Maternal Hemoglobin A1c in the Third-Trimester May Underestimate Maternal Hyperglycemia and Its Impact on Offspring in Perinatal Demise Associated With Gestational Diabetes Mellitus: An Autopsy Case Series.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common metabolic disorder linked to adverse pregnancy outcomes. Recent research indicates that HbA1c is reliable in detecting maternal glycemia during the first trimester but may underestimate glucose intolerance in the late second to third trimesters. Therefore, it is reasonable to hypothesize that mothers with GDM, despite apparently normal HbA1c levels in the third trimester, may give birth to infants displaying characteristic features often seen in infants of diabetic mothers with suboptimal glycemic control. This study aimed to describe a case series of autopsy cases involving stillborn or deceased neonates delivered in the third trimester to mothers diagnosed with GDM and having normal HbA1c levels at or around the time of delivery. The primary focus was on identifying and documenting the characteristic features commonly associated with "infants of diabetic mothers" with suboptimal glycemic control in this series of cases. MATERIALS AND METHODS: We conducted a retrospective review of autopsy reports from our institution spanning 7.5 years. The study included cases that met the following criteria: (1) stillborn or infants who died in the early neonatal period, delivered in the third trimester; (2) mothers diagnosed with GDM; (3) normal maternal HbA1c levels of ≤6.1% at or around the time of delivery; (4) birthweight or femoral length exceeding the 90th percentile for gestational age; and (5) absence of genetic aberrations. We also examined these cases for other characteristic features associated with "infants of diabetic mothers." RESULTS: Ten autopsy cases met our inclusion criteria, including 9 stillbirths and 1 neonatal death. Gestational age at delivery ranged from 32 to 39 weeks (mean: 35.7 weeks). Femoral length exceeded the 90th percentile in all cases, and 6 cases had birthweights above the 90th percentile. Puffy facies were observed in 6 cases. Among the 9 cases with complete autopsies including internal examination, 6 exhibited excess adipose tissue, 4 had cardiomegaly, and 3 showed pancreatic islet hyperplasia. Hypoxic-ischemic encephalopathy was detected in 7 cases. No structural abnormalities were noted. DISCUSSION: Our findings demonstrated that fetuses and neonates born to mothers with apparently normal HbA1c levels in the third trimester could still display characteristic features commonly observed in infants of diabetic mothers with poor glycemic control, also known as "infants of diabetic mothers." This study underscores the potential of third-trimester maternal HbA1c measurements to underestimate maternal glycemia and its consequential impact on fetal development, as well as the subsequent manifestation of features of "infants of diabetic mothers."

Maternal and neonatal outcomes in mothers with diabetes mellitus in qatari population.

BACKGROUND: Diabetes Mellitus (DM) is a major cause of maternal, fetal, and neonatal morbidities. Our objective was to estimate the effect of both pre-pregnancy and gestational DM on the growth parameters of newborns in the Qatari population. METHODS: In this population-based cohort study, we compared the data of neonates born to Qatari women with both pre-pregnancy and gestational diabetes mellitus in 2017 with neonates of healthy non-diabetic Qatari women. RESULTS: Out of a total of 17020 live births in 2017, 5195 newborns were born to Qatari women. Of these, 1260 were born to women with GDM, 152 were born to women with pre-pregnancy DM and 3783 neonates were born to healthy non-diabetic (control) women. The prevalence of GDM in the Qatari population in 2017 was 24.25%. HbA1C% before delivery was significantly higher in women with pre-pregnancy DM (mean 6.19 ± 1.15) compared to those with GDM (mean 5.28 ± 0.43) (P <0.0001). The mean birth weight in grams was 3066.01 ± 603.42 in the control group compared to 3156.73 ± 577.88 in infants born to women with GDM and 3048.78 ± 677.98 in infants born to women with pre-pregnancy DM (P <0.0001). There was no statistically significant difference regarding the mean length (P= 0.080), head circumference (P= 0.514), and rate of major congenital malformations (P= 0.211). Macrosomia (Birth weight > 4000 gm) was observed in 2.7% of the control group compared to 4.8% in infants born to women with GDM, and 4.6% in infants born to women with pre-pregnancy DM (P= 0.001). Multivariate logistic regression analysis demonstrated that higher maternal age (adjusted OR 2.21, 95% CI 1.93, 2.52, P<0.0001), obesity before pregnancy (adjusted OR 1.71, 95% CI 1.30, 2.23, P<0.0001), type of delivery C-section (adjusted OR 1.25, 95% CI 1.09, 1.44, P=0.002), and body weight to gestational age LGA (adjusted OR 2.30, 95% CI 1.64, 2.34, P<0.0001) were significantly associated with increased risk of GDM. CONCLUSION: Despite the multi-disciplinary antenatal diabetic care management, there is still an increased birth weight and an increased prevalence of macrosomia among the infants of diabetic mothers. More efforts should be addressed to improve the known modifiable factors such as women's adherence to the diabetic control program. Furthermore, pre-pregnancy BMI was found to be significantly associated with gestational DM, and this is a factor that can be addressed during pre-conceptional counseling.

