Associations of ultrasound estimated early mid pregnancy visceral and subcutaneous fat depths and early pregnancy BMI with adverse neonatal outcomes.

This study investigated whether maternal central adiposity and body mass index (BMI) were associated with neonatal hypoglycemia and adverse neonatal outcomes. A cohort study was performed at Uppsala University Hospital, Sweden, between 2015 and 2018. Visceral and subcutaneous fat depths were measured by ultrasound at the early second-trimester anomaly scan in 2771 women giving birth to singleton infants. Body mass index was assessed in early pregnancy. Logistic regression models were performed. Adjustments were made for age, BMI (not in model with BMI as exposure), smoking, maternal country of birth, and parity. Outcomes were neonatal hypoglycemia (blood glucose concentration < 2.6 mmol/l), a composite of adverse neonatal outcomes (Apgar < 7 at 5 min of age, or umbilical artery pH ≤ 7.0, or admission to neonatal intensive care unit), and the components of the composite outcome. Visceral and subcutaneous fat depths measured by ultrasound in early mid pregnancy were not associated with any of the outcomes in adjusted analyses. For every unit increase in BMI, the likelihood of neonatal hypoglycemia increased by 5% (aOR 1.05, 95% CI 1.01-1.10), the composite outcome by 5% (aOR 1.05, 95% CI 1.01-1.08), and admission to neonatal intensive care unit by 6% (aOR 1.06, 95% CI 1.02-1.10).

Antenatal betamethasone and the risk of neonatal hypoglycemia: it's all about timing.

INTRODUCTION: Our objective was to evaluate whether there is a relationship between the "time during the day" of maternal betamethasone administration between 24 and 34 weeks' gestation and the risk for neonatal hypoglycemia. MATERIAL AND METHODS: A retrospective study included cases between 2008 and 2018. Eligible cases were pregnant women with singleton pregnancies who received a single course of betamethasone between 24 and 34 weeks' gestation. Each woman was allocated into one of four pre-defined groups based on the time when intramuscular betamethasone was administered. Group 1 (23:00-04:59) represents the lowest daily natural corticosteroids' activity, group 2 (05:00-10:59) represents the peak daily natural corticosteroids' activity, whereas group 3 (11:00-16:59) and group 4 (17:00-22:59) present an intermediate natural state of steady corticosteroids' secretion and activity. The primary outcome of the study was the incidence of neonatal hypoglycemia (glucose level of less than 40 mg/dL). RESULTS: We have identified 868 women who received a single complete course of betamethasone, of which 353 women (40.7%) had a steroid treatment latency to delivery up to 14 days. The incidence of neonatal hypoglycemia was significantly higher in group 2 (39.5%, 30/76, p = 0.0063), compared to group 1, who had the lowest incidence of neonatal hypoglycemia (16.9%, 12/71), and to group 3 and group 4. CONCLUSIONS: The "time during the day" when betamethasone administered is important when considering the risk for neonatal hypoglycemia. The risk was significantly higher when betamethasone was administered during the peak time and significantly lower when administered at the nadir time of maternal endogenous corticosteroid activity.

Complications of Antenatal Corticosteroids in Infants Born by Early Term Scheduled Cesarean Section.

OBJECTIVE: To compare neonatal hypoglycemia and respiratory morbidity rates in pregnancies complicated by diabetes following early term scheduled cesarean section (ETSCS) with and without maternal corticosteroid administration. RESEARCH DESIGN AND METHODS: In a retrospective cohort study, women with any form of diabetes in pregnancy undergoing ETSCS were included. Primary outcomes were admission rates to the neonatal intensive care unit (NICU) for respiratory distress syndrome (RDS)/transient tachypnea of the newborn (TTN) and/or neonatal hypoglycemia. RESULTS: NICU admission rates for neonatal hypoglycemia were significantly higher (24.2% vs. 4.4%, P = 0.003) and RDS/TTN rates were nonsignificantly higher (15.2% vs. 7.2%, P = 0.209) following corticosteroid administration. CONCLUSIONS: Corticosteroids were not beneficial among women with any form of diabetes in pregnancy undergoing ETSCS and, indeed, may be harmful. In our hospital, we have ceased the use of corticosteroids for women under these circumstances.

The association between novel glucose indices in parturients with type 1 diabetes mellitus and clinically significant neonatal hypoglycemia.

