 2687 neonates from a tertiary medical center in Southern Taiwan. Using 12 clinically relevant features, we evaluated nine machine learning approaches to build the predictive models. We selected the models with the highest area under the receiver operating characteristic curve (AUC) for integration into our hospital information system (HIS). The top three AUC values for the early neonatal hypoglycemia prediction models were 0.739 for Stacking, 0.732 for Random Forest and 0.732 for Voting. Random Forest is considered the best model because it has a relatively high AUC and shows no significant overfitting (accuracy of 0.658, sensitivity of 0.682, specificity of 0.649, F1 score of 0.517 and precision of 0.417). The best model was incorporated in the web-based application integrated into the hospital information system. Shapley Additive Explanation (SHAP) values indicated mode of delivery, gestational age, multiparity, respiratory distress, and birth weight < 2500 gm as the top five predictors of neonatal hypoglycemia. The implementation of our machine learning model provides an effective tool that assists clinicians in accurately identifying at-risk neonates for early neonatal hypoglycemia, thereby allowing timely interventions and treatments. [ABSTRACT FROM AUTHOR]

Hirata disease, also known as insulin autoimmune syndrome (IAS), is a rare cause of hypoglycemia, due to the presence of insulin autoantibodies (IAA) in the circulating blood. These antibodies are immunoglobulin G (IgG), making placental transfer to the fetus possible. To our knowledge, no reports of IAS have been previously described in the neonatal population. We present a case report of hypoglycemia due to a secondary IAS in a neonate and discuss the management and treatment of the disease. [ABSTRACT FROM AUTHOR]

Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007). Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants. What is Known: • Parenteral nutrition may affect glucose profile during the first days of life of preterm infants. What is New: • Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges. [ABSTRACT FROM AUTHOR]

Neonatal hypoglycemia is a common disease in newborns, which can precipitate energy shortage and follow by irreversible brain and neurological injury. Herein, we present a novel approach for treating neonatal hypoglycemia involving an adhesive polyvinylpyrrolidone/gallic acid (PVP/GA) film loading glucose. The PVP/GA film with loose cross-linking can be obtained by mixing their ethanol solution and drying complex. When depositing this soft film onto wet tissue, it can absorb interfacial water to form a hydrogel with a rough surface, which facilitates tight contact between the hydrogel and tissue. Meanwhile, the functional groups in the hydrogels and tissues establish both covalent and non-covalent bonds, leading to robust bioadhesion. Moreover, the adhered PVP/GA hydrogel can be detached without damaging tissue as needed. Furthermore, the PVP/GA films exhibit excellent antibacterial properties and biocompatibility. Notably, these films effectively load glucose and deliver it to the sublingual tissue of newborn rabbits, showcasing a compelling therapeutic effect against neonatal hypoglycemia. The strengths of the PVP/GA film encompass excellent wet adhesion in the wet and highly dynamic environment of the oral cavity, on-demand detachment, antibacterial efficacy, biocompatibility, and straightforward preparation. Consequently, this innovative film holds promise for diverse biomedical applications, including but not limited to wearable devices, sealants, and drug delivery systems. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundUnlike in developed countries, neonatal morbidity and mortality are the leading challenges associated with easily preventable and treatable disorders during the neonatal period in low- and middle-income countries. However, evidence-based data about prolonged transitional hypoglycemia and associated factors are highly limited in Ethiopia and resource-limited countries.MethodsAn institution-based prospective cross-sectional study was conducted at public hospitals in South Gondar in neonatal intensive care units (NICUs). The data were entered and analyzed using SPSS version 23. Descriptive statistics were used to summarize maternal characteristics. Multivariate binary logistic regression at a p value

Introduction: Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia. Methods: A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing. Results: All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was 2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 – 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months. Conclusion: The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted.

Introduction: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5‐min Apgar score, and preterm birth. Material and methods: This Swedish population‐based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019–2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual‐level, linkage register‐data in multivariable logistic regression models. Results: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74–0.96), vs MIT (0.74 [0.64–0.87]), and vs IT (0.47 [0.40–0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99–1.30]) and with lower risk vs IT (0.63 [0.53–0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5‐min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories. Conclusions: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors. [ABSTRACT FROM AUTHOR]

Neonatal hypoglycemia presents significant challenges in the management of small for gestational age (SGA) infants with early onset sepsis. This literature review and case report examine the clinical implications and therapeutic strategies in such cases. The study underscores the importance of timely recognition and intervention to mitigate the risks associated with hypoglycemia and sepsis in term newborns, emphasizing early glucose management and appropriate antibiotic therapy for optimal outcomes [ABSTRACT FROM AUTHOR]

Introduction: Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia. Methods: A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing. Results: All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was <50 mg/dl), hyperinsulinism (Insulin >2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 - 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months. Conclusion: The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted. [ABSTRACT FROM AUTHOR]

