Neonatal Hypoglycemia Research Articles

Effect of FSL-CGM on Maternal and Neonatal Outcomes in GDM: A Propensity Score Matching Study in Hangzhou, China.

This study aims to evaluate the impact of using FreeStyle Libre continuous glucose monitoring (FSL-CGM) on maternal glucose control and obstetric and neonatal outcomes among women with gestational diabetes mellitus (GDM). A total of 3062 women with GDM in gestational weeks 24-28 were enrolled in this study and divided into FSL-CGM and self-monitoring of blood glucose (SMBG) groups according to the method of monitoring blood glucose. Nearest-neighbor matching propensity score matching (PSM) was used to balance covariates at a ratio of 1:2. Compared with the first 6days during the study period, the index of glycemic variability, such as the mean largest amplitude of glycemic excursions (LAGE), average daily risk range (ADRR) and glucose management indicators (GMI) during the last 6days were improved (all p < 0.05). The fasting blood glucose before delivery in the FSL-CGM group was lower than that in the SMBG group (p < 0.05). In the normal weight subgroup, the FSL-CGM group had a lower gestational weight gain (GWG) than the SMBG group (p < 0.05). The incidence of neonatal hypoglycemia was higher in the SMBG group than in the FSL-CGM group (p < 0.05). This study demonstrated that FSL-CGM helps reduce maternal glycemic variability and the incidence of neonatal hypoglycemia. Additionally, FSL-CGM may contribute to appropriate gestational weight gain during pregnancy. ClinicalTrials.gov identifier, NCT05003154.

Lactate receptor HCAR1 affects axonal development and contributes to lactate's protection of axons and myelin in experimental neonatal hypoglycemia.

Lactate plays an important role in brain energy metabolism. It contributes to normal brain development and to neuroprotection in diabetic hypoglycemia, but its role in neonatal hypoglycemia is unclear. Moreover, lactate can work as a signaling substance via the lactate receptor HCAR1 (Hydroxycarboxylic acid receptor 1). Recent studies indicate that HCAR1 is protective in mouse models of neonatal hypoxic ischemia and has a role in metabolic regulation in glial cells during hypoglycemia. Here we have studied potential impacts of HCAR1 on axonal and myelin development in the cerebral cortex and corpus callosum of young (p21) wild type (WT) mice and HCAR1 KO mice and in cortical organotypic brain slice cultures. The HCAR1 KO mice showed lower axonal area relative to WT in both cortex and corpus callosum. However, the myelin area was unaffected by HCAR1 KO. Using particle- and colocalization analysis we show that HCAR1 KO predominantly reduces axonal size in unmyelinated axons. Using an organotypic brain slice model of neonatal hypoglycemia, we find that lactate protects both axonal and myelin development in hypoglycemia, partially via HCAR1. Lastly, live imaging with a pH-sensitive dye on acute cortical brain slices indicates that cellular lactate uptake is influenced by HCAR1. In conclusion, our findings support a role of HCAR1 in axonal development and in lactate's protective effects in hypoglycemia.Significance statement Lactate is a critical metabolite for brain energy metabolism, with established roles in neuroprotection and development. Our study provides new insights into the role of the lactate receptor HCAR1 in axonal and myelin development in the neonatal brain. We demonstrate that HCAR1 influences axonal size, particularly in unmyelinated axons, and mediates lactate's protective effects during neonatal hypoglycemia. Using in vivo and ex vivo approaches, including organotypic brain slice cultures and live imaging, we show that HCAR1 influences cellular lactate uptake and protects axonal and myelin integrity under hypoglycemic conditions. These findings highlight the dual role of lactate as an energy substrate and signaling molecule via HCAR1, with implications for understanding brain development and resilience to metabolic stress.