Is Routine Monitoring for Hypoglycemia Required in Intramural Asymptomatic Infant of Diabetic Mother? An Audit in a Tertiary Care Hospital.

AIMS: This retrospective audit aimed to analyze whether routine frequent monitoring for hypoglycemia is required in asymptomatic infant of diabetic mother born in tertiary care hospital. METHODS: The study analyzed the blood sugar level of 196 infants of diabetic mothers. RESULTS: The overall incidence of hypoglycemia from 196 study participants was 9.18% (N = 18). The incidence of hypoglycemia at 2 h of life was maximum (83.33%) and it was significant when compared to 3, 6, 9 and 12 h (p < 0.0001). Blood glucose levels were significantly more at 6 (p = 0.0002)), 9 (p = 0.0001) and 12 h (p = 0.0001) when compared to glucose level at 2 h except at 3 h of life (p = 0.062). Similarly blood glucose at 9 (p = 0.0001) and 12 h of life (p = 0.0002) were significantly more than at 3 h of life. Blood glucose at 9 h was significantly more than at 6 h of life (0.032) and at 12 hours of life (p = 0.0237) was significantly higher than at 6 h of life. CONCLUSION: The frequent blood glucose monitoring for hypoglycemia in infant of diabetic mother as per American Academy of Pediatrics may be reduced as per the findings in our study. However, this needs to be confirmed by a properly designed observational study/adequately powered randomized controlled trial.

Subclinical Decrease in Myocardial Function in Asymptomatic Infants of Diabetic Mothers: A Tissue Doppler Study.

Infants of diabetic mothers (IDMs) with hypertrophic cardiomyopathy are recognized to have impaired myocardial performance, but less is known about ventricular function in IDMs without hypertrophy. We hypothesized that in asymptomatic newborns with normal two-dimensional echocardiographic evaluations, pulsed wave tissue Doppler imaging (TDI) would suggest a subclinical decrease in the cardiac function of IDMs compared to infants of non-diabetics (nIDMs). This is a retrospective cohort study of asymptomatic neonates ≥36 weeks gestation, at 0-7 days of life, with normal standard echocardiograms. Systolic (S'), early diastolic (E'), and late diastolic (A') TDI velocities were measured at the mitral valve (MV) annulus, basal interventricular septum (IVS), and tricuspid valve (TV) annulus, and averaged from three consecutive cardiac cycles. Demographic, perinatal, and echocardiographic variables were compared between IDM and nIDM groups. Of 631 subjects, 75 IDMs were identified. The mean gestational age of the entire cohort was 39.33 weeks (±1.26), birth weight 3.44 kg (±0.56), and body surface area (BSA) 0.21 m2 (±0.02). IDMs had significantly greater birth weight and BSA, lower gestational age, older maternal age, and higher incidence of maternal obesity and hypertension than nIDMs (p < 0.001). On multivariable analysis, IDMs had significantly lower S' (p ≤ 0.03) and E' (p < 0.001) velocities, and higher E/E' ratios (p < 0.001) at the MV, IVS, and TV than nIDMs. In asymptomatic newborn IDMs without cardiac hypertrophy, pulsed wave TDI suggests a subclinical decrease in systolic and diastolic myocardial function compared to nIDMs.