We aimed to identify perinatal risk factors associated with hyperinsulinemic hypoglycemia in neonates. Secondary objectives included an examination of clinical and biochemical characteristics at the time of diagnosis and an exploration of the duration of diazoxide therapy. A case-control study was conducted, involving individual chart reviews of inborn infants diagnosed with hyperinsulinemic hypoglycemia (the HH group) between 2014 and 2021. These cases were paired with controls (the non-HH group) belonging to the same gestational age (GA) strata who did not exhibit HH or only had transient postnatal hypoglycemia. A total of 52 infants with HH were matched with corresponding controls. The mean GA in the HH group was 34.4 ± 3.1 weeks. Notably, the HH group exhibited lower mean minimum plasma glucose (PG) levels and required higher glucose infusion rates in comparison to the non-HH group (26.5 ± 15.6 vs. 49.1 ± 37.7 mg/dL and 12.9 ± 3.8 vs. 5.7 ± 2.1 mg/kg/min, respectively; p<0.001 for both). After adjusting for potential confounding factors, only two variables, fetal growth restriction (FGR) and neonatal sepsis, demonstrated significant associations with HH (adjusted odds ratio [95 % confidence interval]: 8.1 [2.1–31.0], p=0.002 and 6.3 [1.9–21.4], p=0.003, respectively). The median duration of diazoxide therapy for the HH group was 4 months. FGR and neonatal sepsis emerged as notable risk factors for HH. These infants exhibited lower PG levels and necessitated higher glucose infusion rates compared to their non-HH counterparts. Importantly, a substantial proportion of the HH group received diazoxide therapy, with a median treatment duration of 4 months. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between continuous glucose monitoring (CGM) during pregnancy and antepartum glucose with the risk of neonatal hypoglycemia in women with type 1 diabetes mellitus (T1DM). Methods This study was a multicenter, prospective, observational cohort study. Pregnant women with T1DM from 11 hospitals nationwide were enrolled from January 2015 to December 2017. CGM was used for glycemic control in pregnancy. Antepartum 2-hour capillary blood glucose and neonatal outcomes were recorded. A total of 73 women who used CGM during pregnancy were included in the study and divided into the neonatal hypoglycemia group (14 cases) and the neonatal normoglycemia group (59 cases) based on neonatal capillary glucose (neonatal hypoglycemia defined as<2.2 mmol/L) after delivery. Data on maternal glycated hemoglobin A1c (HbA1c), CGM metrics [mean blood glucose, time in range (TIR), time above range (TAR1>7.8 mmol/L, TAR2>13.9 mmol/L), time below range (TBR), standard deviation of blood glucose (SDBG), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV)] during pregnancy, antepartum 2-hour blood glucose levels, gestational age at delivery, and neonatal obstetric outcomes [birth weight, birth length, premature delivery, neonatal intensive care unit (NICU) admission] were compared between groups. Comparisons between groups were made using the two independent samples t test, rank sum test, χ² test and Fisher exact test. The influencing factors of neonatal hypoglycemia were analyzed by multivariate logistic regression models. Results Compared with neonatal normoglycemia group, women in the neonatal hypoglycemia group had higher mean blood glucose [(6.91±0.71) vs. (6.38±0.81) mmol/L, t=2.041, P<0.05], TAR2 [0.81% (0, 4.36%) vs. 0 (0, 0.64%), Z=2.064, P<0.05], and MAGE [(6.42±3.24) vs. (4.60±1.67) mmol/L, t=2.137, P<0.05] in the first trimester (P<0.05). Antepartum 2-hour blood glucose was higher in the neonatal hypoglycemia group [(7.75±2.22) vs. (6.13±2.10) mmol/L, t=2.324, P<0.05]. The incidences of preterm birth [35.71% (5/14) vs. 11.86% (7/59), χ2=4.686, P< 0.05] and NICU admission [71.43% (10/14) vs. 32.20% (19/59), χ2=5.725, P<0.05] were higher in the neonatal hypoglycemia group than in the neonatal normoglycemia group (P<0.05). The multivariate logistic regression analysis revealed that antepartum 2-hour blood glucose was the independent influencing factor of neonatal hypoglycemia (OR=2.23, 95%CI 1.09-4.54, P<0.05). Conclusions Increased mean blood glucose, TAR, and MAGE in the first trimester were associated with a higher risk of neonatal hypoglycemia in pregnant women with T1DM. Antepartum 2-hour blood glucose was independently associated with the risk of neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

Hypoglycemia is a common metabolic disorder that occurs in the neonatal period. Early identification of neonates at risk of developing hypoglycemia can optimize therapeutic strategies in neonatal care. This study aims to develop a machine learning model and implement a predictive application to assist clinicians in accurately predicting the risk of neonatal hypoglycemia within four hours after birth. Our retrospective study analyzed data from neonates born ≥35 weeks gestational age and admitted to the well-baby nursery between 1 January 2011 and 31 August 2021. We collected electronic medical records of 2687 neonates from a tertiary medical center in Southern Taiwan. Using 12 clinically relevant features, we evaluated nine machine learning approaches to build the predictive models. We selected the models with the highest area under the receiver operating characteristic curve (AUC) for integration into our hospital information system (HIS). The top three AUC values for the early neonatal hypoglycemia prediction models were 0.739 for Stacking, 0.732 for Random Forest and 0.732 for Voting. Random Forest is considered the best model because it has a relatively high AUC and shows no significant overfitting (accuracy of 0.658, sensitivity of 0.682, specificity of 0.649, F1 score of 0.517 and precision of 0.417). The best model was incorporated in the web-based application integrated into the hospital information system. Shapley Additive Explanation (SHAP) values indicated mode of delivery, gestational age, multiparity, respiratory distress, and birth weight < 2500 gm as the top five predictors of neonatal hypoglycemia. The implementation of our machine learning model provides an effective tool that assists clinicians in accurately identifying at-risk neonates for early neonatal hypoglycemia, thereby allowing timely interventions and treatments.

Background: It's challenging for healthcare workers to detect neonatal hypoglycemia due to its rapid progression and lack of aura symptoms. This may lead to brain function impairment for the newborn, placing a significant care burden on the family and creating an economic burden for society. Tools for early diagnosis of neonatal hypoglycemia are lacking. This study aimed to identify newborns at high risk of developing neonatal hypoglycemia earlybydeveloping a riskpredictionmodel. Methods: Using a retrospective design, pairs (470) of women and their newborns in a tertiary hospital from December 2021 to September 2022 were included in this study. Socio-demographic data and clinical data of mothers and newborns were collected. Univariate and multivariate logistic regression were used to screen optimized factors. A neonatal hypoglycemia risk nomogram was constructed using R software, and the calibration curve and receiver operator characteristic curve (ROC) was utilized to evaluate model performance. Results: Factors integrated into the prediction risk nomogram were maternal age (odds ratio [OR] =1.10, 95% CI: 1.04, 1.17), fasting period (OR=1.07, 95% CI: 1.03, 1.12), ritodrine use (OR=2.00, 95% CI: 1.05, 3.88), gestational diabetes mellitus (OR=2.13, 95% CI: 1.30, 3.50), gestational week (OR=0.80, 95% CI: 0.66, 0.96), fetal distress (OR=1.76, 95% CI: 1.11, 2.79) and neonatal body mass index (OR=1.50, 95% CI: 1.24, 1.84). The area under the curve (AUC) was 0.79 (95% confidence interval [CI]: 0.75, 0.82), specificity was 0.82, and sensitivity was 0.62. Conclusion: The prediction model of this study demonstrated good predictive performance. The development of the model identifies advancing maternal age, an extended fasting period before delivery, ritodrine use, gestational diabetes mellitus diagnosis, fetal distress diagnosis and an increase in neonatal body mass index increase the probability of developing neonatal hypoglycemia, while an extended gestational week reduces the probability of developing neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypoglycemia in neonates is common and contributes to 4.0–5.8% of neonatal intensive care unit (NICU) admissions. In utero nicotine exposure is underexplored as a potential contributor to neonatal hypoglycemia. Rat models have shown that in utero nicotine exposure can be associated with a reduction in pancreatic beta cell mass, leading to glucose dysregulation. The primary aim of this work is to study the risk of developing hypoglycemia after birth in a population of in utero nicotine-exposed neonates. METHODS: We conducted a retrospective matched cohort study that augmented an existing dataset of neonates admitted to a level IV NICU with household-based in utero nicotine exposure (N = 335). Neonates in the control group parents denied household smoking (N = 325), were born within a 6-month timeframe, and were within a birthweight of 50 grams of a nicotine-exposed neonate. Data reviewed included gestational age, growth parameters, maternal history of diabetes, and glucose levels within the first three hours of life per unit protocol. RESULTS: 660 neonates were included in the analysis. In utero nicotine exposure demonstrated a 94.3% posterior probability (PP) for greater hypoglycemia risk (RR = 1.185, 95% CrI = [0.953, 1.445]). A 94.6% PP was demonstrated when neonates who were small for gestational age, intrauterine growth-restricted, and born to diabetic mothers were excluded (n = 482; RR = 1.271, 95% CrI = [0.946, 1.669]). CONCLUSION: Nicotine exposure in utero was found to be a potential risk factor for developing hypoglycemia after birth. Mechanisms of action should be explored, and additional research on in utero nicotine exposure risks should follow. [ABSTRACT FROM AUTHOR]