Comparative outcomes of medical and surgical management in children with persistent neonatal hyperinsulinemic hypoglycemia: a focus on long-term growth, metabolic, and developmental implications"

Comparative outcomes of medical and surgical management in children with persistent neonatal hyperinsulinemic hypoglycemia: a focus on long-term growth, metabolic, and developmental implications"

Evaluation of a new guideline for the early detection and management of neonatal hypoglycaemia

Evaluation of a new guideline for the early detection and management of neonatal hypoglycaemia

Developing a congenital hyperinsulinism prioritized research agenda: a patient-driven international collaborative research network

IntroductionCongenital Hyperinsulinism (HI) is a rare disease that causes severe and recurrent hypoglycemia due to dysregulated insulin secretion. HI is the most frequent cause of severe, persistent hypoglycemia in newborns and children. Disease management is focused on preventing the neurological consequences associated with hypoglycemic brain injury; however, treatment is complex, often suboptimal, and places a large burden on families and individuals living with HI. Congenital Hyperinsulinism International (CHI) is an international patient organization that received a grant from the Chan Zuckerberg Initiative to establish the CHI Collaborative Research Network (CRN), a collaborative body to accelerate research for HI.Assessment processStakeholder groups relevant to HI, including individuals living with HI, families, researchers, clinicians, nurses, and industry partners, were identified to join the CRN and work together to create a prioritized research agenda (PRA) to systematically rank research priorities. CRN members worked across 7 workstream groups through a structured process to brainstorm gaps and corresponding solutions to formalize the HI PRA.Actionable recommendationsA total of 362 gaps were identified across research, infrastructure, knowledge, and funding. All groups identified the need for an HI Natural History Study; therefore, this item was identified as a priority that would automatically be placed on the finalized list. Other top gaps identified in the PRA addressed preventing brain damage and the need to increase awareness and understanding related to the role of early and effective diagnosis in preventing brain damage.DiscussionThe formation of the CRN and the development of the PRA have already led to new collaborations, which are fundamental to progress. The PRA process allowed individuals to come to a consensus on the critical needs and to chart short- and long-term approaches to fill the gaps. CRN members continue to meet regularly in working groups focused on special projects to fill gaps identified as high priority by the PRA. Through this active and multidimensional alliance, the CRN is re-imagining the future for people living with HI by improving outcomes through more timely and accurate diagnosis, more effective and less burdensome treatments, more easily obtainable expert care, and better tools to manage HI.

Congenital hyperinsulinemic hypoglycaemia in a neonate: a rare homozygous ABCC8 gene mutation.

Hyperinsulinemic hypoglycaemia (HH) is a heterogeneous disorder causing persistent hypoketotic hypoglycaemia in neonates and infants. Congenital hyperinsulinism (CHI) is a rare cause of HH, resulting from inappropriate insulin secretion by pancreatic β-cells due to genetic defects in key genes, notably ABCC8 and KCNJ11, which encode the SUR1 and Kir6.2 components of the KATP channels, respectively. We present a case of a neonate with congenital HH with persistent hypoglycaemia since birth, which was managed with high-dose glucose infusions, diazoxide and octreotide. A homozygous pathogenic missense variant, c4253G>A (p.Arg1418His) in Exon 35 of the ABCC8 gene was identified in the neonate, confirming CHI. Despite initial refractoriness to treatment, the infant responded to octreotide therapy, cornstarch and careful management with regular feeds and monitoring, avoiding the need for surgical intervention. This case underscores the critical role of genetic diagnosis and timely management in preventing long-term neurological sequelae.

Predictors of Composite Maternal and Fetal Outcomes among Pregnant Women with Early-Onset Type 2 Diabetes: A Cross-Sectional Study.