Troponin T and NT ProBNP Levels in Gestational, Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants.

This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24-72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p < 0.001). NT proBNP levels were positively correlated with interventricular septum thickness in the pregestational and gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p < 0.01). Both pregestational and gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (<6.1 %) and suboptimal (>6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p < 0.01). In the suboptimal metabolic control diabetic group, NT proBNP was only found to be positively correlated with the left ventricular mass index (r = 0.586, p < 0.01). While there was no correlation in the myocardial performance index between infants of diabetic mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.

A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network.

BACKGROUND: Neonatal hypoglycaemia is a common problem linked to both brain damage and death. There is controversy regarding both the definition of and best treatment for neonatal hypoglycaemia. AIM: To determine current management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Four questionnaires were sent to the Director of each of the 45 nurseries within the ANZNN. The Director was asked to complete one questionnaire and give the remaining three to other doctors involved with the management of babies with hypoglycaemia in the nursery. RESULTS: One hundred and eighty surveys were sent and 127 were returned (71%), including at least one from each nursery. Almost all respondents (120, 94%) reported using a protocol to treat hypoglycaemia. Only 2 (2%) reported screening all babies for neonatal hypoglycaemia, with the remainder screening babies at risk. Only 67, (53%) reported that blood glucose levels were tested on an analyser generally considered to be reliable at low levels. Most respondents (99, 78%) reported the clinical threshold for treatment was <2.6 mmol/L. However, when provided with clinical scenarios, respondents reported a variety of interventions, including no treatment. CONCLUSION: Doctors within the ANZNN are consistent about definition and screening for neonatal hypoglycaemia. However, frequently, the diagnosis is made using unreliable analysers. There is also wide variation in treatment, suggesting a lack of reliable evidence on which to base practice.

Association of Umbilical Cord Perilipin 2 Levels with Neonatal Anthropometric Measurements in Infants of Diabetic Mothers.

BACKGROUND: Perilipin 2 (PLIN2) is a protein that contributes to the formation and stability of lipid droplets. It has been associated with the development of several diseases, particularly related to glucose and lipid metabolism. In infants of diabetic mother (IDM), fetal hyperinsulinaemia leads to increased adipose tissue and macrosomia. The aim of this study was to investigate the relationship between PLIN2 levels and anthropometric measurements in the IDM and to investigate the relationship between PLIN2 levels and IGF-1, IGF-2 and leptin levels. METHODS: The study group consisted of IDMs, while the control group consisted of infants born to non-diabetic mother, matched for gestational week and gender. Cord blood samples were collected from all patients to determine PLIN2, IGF-1, IGF-2 and leptin levels. Anthropometric measurements were taken for all patients at birth. RESULTS: There were no differences between the groups in birth weight, birth length, head circumference and body mass index (BMI), but middle arm circumference, triceps, biceps, subscapular and suprailiac skinfold thickness were significantly higher in the IDM. While PLIN2, IGF-1, IGF-2 and leptin levels were similar between groups, there was a strong correlation between PLIN2 levels and IGF-2 and leptin levels. CONCLUSIONS: Even if IDMs were not macrosomic, the presence of high subcutaneous adipose tissue was not associated with PLIN2.

The effect of maternal weight on neonatal cardiac functions following diabetic and non-diabetic pregnancies.