The aim of this study was to determine the association between glucose control indices of parturient with type 1 diabetes (T1DM), treated with an insulin pump and utilizing continuous glucose monitoring (CGM), and clinically significant neonatal hypoglycemia. This was a retrospective cohort study which included 37 pregnant women with T1DM. All women were followed at a single tertiary center and had available CGM data. The association between maternal glucose indices before delivery and the risk for neonatal hypoglycemia requiring IV glucose (clinically significant hypoglycemia) was assessed using logistic regression. Mothers to neonates that experienced clinically significant hypoglycemia had a higher glucose standard deviation (SD) before delivery than did mothers to neonates who did not (25.5 ± 13 mg/dL vs. 14.7 ± 6.7 mg/dl respectively; p = .008). This association persisted after adjustment for maternal age, maternal pregestational body mass index (BMI), gestational age at delivery, neonatal birth weight, large for gestational age (LGA) and gender. This study demonstrates an association between high maternal glucose standard deviation before delivery and the risk for clinically significant neonatal hypoglycemia. Larger studies are needed to confirm these results and further explore the role of intrapartum glucose variability in the prediction and prevention of significant neonatal hypoglycemia.

Maternal obesity and degree of glucose intolerance on neonatal hypoglycaemia and birth weight: a retrospective observational cohort study in women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is an increasing problem worldwide. Postnatal hypoglycaemia and excess foetal growth are known important metabolic complications of neonates born to women with diabetes. This retrospective cohort study aims to determine the influence of obesity and glucose intolerance on neonatal hypoglycaemia and birth weight over the 90th percentile (LGA). Data were abstracted from 303 patient medical records from singleton pregnancies diagnosed with GDM. Data were recorded during routine hospital visits. Demographic data were acquired by facilitated questionnaires and anthropometrics measured at the first antenatal appointment. Blood biochemical indices were recorded. Plasma glucose area under the curve (PG-AUC) was calculated from OGTT results as an index of glucose intolerance. OGTT results of 303 pregnant women aged between 33.6 years (29.8-37.7) diagnosed with GDM were described. Neonates of mothers with a BMI of over 30 kg/m2 were more likely to experience neonatal hypoglycaemia (24 (9.2%) vs. 23 (8.8%), p = 0.016) with odds ratio for neonatal hypoglycaemia significantly higher at 2.105, 95% CI (1.108, 4.00), p = 0.023. ROC analysis showed poor strength of association (0.587 (95% CI, .487 to .687). Neonatal LGA was neither associated with or predicted by PG-AUC nor obesity; however, multiparous women were 2.8 (95% CI (1.14, 6.78), p = 0.024) times more likely to have a baby born LGA.Conclusion: Maternal obesity but not degree of glucose intolerance increased occurrence of neonatal hypoglycaemia. Multiparous women had greater risk of neonates born LGA.What is Known:•Excess foetal growth in utero has long-term metabolic implications which track into adulthood.•Neonatal hypoglycaemia is detrimental to newborns in the acute phase with potential long-term implications on the central nervous system.What is New:•Maternal obesity but not degree of glucose intolerance in a GDM cohort increased occurrence of neonatal hypoglycaemia.•Multiparous women diagnosed had greater risk of neonates born LGA.

Risk factors and outcomes for neonatal hypoglycaemia and neonatal hyperbilirubinaemia in pregnancies complicated by gestational diabetes mellitus: a single centre retrospective 3-year review.

AIM: To determine risk factors associated with neonatal hypoglycaemia and hyperbilirubinaemia, and assess their impact on neonatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). METHODS: Retrospective review investigating all pregnancies complicated by GDM at Campbelltown Hospital (Sydney, Australia) between 1 January 2013 and 31 December 2015. Main outcomes measured were neonatal hypoglycaemia (capillary glucose levels < 1.8 mmol/l) and hyperbilirubinaemia (total serum bilirubin levels greater than age-appropriate thresholds for phototherapy). Adjusted odds ratios [95% confidence interval (CI)] are shown, calculated by multivariable logistic regression. RESULTS: Some 60 (7.8%) infants developed hypoglycaemia, 58 (7.5%) developed hyperbilirubinaemia and 13 (1.7%) developed both. Risk of developing hypoglycaemia increased 1.8-fold (95% CI 1.3-2.6, P < 0.001) per gestational week at GDM diagnosis, 1.1-fold (95% CI 1.0-1.3, P = 0.04) per mmol/l maternal fasting glucose, 6.2-fold (95% CI 2.6-16.2, P < 0.001) with maternal history of macrosomia, 10.8-fold (95% CI 4.1-27.6, P < 0.001) with multiple pregnancy and 1.1-fold (95% CI 1.0-1.3, P = 0.04) per gestational week at birth. Risk of hyperbilirubinaemia increased with multiple pregnancy (26.4; 95% CI 11.7-59.7, P < 0.001), and 1.5-fold (95% CI 1.1-2.1, P = 0.01) per gestational week at GDM diagnosis. Hypoglycaemia was associated with a 2.8-fold (95% CI 1.1-7.1, P = 0.03) increased risk of macrosomia, a 5.4-fold (95% CI 1.1-27.3, P = 0.04) excess risk of shoulder dystocia and a 6.4-fold increased risk of 5-min APGAR ≤ 7 (95% CI 1.2-1.7, P < 0.001). Hyperbilirubinaemia was associated with an excess risk of polycythaemia (packed cell volume > 0.6; 97.1, 95% CI 38.9-241.5, P < 0.001). CONCLUSIONS: Neonatal hypoglycaemia and hyperbilirubinaemia largely occur in different pregnancies. Both are associated with earlier GDM diagnosis; however, hypoglycaemia is more associated with maternal glycaemia and its sequelae, and hyperbilirubinaemia is associated with polycythaemia.