The most common form of pregestational diabetes in pregnancy is type 2 diabetes, requiring strict metabolic monitoring owing to the risk of adverse pregnancy outcomes. Our study aimed to identify predictors of composite maternal outcome (CMO) and fetal outcome (CFO) separately in pregnant women with early-onset type 2 diabetes (PwEOT2D). The cross-sectional pilot study included 60 PwEOT2D by recording age, socioeconomic determinants, preconception body mass index (pBMI), preconception (pHbA1c) and trimester-specific glycated hemoglobin (HbA1c), gestational weight gain (GWG), and pregnancy outcomes. We defined CMO as at least one of the following: gestational hypertension, preeclampsia, eclampsia, preterm delivery, or emergency section. CFO included at least one of the following: small or large for gestational age, macrosomia, neonatal hypoglycemia, or admission to the neonatal intensive care unit. CMO was detected in 55% and CFO in 35% of PwEOT2D. The majority of PwEOT2D with CMO lived in suburban areas (73.1%), while those without CMO mostly lived in rural areas (51.9%, p = 0.014). Moreover, PwEOT2D with CMO had comparable pBMI to those without CMO (31.45 ± 6.27 versus 28.99 ± 6.28kg/m2, p = 0.136). However, PwEOT2D with CMO had higher pHbA1c (7.28 ± 0.95 versus 6.46 ± 0.96%, p = 0.002) and first trimester HbA1c (7.24 ± 1.08 versus 6.42 ± 0.97%, p = 0.003). Similarly, PwEOT2D with CFO had higher pHbA1c (7.84 ± 0.95 versus 6.41 ± 0.67%, p < 0.001) and first trimester (7.29 ± 1.07 versus 6.65 ± 1.07%, p = 0.032) and second trimester HbA1c (6.45 ± 0.87 versus 5.96 ± 0.82%, p = 0.038). Additionally, GWG was higher in the second (4.38 ± 2.01 versus 3.33 ± 1.61kg, p = 0.032) and third trimester (5.66 ± 2.93 versus 3.89 ± 2.61kg, p = 0.002) compared with those without CMO. Regression analysis identified pHbA1c, first trimester of pregnancy, and community type as predictors of CMO, while pHbA1c and the occurrence of CMO were predictors of CFO. Our results imply that preconception and first trimester of pregnancy HbA1c, as well as community disparities, are predictors of CMO, while the predictors of CFO were only preconception HbA1c and the occurrence of CMO in pregnant women with EOT2D. Therefore, tailoring preventive strategies, followed by achieving and sustaining trimester-specific metabolic control, might improve pregnancy outcomes in women with EOT2D.

Comparison Between Antenatal and Postnatal Colostrum From Women With and Without Type 1 Diabetes.

BackgroundSupplementary feeding, colostrum or, in some countries, commercial milk formula, is given to newborns of women with Type 1 diabetes to prevent neonatal hypoglycemia. Few studies have explored the content of colostrum from women with Type 1 diabetes.Research AimsThis study aimed to investigate the macronutrients in colostrum collected during pregnancy and in the early postpartum period to compare colostrum contents in women with and without Type 1 diabetes.MethodsIn this cohort study, we collected colostrum among 20 women, 10 with and 10 without Type 1 diabetes, at 10 different time points in gestational weeks 36-40 and postpartum Days 1-5. We measured carbohydrates, protein, fat, and kilocalories in colostrum using a human milk analyzer; and we analyzed data using linear mixed models. In a follow-up analysis, we compared the content of colostrum from Day 1 with the nutritional values provided on the commercial milk formula, using a one-sample t test.ResultsThere were no mean differences in carbohydrates (6.6 g/100 ml; 95% CI [6.3, 6.9] vs. 6.7 g/100 ml; 95% CI [6.4, 7.0] p = 0.29); kilocalories (71.1 kcal/100 ml; 95% CI [62.9, 79.3] vs. 85.3 kcal/100 ml; 95% CI [77.2, 93.3] p = 0.21], and fat (2.7 g/100 ml; 95% CI [1.8, 3.6] vs. 2.3 g/100 ml; 95% CI [1.4, 3.2] p = 0.55) in colostrum when comparing women with and without Type 1 diabetes. However, antenatal protein differed at all timepoints tested (p = 0.01). Colostrum macronutrients on Day 1 differed from that of commercial milk formula and all other colostrum time points, except Gestational Week 38.ConclusionsOur study provides insights into antenatal and postnatal colostrum macronutrients among women with and without Type 1 diabetes. Further studies are needed to understand the effects of supplementary feeding using antenatal or postnatal colostrum or commercial milk formula on neonatal hypoglycemia.