OBJECTIVE: We aimed to study myocardial functions of infants appropriate and large for gestational age (IDM-AGA, IDM-LGA) of diabetic mothers (IDM) and AGA and LGA infants of non-diabetic mothers comparatively. METHODS: Newborns were assessed between 24 and 72 h. M-Mode, pulsed wave, and tissue Doppler echocardiography were performed. RESULTS: A negative correlation was found between shortening fraction and maternal weight at delivery in the LGA group (p=0.009, r=-0.58). E/Early diastolic (E') ratio and deceleration time were increased in IDM-AGA than AGA group (p=0.02, p=0.02). There was a negative correlation between maternal blood glucose and E/A ratio (p=0.015 r=-0.63), a positive correlation between maternal blood glucose and mitral A, late diastolic (A') wave in IDM-AGA (p=0.014 r=0.63, p=0.016 r=0.62). Maternal weight gain during pregnancy was in correlation with measured and tei index in IDM-AGA group (p=0.008 r=0.72). Maternal age, pre-pregnancy weight, and weight at delivery and mitral E were higher in IDM-LGA group than IDM-AGA (p=0.03, p=0.01, p=0.003, p=0.012). CONCLUSION: We found that maternal weight has a negative effect on myocardial function in LGA newborns. Diastolic functions were found impaired in IDM-AGA infants and in infants of mothers with high blood glucose. Maternal weight gain during pregnancy has a negative effect on myocardial functions.

Effectiveness of hospital-based oral dextrose gel in prevention and treatment of asymptomatic newborns at risk of hypoglycemia.

OBJECTIVE: To evaluate the effectiveness of using hospital-based 40% dextrose gel (DG) in preventing and treating asymptomatic hypoglycemia in infants of diabetic mothers (IDM), large for gestational age (LGA), and macrosomic neonates. METHODS: A medical chart review was conducted to compare data between before (April 2018 to March 2019, epoch 1) and after (September 2020 to November 2021, epoch 2) 40% DG implementation. DG, prepared by the hospital pharmaceutical unit, was applied within 30-45 min after birth, and three additional doses could be repeated during the first 6 h of life in combination with early feeding. The primary outcome was the rate of intravenous dextrose administration. Secondary outcomes were the incidence of hypoglycemia, first capillary blood glucose concentrations, and the length of hospital stay. RESULTS: Six hundred forty-three at-risk newborns were included (320 before and 323 after implementation of DG). Maternal and neonatal baseline characteristics were not different between the two epochs. The incidence of hypoglycemia was not different (17.8% in before versus 14.6% in after implementation, p = 0.26). The rate of intravenous dextrose administration after DG implementation was significantly lower than that before DG implementation (3.4% versus 10.3%, p < 0.001, risk reduction ratio = 0.33, 95% CI = 0.17-0.64). The length of hospital stay was not different between the two epochs. CONCLUSIONS: Implementing a protocol for administration of hospital-based 40% DG can reduce the need of intravenous dextrose administration among IDM, LGA and macrosomic neonates.

Role of cord blood IGF-1 and maternal HbA1c levels to predict interventricular septal hypertrophy among infants of diabetic mothers: A case-control study.