In-hospital formula supplementation and breastfeeding initiation in infants born to women with pregestational diabetes mellitus.

OBJECTIVE: To ascertain the rate of in-hospital supplementation as it relates to early breastfeeding (BF) and early formula feeding (FF) and its effects on BF (exclusive and partial) at the time of discharge for infants born to women with pregestational diabetes mellitus (PGDM). METHODS: Retrospective cohort investigation of 282 women with PGDM who intended to BF and their asymptomatic infants admitted to the newborn nursery for blood glucose monitoring and routine care. Early feeding was defined by the initial feeding if given within four hours of birth. RESULTS: Of the 282 mother-infant dyads, for 134 (48%) early feeding was BF and for 148 (52%) early feeding was FF. Times from birth to BF and FF (median 1 hr, 0.3-6) were similar, while the time to first BF for those who FF and supplemented was longer (median 6 hr., 1-24). Ninety-seven infants (72%) who first BF also supplemented. Of these, 22 (23%) BF exclusively, 67 (69%) BF partially and 8 (8%) FF at discharge. One hundred seventeen (79%) who first FF also supplemented. Of these, 21 (18%) BF exclusively, 76 (65%) BF partially and 20 (17%) FF at discharge. CONCLUSION: Regardless of the type of first feeding, the majority of infants born to women with PGDM require supplementation. Even when medically indicated, in-hospital supplementation is an obstacle, albeit not absolute, to exclusive BF at discharge. Parents should be reminded that occasional supplementation should not deter resumption and continuation of BF.

Follow-up study of neurodevelopment in 2-year-old infants who had suffered from neonatal hypoglycemia.

BACKGROUND: Neonatal hypoglycemia is tightly related to adverse neurodevelopmental and brain injury outcomes. METHODS: A total of 195 infants who were born from diabetic mothers with a low blood glucose level (< 2.6 mM) within 0.5 h after birth were enrolled in this prospective cohort study. Of these, 157 infants who had neonatal hypoglycemia (group A) were followed up, and this group was further divided into A1 [blood glucose concentration (BGC) < 2.6 mM at < 2 h after birth], A2 (BGC < 2.6 mM at 2-24 h after birth), and A3 (BGC < 2.6 mM at > 24 h after birth). A total of 144 infants whose mothers had no high risk for gestational diabetes mellitus were followed up as the control group during the same period. The neurodevelopment of the infants was evaluated by the Gesell scoring method. RESULTS: The adaptability in the A2 and A3 subgroups was significantly lower than that in the control group (73.9 ± 6.6 vs. 87.9 ± 11.2; 71.5 ± 8.9 vs. 87.9 ± 11.2, respectively). There were significantly more mothers who used insulin during the perinatal period in A3 than in A1 and A2 (31% vs. 2%; 31% vs. 7.9%, respectively). The mothers of babies in subgroups A2 and A3 gained more weight than those of the control group (15.3 ± 1.9 kg vs. 11.1 ± 2.2 kg; 14.8 ± 2.6 kg vs. 11.1 ± 2.2 kg, respectively). CONCLUSIONS: Long and repeated neonatal hypoglycemia caused poor adaptability. The babies of mothers who used insulin or had a high weight gain during pregnancy were associated with severe or persistent neonatal hypoglycemia.

A rare cause of neonatal hypoglycemia in two siblings: TBX19 gene mutation.

Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rarely seen disease characterized by low serum ACTH and cortisol levels accompanied by normal levels of the other anterior pituitary hormones. In these patients, severe hypoglycemia, convulsions, and prolonged cholestatic jaundice are expected findings in the neonatal period. In this paper, we present two siblings with TBX19 gene mutation. The first case was investigated at the age of 2 months for severe hypoglycemia, recurrent convulsions, and prolonged cholestatic jaundice persisting since the neonatal period. The second sibling presented with hypoglycemia in the neonatal period. In both cases, baseline cortisol and ACTH levels were low and cortisol response to the low-dose ACTH test was inadequate, while all other anterior pituitary hormones were normal. Thus, IAD was suspected. Genetic analysis of the TBX19 gene was performed. Both cases were homozygous for c.856 C>T (p.R286*), and hydrocortisone treatment was initiated. The first patient did not attend the clinic regularly. On attendance at another hospital, hydrocortisone treatment was discontinued and antiepileptic treatment was initiated because of suspected epilepsy. This led to developmental delay, measured with the Denver Developmental Screening Test II (DDST-II), because of cessation of the hydrocortisone therapy. The second sibling had normal development, as measured with the DDST. In conclusion, TBX19 gene analysis must be performed if adrenal insufficiency is associated with isolated ACTH deficiency. Delay in diagnosis may lead to inappropriate diagnoses, such as epilepsy, and thus inappropriate therapy, which may result in neonatal mortality.

Neonatal Hypoglycemia Following Diet-Controlled and Insulin-Treated Gestational Diabetes Mellitus.

OBJECTIVE: To assess the risk of neonatal hypoglycemia following diet-controlled and insulin-treated gestational diabetes mellitus (GDM) and how it relates to birth weight. RESEARCH DESIGN AND METHODS: Prospective cohort study included term neonates born after GDM from January 2013 through December 2015 at the University Medical Center Utrecht (Utrecht, the Netherlands). Routine screening of neonatal blood glucose levels was performed at 1, 3, 6, 12, and 24 h after birth. Main outcome measures were neonatal hypoglycemia defined as blood glucose ≤36 mg/dL (severe) and ≤47 mg/dL (mild). RESULTS: A total of 506 neonates were included, born after pregnancies complicated by GDM treated either with insulin (22.5%) or without insulin (77.5%). The incidence of mild and severe hypoglycemia was similar in the insulin-treated and diet-controlled groups (33 vs. 35%, P = 0.66; and 20 vs. 21%, P = 0.79). A birth weight >90th centile was seen in 17.2% of all infants. Although children with a birth weight >90th centile had the highest risk for hypoglycemia, the vast majority of hypoglycemia (78.6%) was detected in those with a birth weight <90th centile. Over 95% of all hypoglycemia occurred within 12 h after birth. CONCLUSIONS: Routine screening for neonatal hypoglycemia following pregnancies complicated by GDM reveals high incidence of both mild and severe hypoglycemia for both diet-controlled and insulin-treated GDM and across the full range of birth weight centiles. We propose routine blood glucose screening for neonatal hypoglycemia within the first 12 h of life in all neonates after GDM, irrespective of maternal insulin use or birth weight.

Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome.

Recently, the genetic cause of several syndromic forms of glycemia dysregulation has been described. One of them, MEHMO syndrome, is a rare X-linked syndrome recently linked to the EIF2S3 gene mutations. MEHMO is characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. Moreover, patients with MEHMO had also diabetes and endocrine phenotype, but detailed information is missing. We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. Both probands had a neonatal hypoglycemia, early onset insulin-dependent diabetes, and hypopituitarism due to dysregulation and gradual decline of peptide hormone secretion. Based on the clinical course in our two probands and also in previously published patients, neonatal hypoglycemia followed by early-onset diabetes and hypopituitarism may be a consistent part of the MEHMO phenotype.

The duration of intrapartum maternal hyperglycaemia predicts neonatal hypoglycaemia in women with pre-existing diabetes.

AIM: There is a high incidence of neonatal hypoglycaemia in neonates born to mothers with pre-existing diabetes. This often necessitates admission to the neonatal intensive care. Guidelines suggest maintaining intrapartum blood glucose levels (BGLs) of 4-7 mmol/l in women with diabetes to reduce the risk of neonatal hypoglycaemia. This study assessed whether intrapartum BGLs in women with pre-gestational Type 1 and 2 diabetes were predictive of neonatal hypoglycaemia. METHODS: A retrospective analysis of 261 births delivered at a tertiary hospital in Australia from 2009 to 2014. RESULTS: There were 122 cases of neonatal hypoglycaemia (glucose ≤ 2.6 mmol/l) in 261 births (47%). The mothers in the neonatal hypoglycaemia group spent less time with BGL in the range 4-7 mmol/l [55 ± 37% vs. 65 ± 35%, P = 0.02; odds ratio (OR) 0.992, P = 0.03] and more time with BGL in the 7-10 mmol/l range (31 ± 34% vs. 18 ± 27%, P = 0.003; OR 1.013, P = 0.003) compared with those without neonatal hypoglycaemia. Although statistically significant, receiver operating characteristic (ROC) curve analysis showed that time spent with maternal BGLs in the range 4-7 mmol/l [area under the curve (AUC) = 0.58] or 7-10 mmol (AUC = 0.60) was not strong enough to be a useful clinical predictor of neonatal hypoglycaemia. HbA1c in the second trimester of pregnancy (P = 0.02, OR 1.42) and percentage time spent in BGL range of 7-10 mmol/l (P = 0.001, OR 1.02) were both associated with a risk of neonatal hypoglycaemia in a logistic regression model. HbA1c in the third trimester (P = 0.07, OR 1.28) approached, but did not reach, significance. CONCLUSIONS: These data support a BGL range of 4-7 mmol/l as an intrapartum target. Glycaemic control in the second trimester is associated with neonatal hypoglycaemia. Improvement in ante- and intrapartum glycaemic control may reduce neonatal hypoglycaemia in women with pre-existing diabetes.