Frequency of Hypoglycemia and Hypothermia amongst Newborns Admitted at Pediatrics Emergency of CLF Larkana

Neonatal hypoglycemia is a prevalent metabolic disorder associated with acute neurological issues and long-term developmental complications. Objectives: To assess the frequency of hypoglycemia and hypothermia among newborns admitted to the Neonatal Emergency Department at Child Life Foundation (CLF), Larkana. Methods: The study, conducted from August 15, 2022, to February 15, 2024, involved 200 neonates of both genders in the Neonatal Emergency Department of CLF, SMBBMU, Larkana. Comprehensive demographic and clinical data—including age, gender, delivery mode, birth location, and maternal residence were collected. Axillary temperature was measured using a sterilized thermometer, and capillary glucose was assessed at five intervals (2, 6, 12, 24, and 48 hours’ post-birth) before feeding using an Accu-Chek Glucometer. Results: In a study of 200 newborns, the average age was 3.2 ± 2.4 days, with a mean height of 48.3 ± 7.3 cm, weight of 2.7 ± 0.8 kg, and gestational age of 39.6 ± 6.3 weeks. Most participants were female, and 42.5% were appropriate for gestational age. Cesarean section was the most frequent delivery method (48%). Hypoglycemia occurred in 16% of cases, while hypothermia was more common, affecting 47.5% of newborns. Hypothermia showed significant associations with lower height (p=0.008), weight, gestational age, and cesarean/instrumental deliveries. Hypoglycemia was significantly linked to low birth weight, with gestational age and delivery location showing borderline significance. Gender and age had no notable effects. Data were analyzed using SPSS version 20.0. Conclusions: Hypothermia was more frequent than hypoglycemia among the admitted neonates. Further research is needed to validate and expand on these findings.

Neonatal hypoglycaemia in the offsprings of parents with maturity-onset diabetes of the young (MODY).

Neonatal hypoglycaemia is the most common metabolic disorder of various causes, relatively rare being MODY (Maturity Onset Diabetes of the Young). Data search of relevant articles focused on hypoglycaemia in carriers of selected MODY gene mutations published from 2007 to 2022 was performed in databases Medline, Pubmed, Cochrane and UptoDate basedon key words: 'hyperinsulinemic hypoglycaemia', 'congenital hyperinsulinism', 'MODY', 'HNF4A mutation', 'HNF1A mutation'. Loss of function of HNF4A and HNF1A genes comprises approximately to 5.9 % of diazoxide responsive hyperinsulinemic hypoglycaemia, which may appear in 15 % HNF4A mutation carriers. A typical finding of HNF4A mutation carriers with neonatal hypoglycaemia was a birth weight above 4000 g or above 97th percentile. Although mutations in MODY genes represent a rare cause of neonatal hypoglycaemia, they should be considered in the differential diagnosis, particularly in cases of persistent hypoglycaemia requiring intensivecare.

EFFECT OF MULTIDISCIPLINARY CARE ON NEONATAL OUTCOMES IN HIGH-RISK PREGNANCIES. A SYSTEMATIC REVIEW

Background: High-risk pregnancies are associated with elevated neonatal complications, including preterm birth, low birth weight, and increased neonatal intensive care unit (NICU) admissions. Although traditional obstetric care focuses on maternal monitoring, growing evidence suggests that multidisciplinary care (MDC)—which involves coordinated management by various healthcare specialists—may significantly enhance neonatal outcomes. However, a consolidated analysis of MDC’s impact on neonatal health across different high-risk populations remains limited. Objective: This systematic review aims to evaluate the effectiveness of multidisciplinary care in reducing neonatal complications among women with high-risk pregnancies compared to conventional care models. Methods: A systematic review was conducted following PRISMA guidelines. Electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched for studies published between 2018 and 2024. Keywords included “Multidisciplinary Care,” “High-Risk Pregnancy,” and “Neonatal Outcome.” Eligible studies included randomized controlled trials, cohort studies, and observational studies evaluating neonatal outcomes in the context of MDC. Data extraction and risk of bias assessments were independently performed by two reviewers using standardized tools such as the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale. Results: Eight studies involving over 2,000 high-risk pregnancies were included. MDC was associated with reduced rates of miscarriage, fetal death, neonatal hypoglycemia, macrosomia, and NICU admissions. Several studies reported statistically significant improvements, including a reduction in adverse neonatal outcomes from 60.8% to 3.5% (p&lt;0.001), and improved immunologic and anthropometric neonatal profiles. Overall, MDC models demonstrated superior outcomes compared to routine obstetric care. Conclusion: Multidisciplinary care significantly improves neonatal outcomes in high-risk pregnancies by offering coordinated, patient-centered interventions. Despite promising findings, limitations such as heterogeneity in study designs and sample sizes underscore the need for further large-scale, high-quality trials to refine care protocols and validate effectiveness across broader populations.

