Neonatal hypoglycaemia in infants of diabetic mothers

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.     

Growth hormone release during insulin tolerance test on children of short stature

The HGH response to insulin-induced hypoglycaemia has been studied in 31 children with short stature. Ten patients have been classified as hypopituitary dwarfs, and all these patents showed an HGH increment of less than 10 ng/ml from fasting levels. In six of these there were signs of deficiency of other pituitary hormones and two had a craniopharyngioma. In fifteen children the diagnosis was premordial dwarfism or constitutional delay in growth. Two patients in this group showed a subnormal HGH response to insulin-induced hypoglycaemia. In five patients with Turner's syndrome and in two patients with chondrodystrophy the HGH response was normal when compared to a control group. Other parameters compared were the blood glucose levels during the insulin-induced hypoglycaemia, PBI, excretion of 17-OH corticosteroids after metyrapone, urinary gonadotropins and the bone age. The difficulties in the interpretation of different tests are discussed and some other possible tests for the study of HGH release have been described. On the basis of this study measurements of HGH levels during insulin-induced hypoglycaemia is a useful aid in the diagnosis of hypopituitarism. When borderline results are found further tests or short term therapy with HGH is necessary.     

Neontal hypoglycaemia in infants of insulin-dependent diabetic mothers.

Neonatal hypoglycaemia (blood glucose smaller than 20 mg/100 ml) occurred in the first 6 hours of life in 25 of 34 infants born to diabetic mothers receiving insulin. Despite severe hypoglycaemia (blood glucose smaller than 10 mg/100 ml) in 17, clinical features of hypoglycaemia were absent in all but 2. Hypoglycaemia was not related either to the level of plasma insulin in cord blood, determined as nonextracted immunoreactive insulin, or to the degree of control of maternal blood glucose during pregnancy. The frequent occurrence of severe neonatal hypoglycaemia in the infants born to diabetic mothers receiving insulin appears to be due rather to failure to maintain basal glucose homoeostasis after birth than to hyperinsulinism.     

Serum concentration of gentamicin in newborn infants

Serum levels of gentamicin were determined in 15 premature infants (birth weight 1,120-2,250 g, gestational age 27-36 weeks) by agar immunoassay. The intramuscular applied doses was 6 mg/kg/day, the doses interval 12 hours. We found an increase of the gentamicin serum level during the first 72 hours after the beginning of therapy. At the second day of treatment the serum levels in 46.5% of all patients were determined below the therapeutic concentration, but a toxic level was found in more than 60% of all cases during the period of steady state. The serum levels were higher in preterm newborns of less than 1,500 g birth weight, then in more mature infants. We recommend: 1. To double the first doses of gentamicin 2. To modify the gentamicin level by expanded intervals of therapy and/or reduced doses under monitoring, especially during the first week of life.     

Glucose disappearance in infants of diabetic mothers I. Relationship to maternal glucose tolerance and insulin production

Glucose disappearance and insulin response were determined in mother--infant pairs of normal, gestational diabetic and diabetic pregnancies following an intravenous glucose load. Mothers were studied in the third trimester of pregnancy and at least 6 wk postpartum. Significant differences were present in glucose disappearance and insulin response in both gestational diabetic and diabetic mothers during pregnancy compared with the control group. Infants were studied within 4 h of birth while fasting, and glucose and insulin levels followed through the first 3 days of life. Neonatal hypoglycemia did not occur and glucose disappearance (KT) was not different among the three groups. There was no correlation between maternal glucose tolerance or insulin production and that of their infants. The only distinguishing factor among the infants was higher insulin production in infants of diabetic mothers during the 60-min intravenous glucose tolerance test which persisted up to 4 h following the infusion. It is concluded that factors other than the degree of maternal glucose tolerance are responsible for the development of neonatal hypoglycemia in infants of diabetic mothers, most notably control of maternal diabetes, the amount of glucose infused immediately before delivery and neonatal glucose production.     