Neonatal hypoglycemia.

A consistent definition for neonatal hypoglycemia in the first 48 h of life continues to elude us. Enhanced understanding of metabolic disturbances and genetic disorders that underlie alterations in postnatal glucose homeostasis has added useful information to understanding transitional hypoglycemia. This growth in knowledge still has not led to what we need to know: "How low is too low and for how long?" This article reviews the current state of understanding of neonatal hypoglycemia and how different approaches reach different "expert" opinions.

Congenital Hypoglycemia Disorders: New Aspects of Etiology, Diagnosis, Treatment and Outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016.

Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism (HI) is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of HI have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular, and imaging findings to establish the appropriate treatment according to the subtype. Here we present a summary of a recent international symposium on congenital hypoglycemia disorders with emphasis on novel molecular mechanisms resulting in HI, genetic diagnosis, overall approach to management, novel therapies under development, and current outcomes.

A novel mutation in the glutamate dehydrogenase (GLUD1) of a patient with congenital hyperinsulinism-hyperammonemia (HI/HA).

Hyperinsulinism-hyperammonemia (HI/HA) syndrome, often characterized by recurrent symptomatic hypoglycemia and persistent hyperammonemia, is the second most frequent cause of the congenital hyperinsulinism (CHI). Here, we reported a patient with normal birth weight, repeated seizures, untreatable hypoglycemia, and persistent, mild hyperammonemia. The genetic diagnosis revealed that the patient carried a heterozygous, de novo missense mutation (N410I, c.1401A>T) in the glutamate dehydrogenase 1 gene (GLUD1). The patient was treated with diazoxide, which significantly alleviated the hypoglycemia. CT and MRI brain scanning at different developmental stages revealed large-scale brain damage in the front lobe. Severe neurodevelopment deficits were identified in the follow-up.

Treatment With Diet and Exercise for Women With Gestational Diabetes Mellitus Diagnosed Using IADPSG Criteria.

CONTEXT: Prevalence of gestational diabetes mellitus (GDM) and obesity continue to increase. OBJECTIVE: This study aimed to ascertain whether diet and exercise is a successful intervention for women with GDM and whether a subset of these women have comparable outcomes to those with normal glucose tolerance (NGT). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of five antenatal centers along the Irish Atlantic seaboard of 567 women diagnosed with GDM and 2499 women with NGT during pregnancy. INTERVENTION: Diet and exercise therapy on diagnosis of GDM were prescribed and multiple maternal and neonatal outcomes were examined. RESULTS: Infants of women with GDM were more likely to be hypoglycemic (adjusted odds ratio [aOR], 7.25; 95% confidence interval [CI], 2.94-17.9) at birth. They were more likely to be admitted to the neonatal intensive care unit (aOR, 2.16; 95% CI, 1.60-2.91). Macrosomia and large-for-gestational-age rates were lower in the GDM group (aOR, 0.48; 95% CI, 0.37-0.64 and aOR, 0.61; 95% CI, 0.46-0.82, respectively). There was no increase in small for gestational age among offspring of women with GDM (aOR, 0.81; 95% CI, 0.49-1.34). Women with diet-treated GDM and body mass index (BMI) < 25 kg/m(2) had similar outcomes to those with NGT of the same BMI group. Obesity increased risk for poor pregnancy outcomes regardless of diabetes status. CONCLUSION: Medical nutritional therapy and exercise for women with GDM may be successful in lowering rates of large for gestational age and macrosomia without increasing small-for-gestational-age rates. Women with GDM and a BMI less than 25 kg/m(2) had outcomes similar to those with NGT suggesting that these women could potentially be treated in a less resource intensive setting.