Dose-response association between OGTT and adverse perinatal outcomes after IVF treatment: A cohort study based on a twin population.

Investigate the association between Oral Glucose Tolerance Test (OGTT) after in vitro fertilization (IVF) treatment and adverse maternal and neonatal outcomes in twin pregnancies. This retrospective study encompassed 2,541 twin pregnancies conceived through IVF treatment. Adverse maternal and neonatal outcomes were compared across different subgroups based on individual and combined OGTT classifications. A Spearman correlation regression model examined associations between OGTT levels at different time points and parameters such as gestational age, birth weight, and length. Subsequently, a Logistic regression model with restricted cubic splines (RCS) explored the relationships between OGTT levels at different time points and adverse pregnancy outcomes. Ultimately, nine types of machine learning models were developed using OGTT glucose values at different times to predict the risk of adverse pregnancy outcomes. In subgroup analysis based on individual OGTT diagnosis, three time points were examined: fasting glucose (OGTT0), 1-hour post-glucose (OGTT1), and 2-hour post-glucose (OGTT2). OGTT0 ≥ 5.1 mmol/L was significantly associated with increased risks of ICP and neonatal hypoglycemia (p = 0.031; p = 0.022). OGTT1 ≥ 10 mmol/L correlated with higher risks of ICP and neonatal hyperbilirubinemia (p = 0.001; p = 0.002). OGTT2 ≥ 8.5 mmol/L was also linked to neonatal hyperbilirubinemia (p < 0.001). In combined impaired OGTT subgroups, the impaired fasting glucose (IFG) group had a higher incidence of neonatal hypoglycemia than the impaired glucose tolerance (IGT) group and IFG & IGT group, but a lower risk of neonatal hyperbilirubinemia. OGTT2 was negatively correlated with gestational age at delivery (β = - 0.08, p = 0.018), and both OGTT1 and OGTT2 were negatively correlated with neonatal birth weight (β = - 10.54, p = 0.008; β = - 15.04, p < 0.001), as well as OGTT2 with birth length (β = - 0.16, p = 0.009). The RCS logistic regression model indicated that the increase OGTT values was associated with the ICP risk, and the relationship between OGTT2 and neonatal hyperbilirubinemia was U-shaped. Among the various machine learning models predicting adverse outcomes, RandomForest exhibited superior performance. OGTT values in twin pregnancies under IVF treatment are closely linked to adverse maternal and neonatal outcomes, with post-load glucose levels potentially serving as an early biomarker for identifying poorer outcomes. The inflection points in the RCS suggest a new indication point for the association between OGTT and adverse pregnancy outcomes in twin pregnancies conceived through IVF.

Experiences of Pacific parents of infants born at risk of neonatal hypoglycaemia in New Zealand.