Hypoglycemia represents one of the most frequent metabolic disturbances of the neonate, associated with increased morbidity and mortality, especially if left untreated or diagnosed after the establishment of brain damage. The aim of this study was to review and compare the recommendations from the most recently published influential guidelines on the diagnosis, screening, prevention and management of this common neonatal complication. Therefore, a descriptive review of the guidelines from the American Academy of Pediatrics (AAP), the British Association of Perinatal Medicine (BAPM), the European Foundation for the Care of the Newborn Infants (EFCNI), the Queensland Clinical Guidelines-Australia (AUS), the Canadian Pediatric Society (CPS) and the Pediatric Endocrine Society (PES) on neonatal hypoglycemia was carried out. There is a consensus among the reviewed guidelines on the risk factors, the clinical signs and symptoms of NH, and the main preventive strategies. Additionally, the importance of early recognition of at-risk infants, timely identification of NH and prompt initiation of treatment in optimizing the outcomes of hypoglycemic neonates are universally highlighted. All medical societies, except PES, recommend screening for NH in asymptomatic high-risk and symptomatic newborn infants, but they do not provide consistent screening approaches. Moreover, the reviewed guidelines point out that the diagnosis of NH should be confirmed by laboratory methods of BGL measurement, although treatment should not be delayed until the results become available. The definition of NH lacks uniformity and it is generally agreed that a single BG value cannot accurately define this clinical entity. Therefore, all medical societies support the use of operational thresholds for the management of NH, although discrepancies exist regarding the recommended cut-off values, the optimal treatment and surveillance strategies of both symptomatic and asymptomatic hypoglycemic neonates as well as the treatment targets. Over the past several decades, ΝH has remained an issue of keen debate as it is a preventable cause of brain injury and neurodevelopmental impairment; however, there is no clear definition or consistent treatment policies. Thus, the establishment of specific diagnostic criteria and uniform protocols for the management of this common biochemical disorder is of paramount importance as it will hopefully allow for the early identification of infants at risk, the establishment of efficient preventive measures, the optimal treatment in the first hours of a neonate's life and, subsequently, the improvement of neonatal outcomes. [ABSTRACT FROM AUTHOR]

Neonatal hypoglycemia affects up to 15% of all newborns. Despite the high prevalence there is no uniform definition of neonatal hypoglycemia, and existing guidelines differ significantly in terms of when and whom to screen for hypoglycemia, and where to set interventional thresholds and treatment goals. In this review, we discuss the difficulties to define hypoglycemia in neonates. Existing knowledge on different strategies to approach this problem will be reviewed with a focus on long-term neurodevelopmental outcome studies and results of interventional trials. Furthermore, we compare existing guidelines on the screening and management of neonatal hypoglycemia. We summarize that evidence-based knowledge about whom to screen, how to screen, and how to manage neonatal hypoglycemia is limited - particularly regarding operational thresholds (single values at which to intervene) and treatment goals (what blood glucose to aim for) to reliably prevent neurodevelopmental sequelae. These research gaps need to be addressed in future studies, systematically comparing different management strategies to progressively optimize the balance between prevention of neurodevelopmental sequelae and the burden of diagnostic or therapeutic procedures. Unfortunately, such studies are exceptionally challenging because they require large numbers of participants to be followed for years, as mild but relevant neurological consequences may not become apparent until midchildhood or even later. Until there is clear, reproducible evidence on what blood glucose levels may be tolerated without negative impact, the operational threshold needs to include some safety margin to prevent potential long-term neurocognitive impairment from outweighing the short-term burden of hypoglycemia prevention during neonatal period. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Kabuki syndrome is a congenital condition characterized by a set of facial dysmorphic features that often help the clinician to suspect the diagnosis. However, more insidious symptoms can rarely occur, such as manifestations of hypoglycemia in newborns with congenital hyperinsulinism hypoglycemia, especially when a variant of the KDM6A gene is found. In those cases, a treatment with diazoxide can be started and can be replaced with lanreotide if a satisfying glycemic control is not achieved. We report the case of a female patient born at 37 weeks of gestational age, without any obvious facial dysmorphic features, after a non‐complicated pregnancy, that presented with feeding difficulties, drowsiness, and irritability revealing a hyperinsulinemic hypoglycemia. Further testing at 6 months old found a KDM6A mutation. The patient was initially treated by diazoxide alone, but its dosage had to be lowered because of the occurrence of treatment side effects, and lanreotide had been added to maintain acceptable blood sugar levels. A congenital hyperinsulinemia hypoglycemia revealed heterozygous truncating variant in the KDM6A gene, also known as X‐linked Kabuki syndrome in a newborn. In cases of neonatal hypoglycemia, the first‐line therapy is diazoxide. Our report shows that analogues of somatostatin such as lanreotide should be considered if the diazoxide regimen is not tolerated. [ABSTRACT FROM AUTHOR]

Abstract Background Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2). Case presentation We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis. Conclusions CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.

Aim: We investigated associations of maternal obesity with late gestational diabetes mellitus (GDM) diagnosis (>34 weeks) in women with previous normal glucose screening, and associations of late GDM with obstetrical outcomes. Methods: This retrospective cohort study assessed obstetrical and neonatal outcomes of 238 women with normal (24–28 week) glucose screening results, who underwent late repeat oral glucose tolerance tests (OGTT) (>34 weeks) due to a suspected LGA fetus (54.6%) or polyhydramnios (45.4%). A sub‐analysis was performed of outcomes of women with late versus mid‐trimester GDM. Results: The GDM rate in repeat OGTT screening was 22.2% for the total sample, and 33% among women with morbid obesity. Among women with late GDM versus without late GDM, rates were higher for macrosomia, large‐for‐gestational‐age fetus induction of labor, neonatal hypoglycemia, jaundice, and the need for phototherapy. Among women with late GDM, a higher pregestational BMI was associated with adverse maternal and perinatal outcomes. Higher risks for macrosomia and CS due to macrosomia were demonstrated in women with late vs. mid‐trimester GDM. Conclusion: Late screening in pregnancy may reveal GDM among women with previous normal glucose screening, particularly among those with late third trimester BMI ≥ 35 kg/m2, GDM in a previous pregnancy or fasting glucose >95 mg/dl. Women diagnosed with GDM at >34 weeks following normal glucose screening at 24–28 weeks are at higher risk for adverse perinatal outcomes. For women with morbid obesity, or suspected macrosomia or polyhydramnios in the late third trimester, and normal glucose screening in the second trimester, retesting should be considered. [ABSTRACT FROM AUTHOR]