CLINICAL ASPECTS OF NEONATAL HYPOGLYCAEMIA

ABSTRACT. Fluge, G. (Department of Paediatrics, University of Bergen, Bergen, Norway). Clinical aspects of neonatal hypoglycaemia. Acta Paediatr Scand, 63: 826, 194.—Fifty cases of neonatal hypoglycaemia were detected by routine blood glucose determination in 323 low birth weight infants during a three-year period (15.4%) and, in addition, hypoglycaemia was diagnosed in 17 full-term infants. The patients were divided in three groups according to clinical findings, with special reference to age at diagnosis, pretreatment blood glucose values and duration of hypoglycaemia. In asymptomatic hypoglycaemia the diagnosis was made during the first few hours after birth, and the mean pretreatment blood glucose value was 14 mg/100 ml. Except for one patient, the hypoglycaemia was of short duration. Symptomatic, transient hypoglycaemia was characterized by a delay in onset of symptoms until the second and third day after birth, low pretreatment blood glucose level and hypoglycaemia of long duration. Hypoglycaemia associated with other neonatal disorders classified as secondary hypoglycaemia usually was noted during the first few hours of life, and tended to he of short duration. Frequency of hypoglycaemia in small for gestational age infants was markedly higher when toxaemia of pregnancy was noted, compared with infants born to non-toxaemic mothers.     

Sympatho-adrenal response to hypoglycaemia in infants

The response of the sympathoadrenal system to hypoglycaemia of different etiology was studied in seven infants, aged 10–189 days. Five infants had hyperinsulinism secondary to nesidioblastosis or to a -cell adenoma of the pancreas, one infant had neonatal sepsis due to staphylococcal infection and one infant congenital growth hormone (HGH) and adrenocorticotropic hormone (ACTH) deficiency. In babies with hyperinsulinism, plasma noradrenaline increased from 0.29±0.03 to 0.61±0.09 ng/ml (P<0.01), whereas adrenaline increased only in three, but did not change in two babies. Increases in heart rate and blood pressure paralleled these changes. In hypoglycaemia due to congenital sepsis, noradrenaline increased from 0.39 to 1.64 ng/ml and adrenaline from 0.05 to 0.86 ng/ml. This was associated with marked haemodynamic changes. In congenital HGH and ACTH deficiency, the low basal plasma levels of noradrenaline (0.12 ng/ml) and adrenaline (0.01 ng/ml) remained unchanged in response to hypoglycaemia. Heart rate and blood pressure were unaffected. The sympathoadrenal system was activated by hypoglycaemia in all infants except in congenital HGH and ACTH deficiency. In contrast to adults, noradrenaline was the preferentially released catecholamine, suggesting an involvement of noradrenaline in glucose counter regulation in infancy.Abbreviations ACTH adrenocorticotropic hormone - HGH human growth hormone     

Measurements of bone turnover markers in premature infants

We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p<0.01). Circulating ICTP levels increased in the first week of life and then decreased gradually throughout the follow-up (p<0.01). The study participants were divided into premature infants born at extremely low birth weight (ELBW: <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were significantly higher in VLBW preterms. These results suggest increased bone formation in premature infants in the first three months of life. The increased bone turnover in VLBW compared to ELBW premature infants may be the result of a generally higher morbidity in ELBW preterm infants in early stages of life.     