Neonatal hypoglycaemia is the primary metabolic disorder affecting newborns. It has severe implications including cerebral injury when left untreated. Pacific newborns have the second-highest prevalence of risk factors for hypoglycaemia amongst all ethnic groups in New Zealand, and therefore disproportionately suffer its effects. However, Pacific voices remain largely unheard regarding experiences with at-risk infants. This qualitative study aims to amplify Pacific families' stories. Nine interviews involving ten participants were transcribed and analyzed. Seven central themes were revealed: Teu Le Vā: Nurturing relationships by healthcare professionals, Complex circumstances, Family decision-making, Talanoa: Culturally congruent information sharing, Cultural beliefs related to medical care in pregnancy, Relevance of faith and spirituality, and Continued follow-up. The findings of this study highlight the pivotal role of healthcare professionals in nurturing Vā or relational space and underscore the necessity of culturally responsive practices to improve Pacific families' experience of neonatal hypoglycaemia care.

Proactive Insulin Escalation for Antenatal Betamethasone-Induced Hyperglycaemia in Women With Diabetes: A Prospective Cohort Study.

In patients with diabetes, antenatal glucocorticoids can induce transient maternal hyperglycaemia for approximately 72 h. This may be associated with adverse outcomes, including neonatal hypoglycaemia, prompting recommendations for prophylactic increases in insulin by some expert groups; however, there are no validated protocols. A review of our institutional practice of empiric dose escalation (Day 1:25%, Day 2-3:40%, Day 4:20%, Day 5:10%) determined it was inadequate to prevent hyperglycaemia. To investigate the efficacy of an intensified insulin escalation protocol in achieving time in target range (3.9-7.8 mmol/L) following antenatal betamethasone. Following implementation of the intensified insulin escalation protocol at Western Health (Day 1 and 2: 50% increase, Day 3:30% increase), a prospective cohort study was conducted for women with gestational diabetes or type 2 diabetes managed with insulin requiring betamethasone. Data was collected from the electronic medical record and expressed as mean ± SD or median (IQR). 29 women (82.8% GDM, 17.2% T2DM) were included with median gestation 33 + 2 (31-34+4) weeks and median BMI 30 kg/m2 (27-38IQR). In the 72 h post first-dose betamethasone, the proportion of readings in target range (< 5.1 mmol/L fasting and < 6.8 mmol/L post prandial) was 35.3%. There was no maternal hypoglycaemia. Median increase in insulin requirement was 50% (22.6%-100% IQR) on Day 1, 106% on Day 2 (33%-297% IQR) and 133% on Day 3 (23%-543% IQR). A significant increase in insulin requirement, exceeding current guideline recommendations, occurs following antenatal betamethasone in women with diabetes, and further prospective evaluation of optimal dosing is required.

Experiences of whānau Māori with pēpi at risk of neonatal hypoglycaemia: A qualitative study.

Neonatal hypoglycaemia can cause substantial morbidity and mortality. Pēpi Māori (Indigenous infants from Aotearoa New Zealand) are at increased risk. This study explored the lived experience of whānau (extended family kinship groups) Māori having a pēpi at risk of hypoglycaemia. Whānau Māori collectives were interviewed, and transcripts analysed using NVivo software and the Reflexive Thematic Analysis. There were 11 participants (10 whānau collectives; 10 Māmā (mothers) and one Pāpā (father)). The overarching concept of Pā Harakeke (flax bush) framed three superordinate themes, each with subordinate themes. Themes were Whānau, (desire to do the best for pēpi, whakapapa (geneology), collective decision making and whānau led solutions), Shifting the narrative (whānau as part of the team, communication, mana motuhake (self-determination), fully informed) and Health system (colonial health structures, navigation, racism and tikanga (customs)). Whānau Māori narratives provided insight into opportunities for optimising care for those with pēpi at risk of neonatal hypoglycaemia.

Hypoglycemia Incidence in Newborns Identified to Be at Risk, Data from a Tertiary Care Hospital in Turkey.