Neonates at risk of hypoglycemia are often roomed in with mothers, but there is paucity of literature on the occurrence of hypoglycemia in these exclusively breastfed high-risk neonates. The primary objective was to estimate the incidence of hypoglycaemia in high-risk neonates on exclusive breastfeeding. The secondary objectives were to study the time of presentation, symptoms of hypoglycaemia, and the various maternal and neonatal risk factors. This prospective observational study was carried out in a tertiary care teaching hospital of eastern India between January 2017 and June 2018. All neonates roomed in with mothers with high-risk factors such as low birth weight, preterm, small for gestational age, large for gestational age and infants of diabetic mothers were included. All included neonates were exclusive breastfed and underwent blood glucose monitoring at 2, 6, 12, 24, 48 and 72 h of life using glucometer strips and also whenever clinical features suggested hypoglycaemia. Hypoglycemia was defined as the blood glucose level ≤46 mg/dL. Of a total of 250 neonates studied, 52 (20.8%) developed hypoglycaemia in first 72 h. Hypoglycaemia was detected in most at 2 h with the second peak at 48 h of age. Only 8 (3.2%) neonates had symptomatic hypoglycaemia with jitteriness being the commonest symptom, followed by lethargy and poor feeding. There is a need to closely monitor the blood glucose levels for at least first 48 h in high-risk neonates roomed in with mothers on exclusive breastfeeding. [ABSTRACT FROM AUTHOR]

Key Clinical Message Kabuki syndrome is a congenital condition characterized by a set of facial dysmorphic features that often help the clinician to suspect the diagnosis. However, more insidious symptoms can rarely occur, such as manifestations of hypoglycemia in newborns with congenital hyperinsulinism hypoglycemia, especially when a variant of the KDM6A gene is found. In those cases, a treatment with diazoxide can be started and can be replaced with lanreotide if a satisfying glycemic control is not achieved. We report the case of a female patient born at 37 weeks of gestational age, without any obvious facial dysmorphic features, after a non‐complicated pregnancy, that presented with feeding difficulties, drowsiness, and irritability revealing a hyperinsulinemic hypoglycemia. Further testing at 6 months old found a KDM6A mutation. The patient was initially treated by diazoxide alone, but its dosage had to be lowered because of the occurrence of treatment side effects, and lanreotide had been added to maintain acceptable blood sugar levels. A congenital hyperinsulinemia hypoglycemia revealed heterozygous truncating variant in the KDM6A gene, also known as X‐linked Kabuki syndrome in a newborn. In cases of neonatal hypoglycemia, the first‐line therapy is diazoxide. Our report shows that analogues of somatostatin such as lanreotide should be considered if the diazoxide regimen is not tolerated.

Neonatal hypoglycemia affects up to 15% of all newborns. Despite the high prevalence there is no uniform definition of neonatal hypoglycemia, and existing guidelines differ significantly in terms of when and whom to screen for hypoglycemia, and where to set interventional thresholds and treatment goals. In this review, we discuss the difficulties to define hypoglycemia in neonates. Existing knowledge on different strategies to approach this problem will be reviewed with a focus on long-term neurodevelopmental outcome studies and results of interventional trials. Furthermore, we compare existing guidelines on the screening and management of neonatal hypoglycemia. We summarize that evidence-based knowledge about whom to screen, how to screen, and how to manage neonatal hypoglycemia is limited – particularly regarding operational thresholds (single values at which to intervene) and treatment goals (what blood glucose to aim for) to reliably prevent neurodevelopmental sequelae. These research gaps need to be addressed in future studies, systematically comparing different management strategies to progressively optimize the balance between prevention of neurodevelopmental sequelae and the burden of diagnostic or therapeutic procedures. Unfortunately, such studies are exceptionally challenging because they require large numbers of participants to be followed for years, as mild but relevant neurological consequences may not become apparent until mid-childhood or even later. Until there is clear, reproducible evidence on what blood glucose levels may be tolerated without negative impact, the operational threshold needs to include some safety margin to prevent potential long-term neurocognitive impairment from outweighing the short-term burden of hypoglycemia prevention during neonatal period.

Abstract Background CHARGE syndrome (CS) is an autosomal dominant genetic condition whose recognition in the neonatal period is complicated by considerable phenotypic variability. Pediatric patients with genetic disorders have a known high incidence of hypoglycemia, due to many concurring factors. To date, neonatal hypoglycemia is a feature poorly explored in the literature associated with CS. This paper adds to the existing literature on hypoglycemia in CS and provides a brief review of the mechanisms through which CS, as well as the main genetic syndromes associated with neonatal hypoglycemia, may determine it. Case presentation The patient was a term newborn, first-born daughter to non-consanguineous parents. At birth, axial hypotonia with slight hypertonia of the limbs, and dysplastic auricles were noted. The incidental finding of asymptomatic hypoglycemia led to the initiation of glucose infusion on the II day of life, continued for a total of 8 days (maximum infusion rate: 8 mg/kg/min). In-depth endocrinological examinations showed poor cortisol response to the hypoglycemic stimulus, with normal GH values, thyroid function and ACTH. In view of the suspected hypoadrenalism, oral hydrocortisone therapy was initiated. Inappropriately low values of plasmatic and urinary ketones supported the hypothesis of concomitant transient hyperinsulinism, not requiring therapy. A brain MRI was performed, documenting thinning of the optic nerves, non-displayable olfactory bulbs and dysmorphic corpus callosum. An eye examination revealed bilateral chorioretinal coloboma. Temporal bone CT scan showed absence of the semicircular canals. The unexpected findings of coloboma and absence of semicircular canals led to the suspicion of CS, later confirmed by the molecular analysis of CHD7. Conclusions It seems important to consider CS in the differential diagnosis of persistent hypoglycemia in newborns with specific anomalies. At the same time, it is advisable to consider the risk of hypoglycemia in children with CS, as well as other genetic syndromes. Awareness of the many possible causes of hypoglycemia in newborns with genetic conditions may help steer the investigations, allowing for an appropriate and timely treatment.

The article focuses on the challenges associated with point-of-care glucose measurements in managing hypoglycemia in neonates. It highlights issues related to the accuracy and precision of POCT (Point-of-Care Testing) glucose meters compared to central laboratory methods, noting discrepancies that can affect clinical decisions. It emphasizes the need for regular performance evaluations and potential adjustments in treatment thresholds to account for measurement biases.