BACKGROUND: Infants of diabetic mothers (IDMs) develop interventricular septal hypertrophy (ISH) (> 6 mm) [1]. The proportion of IDMs developing ISH varies from country to country. Maternal HbA1c and cord blood Insulin-like growth factor-1 (IGF-1) levels have been found useful to predict ISH. METHODS: This was a case-control study of term neonates of diabetic mothers (cases) and of non-diabetic mothers (controls) to evaluate echocardiographic (ECHO) differences among cases and controls and to find the correlation of interventricular septal thickness (IVS) thickness with maternal HbA1C and cord blood IGF-1 levels. RESULTS: Of 32 cases and 34 controls (mean gestational age 37.7 ± 0.9 weeks), 15 (46.8 %) cases, no control developed ISH. Septal thickness was more (6 ± 0.15 cm vs 3 ± 0.06 cm; p = 0.027) in cases than controls. Functional ECHO parameters including left ventricle ejection fraction were comparable (p = 0.9) among the two groups. Maternal HbA1C levels were higher (6.5 % ± 1.3 vs 3.6 % ± 0.7; p = 0.001) with a positive correlation with IVS (Pearson's coefficient 0.784, p < 0.001). Cord blood IGF1 levels were too higher in cases (99.1 ± 6.09 ng/ml vs 37.1 ± 2.99 ng/ml; p < 0.001) with moderate correlation with IVS thickness (Pearson's coefficient 0.402; p = 0.00). Receiver operator curve analysis showed, that at a cut-off of 72 ng/ml, cord blood IGF1 predicted ISH with 72 % sensitivity; 88 % specificity and at a cut-off of 7.35 %, maternal HbA1c predicted ISH with sensitivity; specificity of 93.8 % and 72.1 % respectively. CONCLUSION: ISH was present in 46.8 % in cases as compared to none in controls. IVS thickness correlated well with maternal HbA1C and moderately with cord blood IGF-1 levels. Functional parameters on ECHO were unaffected by maternal diabetic control. At the cut-off of maternal HbA1c of 7.35 % and cord blood IGF-1 of 72 ng /ml, babies need to be monitored clinically with ECHO to look for ISH.

Clinical usefulness of glycated albumin and glycated albumin-to-glycated hemoglobin ratio of gestational diabetes mellitus in late pregnancy for predicting infant complications.

BACKGROUND: Gestational diabetes mellitus (GDM) with poorly controlled glycemia is associated with poor pregnancy outcomes. However, adequate markers for glycemic control in GDM have not been fully evaluated. METHODS: We retrospectively studied 77 patients with GDM and their infants. Mean glycated albumin (GA), glycated hemoglobin (HbA1c), and GA/HbA1c in GDM were compared between two groups stratified by the presence or absence of infant complications (complications or non-complications). We assessed the predictability of infant complications in GA, HbA1c, and GA/HbA1c of women with GDM by receiver operating characteristic analysis (ROC). RESULTS: In complications and non-complications, GA and GA/HbA1c were significantly associated with neonatal hypoglycemia (13.9% vs. 13.0%, p < 0.001 and 2.49 vs. 2.33, p < 0.001, respectively), respiratory disorders (13.7% vs. 13.2%, p = 0.013 and 2.48 vs. 2.34, p < 0.001, respectively), myocardial hypertrophy (14.5% vs. 13.0%, p < 0.001 and 2.59 vs. 2.33, p < 0.001, respectively), and large for gestational age (14.5% vs. 13.1%, p < 0.001 and 2.58 vs. 2.34, p < 0.001, respectively). Compared with each infant complication in ROC, GA and GA/HbA1c had higher area under the curve than HbA1c. Especially, GA and GA/HbA1c had highest AUC in predicting myocardial hypertrophy and large for gestational age (GA; 0.92 and 0.92, GA/HbA1c; 0.91 and 0.86, respectively). Although statistically significant positive correlations were found between GA and GA/HbA1c and the number of infant complications (GA: r = 0.417, p < 0.001; GA/HbA1c: r = 0.408, p < 0.001), their correlations were weak. CONCLUSION: Compared with HbA1c, GA and GA/HbA1c of GDM in late pregnancy might be useful for predicting infant complications arising from GDM.

Socioeconomic and racial disparities in the prevalence of congenital heart disease in infants of diabetic mothers.

Infants of diabetic mothers (IDM) are at increased risk for congenital heart disease (CHD). There is little information in the literature about the impact of economic status and race/ethnicity on the prevalence of CHD in IDM. Using the KID national database collected from 2003 to 2012, we studied over 180,000 IDM to compare the prevalence of CHD according to family income and race/ethnicity. There were 9214 (5.02%) CHDs out of 183 453 IDM. We found significant impact of family income and race/ethnicity on the prevalence of CHD. Specifically, compared to IDM born in a family with highest 25th quartile family income, infants in the lowest 25th quartile family income had higher odds of CHD with unadjusted odds ratio (OR) of 1.6 [(95% confidence interval (CI): 1.4-1.7), p < .001]. In terms of racial/ethnic differences, Black [unadjusted OR = 1.4 (95% CI: 1.3-1.5), p < .001] and Hispanic [unadjusted OR 1.26 (95% CI: 1.2-1.4), p < .001] IDM are more likely, and Asians [0.69 (95% CI: 0.59-0.81), p < .001] were less likely to have CHD when compared to whites. When adjusting race/ethnicity for family income quartile and vice versa, we did not observe changes in the estimates, suggesting that family income and race/ethnicity impact on the odds of CHD independently. Our report of higher prevalence of CHD among IDM in ethnic minorities and lower socioeconomic status would warrant more studies to further dissect causes of higher prevalence in these subpopulations.