Interleukin-1 balance in the lungs of preterm infants who develop bronchopulmonary dysplasia

BACKGROUND: The local pulmonary balance between the agonist and antagonist of interleukin-1 (IL-1) may influence the development of inflammatory disease and resultant structural damage in a variety of human diseases including adult respiratory distress syndrome and asthma. OBJECTIVES: We tested the hypothesis that IL-1 cytokines are early markers for bronchopulmonary dysplasia (BPD), when measured in tracheal aspirates (TAs) obtained from premature infants being ventilated for respiratory distress syndrome during the first week of life. METHODS: Serial TAs were collected on days 1, 3, 5 and 7 from 35 preterm infants (16 BPD, 19 non-BPD) in the absence of chorioamnionitis, and were assayed for IL-1 cytokines and leukocytes. RESULTS: In spite of comparable maternal demographic and clinical characteristics, premature infants who developed BPD had higher levels of IL-1 receptor antagonist (Ra) in their airways on the first day of life. This antagonist IL-1Ra was an early and persistent marker for BPD during the first week of life. The agonist IL-1beta also increased significantly for BPD patients early, both compared to non-BPD patients, and also within the BPD group. While the early (day 1) IL-1 antagonist/agonist molar balance offered protection, by days 5 and 7, a threshold for IL-1Ra in the presence of increasing IL-1beta expression-favored pro-inflammation in the BPD group. CONCLUSIONS: We conclude that a strong and early expression of airway antagonist (IL-1Ra) proves ultimately to be sub-optimal and non-protective due to the robust expression of airway agonist (IL-1beta) seen by day 5 in premature infants who develop BPD.     

Cardiac troponin I levels and its relation to echocardiographic findings in infants of diabetic mothers

ABSTRACT: BACKGROUND: Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms responsible for it are unknown. The aim of this study was to compare between infants of diabetic mothers (IDM) and infants of non- diabetic mothers (INDM) as regards cardiac troponin I (cTnI) levels (as a marker of cardiac dysfunction) and to examine the relationship between this marker and neonatal echocardiographic changes (cardiac structure and function). METHODS: A prospective, comparative study included eighty full term neonates during the first three days of life, during the period from April 2008 to June 2011. They were divided into 2 groups, group I: included 40 infants of diabetic mothers (IDMs)and group II: included 40 infants of non diabetic healthy mothers as a control group. RESULTS: 37.5% of the IDMs were large for gestational age and demonstrated a significantly lower blood glucose level than the control group (34.6 +/- 11.3mg/dl Vs 77.2 +/- 19.8 mg/dl respectively) , respiratory distress and cyanosis were the presenting signs in 67.5% of IDMs. Cardiac TnI on the second day of life increased significantly in infants of diabetic mothers in comparison to INDM (p < 0.006) . IDMs had a significant increase in left atrial thickness ( 11.5 +/- 1.8mm in IDM Vs 10.5 +/- 0.9mm in INDM P < 0.002*) and a significant increase in septal thickness (5.0 +/- 1.2mm in IDM Vs 4.0 +/- 0.5mm in INDM P < 0.001*). CTnI correlated positively with interventricular septum thickness (P-value = 0.002*). Cardiac TnI was significantly increased in IDMs with respiratory distress (P -value < 0.05). CONCLUSIONS: This study demonstrated a highly significant positive correlation between cTnI level on the second day of life and the left ventricular end diastolic diameter (LVED) and interventricular septum diameter (IVSD). Cardiac troponin I (cTnI) is a useful biochemical marker for monitoring myocardial injury in infants of diabetic mothers. An elevated cTnI concentration in infants of diabetic mothers with respiratory distress was a good predictor for hypertrophic cardiomyopathy and/or left ventricular dysfunction.     

Thrombocytosis and increased circulating platelet aggregates in newborn infants of polydrug users.

Thirty-three prospectively studied neonates born to mothers using methadone plus other drugs developed significant thrombocytosis by the second week of life compared to platelet counts performed during the first week. This increase persisted for over 16 weeks, with a further short-lived significant peak at 10 weeks of age. Platelet counts exceeding 1,000,000/mm3 were found in seven infants. Thrombocytosis was not related to withdrawal symptoms or treatment (phenobarbital or paregoric). No thrombocytosis was found in 36 normal control infants up to eight weeks of life. Twenty-eight of the study group infants were evaluated for circulating platelet aggregates. Thirteen patients had a normal aggregate index and a mean platelet count of 468,000/mm3; 15 patients had increased aggregates and mean platelet count of 754,000/mm3. The risk for increased circulating platelet aggregates correlated directly with an increase in platelet count. Thrombocytosis and increased circulating platelet aggregates may be factors in the pathogenesis of the focal infarcts, and subarachnoid and germinal plate hemorrhages, described at autopsy in infants of addicted mothers.     