OBJECTIVE: The necessity of administering antenatal corticosteroids in early-term neonates delivered by planned cesarean delivery remains arbitrary as their observed benefit addresses a few cases that may need pulmonary resuscitation. However, to date, whether the use of antenatal corticosteroids in the preterm period is associated with neonatal hypoglycemia, which is the most prominent neonatal side effect during this period, remains unknown. This study aimed to determine the effect of antenatal corticosteroids administered during the early term period on neonatal hypoglycemia rates. DATA SOURCES: The databases of Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar were used. STUDY ELIGIBILITY CRITERIA: Published clinical trials and observational studies were considered eligible. METHODS: A modified data form that was based on the Cochrane data collection form for intervention reviews for randomized controlled trials and nonrandomized controlled trials was used. Meta-analysis was performed using RStudio (RStudio, Inc, Boston, MA). The quality of included studies was assessed with the Risk Of Bias In Non-randomized Studies of Interventions tool. Trial sequential analysis was performed to evaluate the sample size. RESULTS: A total of 6 studies of moderate risk of bias were included in this systematic review consisting of 1273 parturients, of whom 537 received corticosteroids. The risk of neonatal hypoglycemia did not increase with the use of antenatal corticosteroids before early-term elective cesarean delivery (odds ratio, 1.80; 95% confidence interval, 0.45–7.25). Similarly, the risk of admission to the neonatal intensive care unit for respiratory distress syndrome or transient tachypnoea of the newborn was not affected by the use of corticosteroids (odds ratio, 0.61; 95% confidence interval, 0.19–1.99). CONCLUSION: The use of antenatal corticosteroids did not seem to increase the risk of neonatal hypoglycemia. Given the quality and sample size of included studies, the effect size cannot be accounted for as definitive and cannot be directly applied in clinical practice. However, the provided information can be used as a guide for women participating in future trials.

To explore the association between abnormal uterine artery Dopplers (combined PI > 2.5) - with normal PAPP-A - and adverse obstetric/neonatal outcomes. This was a retrospective cohort study of 800 patients between 1 March 2019 − 23 November 2021 in a tertiary UK hospital, where it is routine to measure uterine artery Dopplers of all pregnancies during their anomaly scans. 400 nulliparous women/birthing people with complete data were included. 400 nulliparous controls scanned in the same time frame (1.5 years) with normal PAPP-A and uterine artery Dopplers were matched for age and BMI. Outcomes included: mode of birth, postpartum complications, birth weight/centile, Apgar score, gestational age at delivery, neonatal unit admission, and clinical neonatal hypoglycemia. Multivariable analysis was used. Compared to controls, pregnancies with abnormal uterine artery Dopplers and normal PAPP-A were at increased risk of induction (46.5% vs 35.5%, p =.042), cesarean section (46.0% vs 38.0%, p =.002), emergency cesarean section (35.0% vs 26.5%, p =.009), and pre-eclampsia 5.8% vs 2.5%, p =.021). Their babies were more likely to be admitted to the neonatal unit – mostly for prematurity (15.3% vs 6.3%, p =.0004), hypoglycemia (4.0% vs 1.0%, p =.007), be small for gestational age (26.5% vs 11.5%, p =.0001), had intrauterine growth restriction (10.8% vs 1.3%, p =.0001), and be born prematurely (10.0% vs 3.5%, p =.002). Routine measurement of uterine artery Dopplers increased the detection rate of small for gestational age fetuses by 15.1%. Over half of the babies admitted with neonatal hypoglycemia in pregnancies with abnormal uterine artery Dopplers had an unexplained cause. Pregnancies with abnormal uterine Dopplers are not only at increased risk of pre-eclampsia and small for gestational age fetuses/intrauterine growth restriction, but are also at increased risk of emergency cesarean section and adverse neonatal outcomes. The increased incidence of neonatal hypoglycemia is likely driven to some degree by prematurity and placental complications, but possibly also by undiagnosed glucose dysmetabolism. This may warrant routine measurement of uterine artery Dopplers in all pregnancies (regardless of risk), where feasible, to aid antenatal management and counseling. What are the novel findings of this work? Pregnancies with abnormal uterine artery Dopplers at the time of the anomaly scan and normal PAPP-A are at increased risk of having pre-eclampsia, small for gestational age fetuses, emergency cesarean, neonatal unit admission (including but not limited to prematurity), and neonatal hypoglycemia. What are the clinical implications of this work? Due to the significantly increased risk of adverse maternal and neonatal outcomes in first time mothers with increased uterine artery Dopplers despite normal PAPP-A, ultrasound assessment of placental function should be offered to all during their anomaly scans, subject to resources, to aid antenatal management and counseling. Further research is needed into undiagnosed diabetes. [ABSTRACT FROM AUTHOR]

To explore whether antenatal dexamethasone impacts postnatal serum cortisol levels in stable late preterm (LPT) infants. Secondary outcomes were to identify short-term hospital outcomes related to antenatal dexamethasone exposure. A prospective cohort study of serial serum cortisol levels in LPT infants within 3 h of birth, and at 1, 3, and 14 postnatal days. Serum cortisol levels were compared between infants exposed to antenatal dexamethasone >3 h and <14 days prior to delivery (aDex) and those who either did not receive dexamethasone or were exposed < 3 h or >14 days prior to delivery (no-aDex). Thirty-two LPT infants (aDex) were compared with 29 infants (no-aDEX). Group demographic characteristics were similar. Serum cortisol levels were identical between the groups at all 4-time points. Cumulative antenatal dexamethasone exposure ranged from 0 to 12 doses. Post-hoc analysis of the 24-hour serum cortisol levels indicated a significant difference between 1 to 3 cumulative doses versus 4 or more doses (p =.01). Only 1 infant in the aDex group had a cortisol level <3rd percentile of the reference value. Rates of hypoglycemia (absolute difference [95% CI] − 1.0 [–16.0,15.0]; p =.90) and mechanical ventilation were similar in both groups (absolute difference [95%CI] − 0.3 [–9.3,8.7]; p =.94). No deaths occurred. Antenatal dexamethasone administered 14 days prior to delivery did not affect serum cortisol levels and short-term hospital outcomes in stable LPT infants. Exposure to low cumulative doses of dexamethasone resulted in transient low serum cortisol levels compared to 4 or more doses only at 24-hours. [ABSTRACT FROM AUTHOR]