The Term Newborn: Hypoglycemia.

This review provides an update on neonatal hypoglycemia in the term infant, including discussion of glucose metabolism, definitions of hypoglycemia, identification of infants commonly at risk, and the screening, treatment, and potential neurologic outcomes of postnatal hypoglycemia. Neonatal hypoglycemia is a common metabolic condition that continues to plague clinicians because there is no clear relationship between low glucose concentrations or their duration that determines adverse neurologic outcomes. However, severely low, prolonged, recurrent low glucose concentrations in infants who also have marked symptoms such as seizures, flaccid hypotonia with apnea, and coma clearly are associated with permanent brain damage. Early identification of at-risk infants, early and continued breastfeeding augmented with oral dextrose gel, monitoring prefeed glucose concentrations, treating symptomatic infants who have very low and recurrent low glucose concentrations, and identifying and aggressively managing infants with persistent hyperinsulinemia and metabolic defects may help prevent neuronal injury.

Infant of diabetic mother: what one needs to know?

The global incidence of diabetes mellitus, including diabetes in pregnant women, is on the rise. Diabetes mellitus in a pregnant woman jeopardizes not only maternal health but can also have significant implications on the child to be born. Therefore, timely diagnosis and strict glycemic control are of utmost importance in achieving a safe outcome for both the mother and fetus. The treating physician should be aware of the complications that can arise due to poor glycemic control during pregnancy. The objective of this article is to discuss the key concerns in a neonate born to diabetic mother, the underlying pathogenesis, and the screening schedule during pregnancy.

Hearing outcomes in children of diabetic pregnancies.

OBJECTIVE: Children of diabetic pregnancies (CDPs) face numerous risk factors for hearing loss (HL). The objective of this study was to investigate the hearing outcomes of CDPs on a population scale. METHODS: Using the Audiological and Genetic Database, the prevalence, severity, and progression of HL in CDPs was compared against children of non-diabetic pregnancies (CNDPs) who served as controls. RESULTS: Among 311 CDPs, 71.1% demonstrated evidence of HL compared to 45.5% in CNDPs (p < 0.001). The mean age at which CDPs received audiograms was 3.6 years compared to 5.4 years for CNDPs (p < 0.001). Compared to CNDPs, CDPs were similarly affected by common otologic conditions such as acute otitis media (25.7%), chronic otitis media (38.3%), and Eustachian tube dysfunction (41.8%) (all p > 0.05). CDPs were more likely to have bilateral HL (81%) and sensorineural hearing loss (SNHL) (8%) relative to CNDPs (p < 0.001 and p = 0.004, respectively). Rates of conductive HL and mixed HL were not significantly different between groups (p = 0.952 and p = 0.058, respectively). CDPs were at significant risk for the development of HL (aOR 1.66 [1.28-2.17], SNHL (aOR 1.63 [1.01-2.52], and high-frequency HL (aOR 1.32 [1.03-1.68]). Of the comorbidities evaluated, CDPs with hyperbilirubinemia (aOR 1.85 [1.18-2.84]), perinatal asphyxia (aOR 1.90 [1.06-3.16]), or congenital heart disease (aOR 1.21 [1.07-1.37]) demonstrated higher risk of SNHL. CONCLUSION: Children of diabetic pregnancies face increased risks of developing HL, particularly bilateral and sensorineural hearing loss. Given these findings, we recommend close audiologic follow-up for these children, especially those with complicated birth histories or additional medical problems.