Neonatal hypoglycemia (NH) is one of the most prevalent neonatal problems. We aimed to describe frequency and patterns of NH in neonates at risk of hypoglycemia. In this single-center retrospective descriptive cross-sectional study, the incidence of hypoglycemia in newborns at risk of NH born at Mersin University Hospital between Jan 2017 and Jan 2023, was investigated. The blood glucose level being lower than 40 mg/dL was defined as NH. Overall, 506 neonates at risk of hypoglycemia were included: 53 SGA infants (10.5%), 127 LGA infants (25.1%), 212 infants of diabetic mothers (41.9%), and 230 late preterm infants (45.5%). Hypoglycemia developed in 113 out of 506 at-risk newborns (22.3%). Symptomatic hypoglycemia developed in nine infants (1.8%), while asymptomatic hypoglycemia developed in 104 infants (20.5%). Recurrent hypoglycemia incidence was 4.2%. Severe hypoglycemia developed in 13 infants (2.6%). All symptomatic hypoglycemic infants and 8 asymptomatic hypoglycemic infants requiring IV glucose, 17 infants (17/506, 3.4%), were hospitalized in the NICU. The targeted blood glucose level was reached in 1 hour at the latest in all hypoglycemic infants. With the algorithm applied, we did not see recurrent hypoglycemia after the first day of life in risky newborns, and we reached the targeted glucose values in hypoglycemic newborns within the desired period.

Three is Better Than Two:Dose-related Efficacy of Dextrose Gel for Neonatal Hypoglycemia in At-Risk Infants, a Quality Improvement Initiative.

Using a quality improvement (QI) framework, we aimed to use dextrose gel (DG) to reduce admissions for neonatal hypoglycemia by 20% and IV dextrose fluid needs by 10% in at-risk infants. This is a prospective QI study using the Model for Improvement and planned sequential experimentation through three Plan-Do-Study-Act (PDSA) cycles: pathway creation, EMR implementation, and dose increase. Data were analyzed using Shewhart P-charts and chi-square tests. Our interventions increased the percentage of at-risk infants with hypoglycemia who received DG from 67% to 98%. Implementing three doses of DG caused a special cause variation, reducing neonatal hypoglycemia admissions from 3.7% to 2.0% and IV dextrose fluid rates from 2.7% to 1.7% (46% and 37% reduction, respectively). Three doses of dextrose gel administered to at-risk infants with neonatal hypoglycemia reduced the need for additional intervention, suggesting the dose-related efficacy of dextrose gel in mitigating the consequences of neonatal hypoglycemia.

Pregnancy and postpartum cardiometabolic outcomes among women with overt diabetes compared to women with normoglycaemia, gestational diabetes and pre-existing diabetes: A systematic review and meta-analysis.

Overt diabetes in pregnancy (ODiP) is a condition identified by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) in 2010. Despite the clinical significance, our knowledge regarding its impact during pregnancy and the postpartum period is limited due to small sample sizes in previous studies. This systematic review and meta-analysis (SRM) aimed to consolidate evidence on outcomes in the pregnancy and postpartum period among women with ODiP in comparison to women with gestational diabetes mellitus (GDM), pre-existing diabetes (PED) and normoglycaemia. A comprehensive search was conducted across PubMed, Embase and Scopus for relevant studies published from January 1, 2010, to May 31, 2024. Eleven studies, including data from 16 135 pregnancies, were analysed. Women with ODiP had a significantly higher risk of gestational hypertension (RR 1.93; 95% CI 1.45, 2.58), pre-eclampsia (RR 1.65; 95% CI 1.26, 2.16) and caesarean delivery (RR 1.14; 95% CI 1.01, 1.29) compared with GDM. Adverse neonatal outcomes such as large for gestational age (RR 1.45; 95% CI 1.13, 1.85), macrosomia (RR 1.66; 95% CI 1.05, 2.64), neonatal hypoglycaemia (RR 1.52; 95% CI 1.06, 2.19) and stillbirth (RR 4.30; 95% CI 1.69, 10.98) were also significantly higher than GDM. The risk of postpartum diabetes was 6 times higher than in women with GDM and 25 times higher than in women with normoglycaemia. Variations in diagnostic criteria and postpartum follow-up duration contributed to heterogeneity. This SRM demonstrates that ODiP is associated with significantly worse pregnancy and postpartum outcomes compared with GDM and normoglycaemia in pregnancy. These findings underscore the need for targeted clinical strategies to manage ODiP and mitigate adverse maternal and neonatal outcomes.