To explore the appropriate application of glycemic qualification rate (GQR) calculated by fingerstick blood glucose (BG) monitoring for patients with gestational diabetes mellitus (GDM) by analyzing the relationship between BG control and adverse pregnancy outcomes. Fingerstick Blood Glucose data during the second and third trimester of singleton pregnant women diagnosed with GDM were collected. GQR which is defined as the percentage of fingerstick BG values reaching the targets of BG control in a period of time was calculated. Patients were divided into three groups according to tertiles (tertile 1, GQR <56.25%; tertile 2, GQR 56.25–75%; and tertile 3, GQR ≥75%). Pregnant outcomes were compared among the three groups. Univariate analysis and logistic regression were performed to analyze the potential relationship between GQR and pregnancy outcomes. Receiver operating characteristic (ROC) curves were calculated to determine the cutoff values. We also explored that whether twice or three times monitoring per day would be adequate for GQR calculation, so we brought in two or three glucose measuring times per day to explore the relationship between new GQR and adverse outcomes. A total of 311 patients diagnosed with GDM were analyzed. In univariate analysis, the incidences of cesarean section of tertile 1–3 groups were 61.4%, 58.7%, and 44.9%, respectively (p <.05). The incidences of neonatal hypoglycemia of tertiles 1–3 groups were 19.8%, 18.6%, and 8.7% (p <.05). The difference of composite outcomes was statistically significant (p =.001). After adjustment, the patients with worse BG control (lower GQR) had higher risk of cesarean section (tertile 1 – aOR = 2.029, 1.128–3.648), neonatal hypoglycemia (tertile 1: aOR = 2.498, 1.082–5.766) as well as composite outcomes. The ROC curve of GQR indicated the predictive value for neonatal hypoglycemia (area under the ROC curve (AUC) 0.612 (0.532–0.692)) and neonatal composite outcomes (AUC 0.593 (0.528–0.657)) with optimal cutoff values of 81.1% and 73.5%, respectively. We also explored that whether twice or three times monitoring per day would be adequate for GQR calculation. The result showed that GQR only calculated by FBG + 2hPG after lunch (2h AL) per day also had well relationship with cesarean section (tertile 1: OR = 2.412, 1.322–4.398), neonatal hypoglycemia (tertile 1: aOR = 4.497, 1.607–12.586), and neonatal composite outcomes (tertile 1: aOR = 1.959, 95% confidence interval (CI): 1.114–3.444, p =.020). The GQR calculated by the easily applicable fingerstick BG is related to occurrence of cesarean section and neonatal hypoglycemia in GDM women. GQR ≥ 80% is recommended for better pregnancy outcomes. As for the number of points monitoring per day, GQR calculated by FBG + 2h AL was an optimal option for better pregnancy outcomes if mothers needed to simplify the process of monitoring. [ABSTRACT FROM AUTHOR]

Objective: To compare the rate of neonatal hypoglycemia among newborns delivered by individuals with Type 2 diabetes mellitus (T2DM) in two clinical scenarios: who attempted vaginal delivery vs. had a planned cesarean delivery (CD); who had intrapartum insulin infusion vs. who did not. Methods: This was a retrospective cohort study of individuals with insulin-treated T2DM who had non-anomalous singleton pregnancy and delivered at a single tertiary center (March 2012 and May 2018). Individuals with chronic renal failure, proliferative retinopathy, or major congenital anomalies were excluded. The primary outcome was neonatal hypoglycemia (blood glucose < 40 mg/dl <24 h of age or < 50 mg/dl >24 h of age). Secondary outcomes included neonatal outcomes. Multivariable Poisson regression models with robust error variance were used to examine the association between groups and the primary outcome. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. Results: Of 233 individuals with T2DM, 215 (92.2%) met the inclusion criteria, of whom 95 (44%) attempted vaginal delivery and 120 (56%) had a planned CD. Individuals who labored had a higher gestational age at delivery (36.6 vs. 35.8 weeks, p = .005), and higher blood glucose levels upon admission (125 vs 103, p < .001) compared to those with a planned CD. After adjustment for potential confounders, there was no difference in risk of neonatal hypoglycemia between the groups (41.2 vs 44.1%, aRR 1.05, 95% CI = 0.75-1.45). Among those who attempted vaginal delivery, 34 (35.8%) required insulin infusion. There was no difference in the risk of neonatal hypoglycemia (aRR = 0.79, 95% CI = 0.45-1.37) between newborns delivered by individuals who required insulin infusion and those who did not. Conclusion: Over 40% of newborns delivered by individuals with insulin-dependent T2DM had hypoglycemia; however, there was no significant difference in the risk of hypoglycemia, irrespective of the route of delivery and the use of insulin infusion. [ABSTRACT FROM AUTHOR]

Introduction Evaluate the safety and efficacy of a subcutaneous insulin (SC-I) versus intravenous insulin (IV-I) protocol for optimizing maternal blood glucose levels (BGLs) post-betamethasone administration. Methods Randomized controlled in-patient pilot study in pregnant women with diabetes, excluding type 1 diabetes, receiving betamethasone ≥24 weeks’ gestation. Interventions were stratified SC-I and IV-I protocols, titrated to hourly BGLs (IV-I) or predicted maternal hyperglycemia and 2–4 hourly BGLs (SC-I). Primary outcome was percentage at-target BGL 4.0–8.0 mmol/L over 48 h post-betamethasone. Secondary outcomes were rates of maternal hyperglycemia (>8.0 mmol/L), hypoglycemia (<4.0 mmol/L) and neonatal hypoglycemia (≤2.5 mmol/L). Results 19 women (3 with type 2 diabetes [T2DM], 4 with gestational diabetes [GDM]-diet, 12 GDM-insulin) were randomized to a SC-I (n = 13) or IV-I (n = 6) protocol in a 9-month period. There was a non-significant trend for higher mean percentage at-target BGLs with SC-I vs IV-I (87% vs 81%; p = .055); this was significant when the cohort was restricted to women with GDM (89% vs 81%; p = .04). Maternal hyperglycemia (85% vs 100%; p = .31) and hypoglycemia (54% vs 33%; p = .41) were not significantly different, but there were no BGLs <3.8 mmol/L with IV-I (vs 4 women with SC-I; p = .13). The rate of neonatal hypoglycemia was not different between groups. Conclusion A SC-I or IV-I protocol controls maternal BGLs following betamethasone, but SC-I appears safe and minimizes labor intensive IV-I in GDM. An adequately powered RCT to assess superiority of SC-I is planned. [ABSTRACT FROM AUTHOR]