Early neonatal hypoglycemia: incidence of and risk factors. A cohort study using universal point of care screening.

OBJECTIVE: The objective of this study is to determine the true incidence of early neonatal hypoglycemia and to confirm potential risk factors. STUDY DESIGN: The study was conducted at tertiary Medical Center in Israel, between June and September 2014. First blood glucose concentrations of all infants admitted to the nursery were measured using a "point of care" analyzer (Accu-Chek). We recorded risk factors for hypoglycemia such as birth weight, gestational age, maternal diabetes and demographics and analyzed their association with two hypoglycemia cutoffs: 40 and 47 mg/dl. RESULTS: Of 4000 newborns admitted during that period, 3595 were analyzed after excluding 405 who had missing data. Glucose level was obtained at a mean age of 74 ± 30 min. One hundred and twenty-four newborns (3.4%) had blood glucose levels below 40 mg/dl and 435 (12.1%) below 47 mg/dl. Univariate analyses revealed that gestational age, maternal diabetes, low birth weight (<2500 g), and twin delivery were associated with early neonatal hypoglycemia. Other risk factors (e.g. large or small for gestational age, birth weight >3800 g) were not. In multivariate analysis, gestational age remained the strongest association, while maternal diabetes and low birth weight became non-significant. CONCLUSIONS: We showed a high occurrence of early hypoglycemia in normal newborns using universal screening. The strongest risk factor was early gestational age. Surprisingly, incidence of early hypoglycemia in the presence of other classical risk factors was like that of the general population.

Effect of well-controlled gestational diabetes on left ventricular diastolic dysfunction in neonates.

BACKGROUND: There are some evidences supporting the relation between gestational diabetes mellitus (GDM) and diastolic dysfunction. The aim of our study was to investigate the effect of well-controlled GDM on morphological and functional myocardium. MATERIALS AND METHODS: We designed a prospective cross-sectional study to evaluate left ventricular (LV) diastolic function of 60 neonates born from mothers with well-controlled GDM (case group) on days of 3-5 after birth. The infants of diabetic mothers (IDM) group were divided into two groups: diabetic mothers treated only with diet (class A) and group of mothers on medical therapy by insulin or metformin (class B). Traditional echocardiography and pulsed-wave Doppler (PWD), tissue Doppler imaging (TDI) were performed for all the neonates. RESULTS: The study group consisted of 60 neonates as males (M) = 32, (0.53%) and females (F) = 28, (0.46%). Using M-mode echocardiography, interventricular septum thickness (IVS), and LV mass were significantly higher in IDM than control group (p = .0001). The PWD showed both a significantly more peak mitral flow at early diastolic wave (E) and an early filling deceleration time (E-DT) (p = .0001). Tissue Doppler echocardiography parameters A' (cm/s) (p = .0001), E' (cm/s) (p = .002), and E'/A' ratio (p = .0001), left ventricular myocardial performance index (LVMPI), and isovolumetric relaxation time (IVRT) were outstandingly different between the two groups (p = .0001, respectively). Evaluating the GDM group mothers of class A and class B, no significant difference was noted in PWD or TDI parameters compared with the healthy ones. CONCLUSIONS: It seems that neonates of mothers with well-controlled GDM are still at increased risk of cardiac hypertrophy, subclinical diastolic dysfunction, and impaired left ventricular relaxation. This can be interpreted that focusing only on glycemic control is not enough to prevent cardiac dysfunction.

Challenging diagnosis of congenital hyperinsulinism in two infants of diabetic mothers with rare pathogenic KCNJ11 and HNF4A gene variants.