Iatrogenic Fetal Hypoglycemia Following Tight Peripartum Glucose Control in Diabetic Mothers: A Hypothesis and a Case Report

AbstractCurrent management of diabetes in pregnancy includes prompt normalization of glucose prior to delivery in women with poorly controlled diabetes. While the benefits of glucose control throughout pregnancy are well-documented, the benefits of rapid glucose normalization prior to delivery are borderline. There is a lack of information on the fetal effects of this practice. There is a concern that a rapid decrease in maternal glucose level could cause hypoglycemia in the fetus, developing in the same manner as in a newborn infant of a mother with diabetes.This case highlights a 37 week infant of a mother with poorly controlled diabetes, whose mother's glucose was normalized with intravenous insulin 24 hours before delivery. The infant's arterial cord blood glucose was 2.1 mmol/L, indicative of hypoglycemia, and it required neonatal intensive care unit admission. Current guidelines emphasize tight peripartum glycemic control but overlook potential fetal hypoglycemia before birth. This case suggests fetal hypoglycemia may precede neonatal hypoglycemia, with similar risks but limited diagnostic opportunities. Further research is needed to evaluate fetal outcomes of stringent glycemic control and to establish early cord blood glucose monitoring to improve the identification and management of hypoglycemia in this vulnerable population.

The genetics of low and high birthweight and their relationship with cardiometabolic disease.

Low birthweight infants are at increased risk not only of mortality, but also of type 2 diabetes mellitus and CVD in later life. At the opposite end of the spectrum, high birthweight infants have increased risk of birth complications, such as shoulder dystocia, neonatal hypoglycaemia and obesity, and similarly increased risk of type 2 diabetes mellitus and CVD. However, previous genome-wide association studies (GWAS) of birthweight in the UK Biobank have primarily focused on individuals within the 'normal' range and have excluded individuals with high and low birthweight (<2.5 kg or >4.5 kg). The aim of this study was to investigate genetic variation associated within the tail ends of the birthweight distribution, to: (1) see whether the genetic factors operating in these regions were different from those that explained variation in birthweight within the normal range; (2) explore the genetic correlation between extremes of birthweight and cardiometabolic disease; and (3) investigate whether analysing the full distribution of birthweight values, including the extremes, improved the ability to detect genuine loci in GWAS. We performed case-control GWAS analysis of low (<2.5 kg) and high (>4.5 kg) birthweight in the UK Biobank using REGENIE software (Nlow=20,947; Nhigh=12,715; Ncontrols=207,506) and conducted three continuous GWAS of birthweight, one including the full range of birthweights, one involving a truncated GWAS including only individuals with birthweights between 2.5 and 4.5 kg and a third GWAS that winsorised birthweight values <2.5 kg and >4.5 kg. Additionally, we performed bivariate linkage disequilibrium (LD) score regression to estimate the genetic correlation between low/normal/high birthweight and cardiometabolic traits. Bivariate LD score regression analyses suggested that high birthweight had a mostly similar genetic aetiology to birthweight within the normal range (genetic correlation coefficient [rG]=0.91, 95% CI 0.83, 0.99), whereas there was more evidence for a separate set of genes underlying low birthweight (rG=-0.74, 95% CI 0.66, 0.82). Low birthweight was also significantly positively genetically correlated with most cardiometabolic traits and diseases we examined, whereas high birthweight was mostly positively genetically correlated with adiposity and anthropometric-related traits. The winsorisation strategy performed best in terms of locus detection, with the number of independent genome-wide significant associations (p<5×10-8) increasing from 120 genetic variants at 94 loci in the truncated GWAS to 270 genetic variants at 178 loci, including 27 variants at 25 loci that had not been identified in previous birthweight GWAS. This included a novel low-frequency missense variant in the ABCC8 gene, a gene known to be involved in congenital hyperinsulinism, neonatal diabetes mellitus and MODY, that was estimated to be responsible for a 170 g increase in birthweight amongst carriers. Our results underscore the importance of genetic factors in the genesis of the phenotypic correlation between birthweight and cardiometabolic traits and diseases.