The prevalence of gestational diabetes parallels the prevalence of type 2 diabetes mellitus and is associated with adverse pregnancy outcomes. However, these data are not available for many parts of the world. We assessed the prevalence of gestational diabetes and pregnancy outcomes in Tajikistan. This cohort study included 2438 consecutively recruited representative pregnant women from 8 locations in two cities in Tajikistan, in whom an oral glucose tolerance test (75 g, fasting, 1 h, 2 h) was performed during gestational weeks 24–28. Women with known diabetes and twin pregnancies were excluded. Associations between glucose tolerance test results and pregnancy outcomes were examined. According to the WHO 2013 thresholds, 32.4% of women qualified as having gestational diabetes, the vast majority (29.7%) based on an elevated fasting glucose level (5.1–5.6 mmol/L), while only 2.8% had elevated 1- or 2-hour values or met more than one threshold. Women with only elevated fasting glucose (impaired gestational fasting glycemia) had no evidence of adverse pregnancy outcomes, while those with elevated 1- and/or 2-hour values (impaired gestational glucose tolerance) had more pregnancy complications (infection of urinary tract 1.8 vs. 8.8% p<0.001; preeclampsia 0.7 vs. 10.3% p<0.001) and emergency cesarean sections (4.4 vs. 13.2% p=0.002). Neonates from pregnancies with impaired gestational glucose tolerance had lower APGARs, lower birth weights, lower 30 min glucose levels, and a lower probability of being discharged alive (all p<0.05). In conclusion, the formal prevalence of gestational diabetes is high in Tajikistan; however, this does not translate into adverse pregnancy outcomes for women with impaired gestational fasting glycemia. [ABSTRACT FROM AUTHOR]

Introduction: Previous reports described a pattern of hypoglycemiainduced damage predominantly affecting the parieto-occipital regions. The long-term neurological sequelae of severe neonatal hypoglycemic encephalopathy include developmental delay, poor head growth, learning or behavioral difficulties, visual impairment, and epilepsy. This study reports neurodevelopmental outcome of children with neonatal hypoglycemia-associated parieto-occipital brain injury who were evaluated in our pediatric neurology outpatient clinic for different neurological complaints. Methods: We retrospectively reviewed patients who were followed at Kocaeli University Hospital, Pediatric Neurology Department between 2007 and 2015. Patients (n=42) with predominately parieto-occipital lesions on magnetic resonance imaging (MRI) with the typical pattern of neonatal hypoglycemia were evaluated. Patients with documented hypoglycemia (n=21) were included in this study. Patients (n=9) with recurrent episodes of hypoglycemia longer than 12 hours were evaluated as prolonged hypoglycemia. Results: Eleven patients (52.4%) experienced seizures in the neonatal period. Eighteen patients (85.7%) developed epilepsy during the followup. Refractory seizures were observed in 8 patients (38.1%). Nine patients (42.9%) manifested microcephaly, seven patients (33.3%) manifested cerebral palsy. Parieto-occipital involvement and the spasticity rate were statistically high in patients with prolonged hypoglycemia (p<0.01). Two patients had autistic features and four patients (19%) had attention deficit hyperactivity disorder. VEP studies could be performed in 18 of 21 patients. All patients had abnormal VEP results. Conclusion: We are of the opinion that most patients of neonatal hypoglycemia are not always documented. Patients under risk and patients with symptoms of hypoglycemia should be vigorously screened and treated to prevent neurologic impairments including cerebral palsy, epilepsy and visual disturbance. [ABSTRACT FROM AUTHOR]

Abstract Background Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. Methods This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. Results Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference − 1; 95% CI − 1 to 0; p

There is limited high-quality data on the best practices for maternal blood glucose management during labor. We compared permissive care (target maternal blood glucose 70–180 mg/dL) to usual care (blood glucose 70–110 mg/dL) among laboring individuals with diabetes. This was a two-site equivalence randomized control trial for individuals with diabetes (pregestational or gestational) at ≥34 weeks in labor. Individuals were randomly allocated to usual care or permissive care. Maternal blood glucose was evaluated by capillary blood glucose monitoring in latent and active labor every 4 and 2 hours. Insulin drip was initiated if maternal blood glucose exceeded the upper bounds of the allocated target. The primary outcome was the first neonatal heel stick glucose within 2 hours of birth before feeding. We assumed a mean first neonatal blood glucose of 50±10 mg/dL. To ensure that the use of permissive care did not increase or decrease the first neonatal blood glucose >10 mg/dL (2-tailed: a=0.05, b=0.1), 96 total participants were required. We calculated adjusted relative risk and 95% confidence intervals in an intention-to-treat analysis. A preplanned Bayesian analysis was used to estimate the probability of equivalence with a neutral informative prior. Of deliveries with diabetes assessed for eligibility (from October 2022 to June 2023), 280 of 511 (54.8%) met eligibility criteria, and 96 of 280 (34.3%) agreed and were randomized. In the usual care group, 17% required an insulin drip compared with none in permissive care. There was equivalence in the primary outcome between usual and permissive care (57.9 vs 57.1 mg/dL; adjusted mean difference, −0.72 [95% confidence interval, −8.87 to 7.43]). Bayesian analysis indicated a 98% posterior probability of the mean difference not being >10 mg/dL. The rate of neonatal hypoglycemia was 25% in the usual care group and 29% in the permissive group (adjusted relative risk, 1.14; 95% confidence interval, 0.60–2.17). There was no difference in other neonatal or maternal outcomes. In this randomized control trial, although almost 1 in 6 individuals with diabetes required an insulin drip with usual intrapartum maternal blood glucose care, permissive care was associated with equivalent neonatal blood glucose. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundThe occurrence of gestational diabetes mellitus (GDM) is caused by a variety of factors and associated with increased risks of several adverse outcomes for both mothers and infants. However, the effects of epidural labor analgesia in parturients with GDM on maternal and infant outcomes have not been characterized.MethodsAccording to parturients' choice, they were divided into the epidural group (n = 133) and no epidural (control) group (n = 135). Data for relative variables in the perinatal period were collected, and the potential associations of epidural labor analgesia with infant outcomes were analyzed by univariate analysis and multivariate logistic regression analyses.ResultsThe rate of neonatal admission to the neonatal intensive care unit (NICU) for hypoglycemia was higher in the epidural group (7.52%) than in the control group (1.48%; P

Background: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. Methods: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. Results: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference − 1; 95% CI − 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. Conclusions: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. Trial registration: www.chictr.org.cn; identifier: ChiCTR-IOR-17011994; registered on 14 July 2017. [ABSTRACT FROM AUTHOR]

Objectives: Cerebro‐placental ratio (CPR) is a doppler tool contributes to clinical decision‐making in pregnancies affected by small for gestational age weight (SGA). Pregnancies affected by gestational diabetes mellitus (GDM) tend to have higher newborn weight, but greater risk of adverse perinatal outcomes. We hypothesized that in GDM‐complicated‐pregnancies CPR will be associated with adverse perinatal outcomes even in the absence of SGA. Methods: This prospective single‐center cohort study included non‐anomalous singleton pregnancies in women with GDM. Those with pre‐pregnancy diabetes mellitus, hypertensive disorder or suspected SGA were excluded. Routine fetal sonographic assessment included CPR—defined as middle cerebral artery pulsatilty index/umbilical artery pulsatilty index. Masked CPR measurement closest to birth was used, classified as >10th (normal) or ≤10th centile (low). Primary outcome was a composite, consisting of stillbirth, Caesarean birth due to abnormal fetal heart rate pattern, 5‐minute Apgar <7, cord arterial pH < 7.0, hypoxic ischemic encephalopathy, or NICU admission >24 hours. Results: Of 281 participants, 24 (8.5%) had low CPR, at a mean gestational age of 36.3 weeks (IQR 34.0–37.4). Birthweight percentile was significantly lower among the low CPR group (35th [IQR 16–31] versus 60th [IQR 31–82]; P =.002). There was no statistically difference in the primary composite outcome between the groups (8.3% versus 7.0%, P =.68). Low CPR was significantly associated with a higher risk of neonatal hypoglycemia (adjusted odds ratio 3.2, 95% CI 1.2–8.3). Conclusion: In pregnancies affected by GDM, CPR ≤10th percentile was not associated with adverse perinatal outcome but was associated with neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