BACKGROUND: Congenital hyperinsulinism (CHI) is the leading cause of persistent hypoglycemia in infants. The infants of diabetic mothers (IDMs) very frequently present with neonatal hypoglycemia associated to transient hyperinsulinism however the incidence of CHI in IDMs is unknown. CASE PRESENTATION: Here we report 2 cases of CHI where the diagnoses were challenged and delayed because both patients were infants of diabetic mothers (IDMs) and had concomitant complicated medical conditions. Case 1 was heterozygous for a likely pathogenic variant in KCNJ11(p.Arg206Cys), and Case 2 was heterozygous for a pathogenic HNF4A variant, (p.Arg267Cys). HNF4A-associated CHI is very rare, and this particular case had a clinical phenotype quite different from that of previously described HNF4A-CHI cases. CONCLUSIONS: This case series is one of few reports in the medical literature describing two IDMs with persistent recurrent hypoglycemia secondary to CHI, and a different clinical phenotype for HNF4A-associated CHI. IDMs typically present with transient hyperinsulinism lasting no more than 2-3 days. Since being an IDM does not exclude CHI, this diagnosis should always be considered as the mostly likely etiology if neonatal hypoglycemia persists longer than the described time frame and genetic testing for CHI confirmation is highly suggested.

Correlation of maternal A1c with glucose infusion rate requirements in the newborn.

OBJECTIVE: Fetal hyperinsulinemia and neonatal hyperglycemia are complications of poor maternal glycemic control and may result in increased glucose infusion rate (GIR) requirements in infants of diabetic mothers (IDMs). The objectives of this study were to correlate maternal A1c levels with GIR requirements in IDMs, establish an A1c threshold predictive for GIR requirements, and identify associations between A1c levels and complications in IDMs. STUDY DESIGN: A retrospective review of paired maternal A1c values and GIR requirements of IDMs were compared via logistic regression analysis. A likelihood ratio was calculated to correlate A1c levels with GIR requirements, and identify a maternal A1c threshold. RESULTS: Increasing A1c values were significantly correlated with GIR≥5 mg/kg/min (OR, 1.37; 95% CI 1.04-1.79, p = 0.021). Macrosomia was the most frequent complication (OR, 1.31; 95% CI 1.04-1.67, p = 0.022) and A1c > 6.8% was predictive for increased GIR requirements. CONCLUSION: Increased A1c values were significantly associated with GIR requirements≥5 mg/kg/min. Increased maternal A1c is significantly associated with complications in newborns, specifically macrosomia. A maternal A1c of 6.8% was identified as a threshold predictive of increased GIR requirements.

Clinical profile and pattern of congenital heart disease in infants of diabetic mother and infants of non-diabetic mother at a tertiary care hospital.

OBJECTIVES: To assess the clinical manifestations and pattern of congenital heart diseases (CHD) in infants of diabetic mothers (IDMs) and infants of non-diabetic mothers. METHODS: A prospective cross sectional study was carried out at tertiary care center over a period of thirty months. All neonates were included in this study if CHD were identified by echocardiography within this study period. Chi-square test and Fisher's exact test were used to compare between groups. RESULT: Out of 62 neonates, IDMs and non-IDMs were equal in number, male and female ratio was 3 : 2, and majority were delivered by cesarean section (85.5%). Mean gestational age was 35 weeks, 62.3% were preterm, and 37.7% were term. Common clinical presentations were cardiac murmur (61%), and respiratory distress (43.5%). Less common presentations were low SaO2 (27.4%), tachycardia (24.2%), and cyanosis (24.2%). Common combination of presentations were murmur and tachypnea (38.7%); cyanosis and low SaO2 (24.19%); and low SaO2 and tachypnea 15(24.19). The common echocardiographic findings were atrial septal defect (ASD; 72.6%), patent ductus arteriosus (PDA; 45.2%), and ventricular septal defect (VSD; 25.8%). ASD (77.4% vs 67.7%) and VSD (35.5% vs 16.1%) were more in IDMs, and PDA (48.4% vs 41.9%) was more in non-IDMs. These differences were not significant between groups. CONCLUSION: Clinical presentation and echocardiographic findings of CHD were similar in IDMs and non-IDMs.