Context: Neonatal hypoglycaemia (NH) is the most common metabolic problem in infants born of mothers with gestational diabetes. Plasma glycated CD59 (pGCD59) is an emerging biomarker that has shown potential in identifying women at risk of developing gestational diabetes. The aim of this study was to assess the association between early maternal levels of pGCD59 and NH. Objective: The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycemia (NH). Methods: This is an observational study of pregnant women with a prepregnancy body mass index (BMI) greater than or equal to 29 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59 were measured in fasting maternal samples taken at the time of a 75-g, 2-hour oral glucose tolerance test performed in early pregnancy (< 20 weeks). NH, the study outcome, was defined as a heel-prick capillary glucose level of less than 2.6 mmol/L within 48 hours of delivery. Results: We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy were positively associated with the prevalence of NH (one-way analysis of variance, P < .001). The odds of NH were higher in infants from mothers in tertile 3 of pGCD59 levels compared to those from mothers in tertile 1 (odds ratio [OR]: 2.41; 95% CI, 1.03-5.63). However, this was attenuated when adjusted for maternal BMI (OR: 2.28; 95% CI, 0.96-5.43). The cross-validated area under the curve (AUC) was 0.64 (95% CI, 0.54-0.74), and adjusted for maternal BMI, age, and ethnicity, the AUC was 0.70 (95% CI, 0.56-0.78). Conclusion: Although pGCD59 levels in early pregnancy in women with BMI greater than or equal to 29 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH. [ABSTRACT FROM AUTHOR]

Background: Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2). Case presentation: We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis. Conclusions: CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes. [ABSTRACT FROM AUTHOR]

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < −1.28 or > 1.28. These categories were compared to Z-score between −1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below −1.28 and above 1.28, respectively, compared with WLR Z-score between −1.28 and 1.28. Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn. [ABSTRACT FROM AUTHOR]

Background: Unlike in developed countries, neonatal morbidity and mortality are the leading challenges associated with easily preventable and treatable disorders during the neonatal period in low- and middle-income countries. However, evidence-based data about prolonged transitional hypoglycemia and associated factors are highly limited in Ethiopia and resource-limited countries., Methods: An institution-based prospective cross-sectional study was conducted at public hospitals in South Gondar in neonatal intensive care units (NICUs). The data were entered and analyzed using SPSS version 23. Descriptive statistics were used to summarize maternal characteristics. Multivariate binary logistic regression at a p value <0.05 was used., Results: A total of 400 neonates, admitted to NICUs in public hospitals within 48-72 h of birth between October 2, 2021, and June 30, 2022, were included in the study. The incidence of prolonged transitional neonatal hypoglycemia (PTHG) was 23.5% (19.3%-28%). The factors associated with PTHG were hypothermia (AOR = 4.41; 95% CI = 2.72-10.92), preterm birth (AOR = 3.5; 95% CI = 1.69-11.97), perinatal asphyxia (AOR = 2.5; 95% CI = 1.34-9.67), and pathological jaundice (AOR = 2.3; 95% CI = 1.21-10.34). In contrast, spontaneous vaginal delivery (SVD) was a protective factor (AOR = 0.72; 95% CI = 0.35-0.88)., Conclusions: The incidence of (PTHG) was nearly one-fifth. Factors increasing the risk of PTHG were hypothermia, preterm birth, perinatal asphyxia (PNA), early onset of sepsis (EONS), and pathological jaundice. Spontaneous vaginal delivery (SVD) was also a protective factor. Preventing neonatal hypothermia was the main measure used to reduce PTHG in the study area. Special attention could be given to neonates with prematurity, early onset neonatal sepsis (EONS), birth asphyxia, and pathological jaundice, as monitoring their RBS could lead to a significant change in reducing PTHG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kebede, Aytenew, Agmas, Asferie and Moges.)

Background: We investigated the impacts of tocolytic agents on maternal and neonatal blood glucose levels in women with gestational diabetes mellitus (GDM) who used tocolytics for preterm labor., Methods: This multi-center, retrospective cohort study included women with GDM who were admitted for preterm labor from twelve hospitals in South Korea. We excluded women with multiple pregnancies, anomalies, overt DM diagnosed before pregnancy or 23 weeks of gestation, and women who received multiple tocolytics. The patients were divided according to the types of tocolytics; atosiban, ritodrine, and nifedipine group. We collected baseline maternal characteristics, pregnancy outcomes, maternal glucose levels during hospitalization, and neonatal glucose levels. We compared the frequency of maternal hyperglycemia and neonatal hypoglycemia among three groups. A multivariate logistic regression analysis was performed to evaluate the contributing factors to the occurrence of maternal hyperglycemia and neonatal hypoglycemia., Results: A total of 128 women were included: 44 (34.4%), 51 (39.8%), and 33 (25.8%) women received atosiban, ritodrine, and nifedipine, respectively. Mean fasting blood glucose (FBG) (112.3, 109.6, and 89.5 mg/dL, P < 0.001) and 2-hour postprandial glucose (PPG2) levels (145.4, 148.3, and 116.5 mg/dL, P = 0.004) were significantly higher in atosiban and ritodrine group than those in nifedipine group. Even after adjusting for covariates including antenatal steroid use, gestational age at admission, and pre-pregnancy body mass index, there was an increased risk of high maternal mean FBG (≥ 95 mg/dL) and PPG2 (≥ 120 mg/dL) levels in the atosiban and ritodrine group than in nifedipine group. The atosiban and ritodrine groups are also at increased risk of neonatal hypoglycemia (< 47 mg/dL) compared to the nifedipine group with the odds ratio of 4.58 and 4.67, respectively ( P < 0.05)., Conclusion: There is an increased risk of maternal hyperglycemia and neonatal hypoglycemia in women with GDM using atosiban and ritodrine tocolytics for preterm labor compared to those using nifedipine., Competing Interests: Hyun Soo Park and Hyun-Joo Seol participated in the Tractocile (atosiban) Advisory Board and received consulting fees from Ferring Pharmaceuticals Korea on October 24, 2023. Other authors have no potential conflicts of interest., (© 2024 The Korean Academy of Medical Sciences.)