Macro-mineral content of milk obtained during early lactation from mothers of premature infants

Milk from mothers giving birth prematurely was analyzed for Na, C1, K, Mg, Ca and P concentrations. The data presented are from analyses of milk samples representative of complete 24-hour expressions and collected serially over the first 29 days of lactation from mothers giving birth at term (FT) and mothers giving birth prematurely (PT).Mineral composition of FT and PT milks was similar during the first month of lactation. With the exceptions of Mg and P, the concentrations of the minerals studied were higher initially than at the end of the fourth week of lactation. From these data, intakes of premature infants fed their own mothers' milk can be estimated and compared to predicted mineral requirements for the premature infant. On the basis of this comparison, we suggest that the quantities provided of Na, C1, K and Mg, but not Ca and P, would be adequate to meet requirements of premature infants during the early weeks of life.     

Neonatal parathyroid secretion and renal receptor maturation in premature infants.

16 premature infants with normal trophicity were studied during the 1st week of life using serum parathormone (IPTH) dosage and evaluation of renal tubule maturation by the effect of exogenous parathormone (PTE) on urinary elimination of 3':5'-cyclic adenosine monophosphate (cAMP). As of the 1st day, IPTH levels reached or surpassed those in the adult. Prematurity thus does not appear to influence parathormone response. Given the specificity of the dosage antiserum, it appears reasonable that the PTH detected is biologically active. After PTE, urinary elimination of cAMP does not appreciably increase until the 6th day, while still remaining much lower than adult levels. The lower the weight of the premature infant, the less intense the response of the kidney. It thus seems possible that the later development of renal parathormone receptor in the premature infant may be a factor responsible for neonatal hypocalcemia with hyperphosphatemia.     

Impaired vascular reactivity in newborn infants of smoking mothers

A transcutaneous PO2 technique was used to study the influence of cigarette smoking during pregnancy on postocclusive reactive hyperaemia of the skin of newborn infants and their mothers. Forty-seven mothers and their infants were studied on two occasions (24-48 and 96-144 h) after birth. Twenty of the mothers were habitual smokers, 27 were non-smokers. All mothers were healthy and their pregnancies and deliveries were normal. The infants were all healthy throughout their first week of life. The mothers had more marked reactive hyperaemia than their newborn infants (p less than 0.001). Infants of smoking mothers had a significantly weaker postischaemic hyperaemic response 24-48 h after birth than infants of nonsmoking mothers (p less than 0.01). This difference had disappeared 96-144 h after birth. Smoking mothers also showed a significantly weaker hyperaemic response to ischaemia than the control mothers at the first investigation (p less than 0.05). This difference was smaller and not statistically significant at the second recording. A decreased capacity for postocclusive reactive hyperaemia might be particularly harmful in asphyctic infants, but it may also be detrimental for a normal postnatal circulatory adaptation.     

Urinary cyclic AMP in infants admitted to a neonatal intensive care unit.

The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly selected infants admitted to a neonatal intensive care unit. The data were compared with those of normal newborn infants. Urinary cyclic AMP concentrations were significantly correlated with gestational age (all patients), and with birth weight (all patients except infants of diabetic mothers (IDMs)). The urinary cyclic AMP/creatine ratio increased from day 1 to day 3 in normal newborns and in IDMs, and tended to increase also in small-for-gestational age (SGA), low birth weight (LBW), and sick, term infants, although the changes in the latter groups were not statistically significant. Four infants studied with parallel determinations showed increased cyclic AMP/creatinine ratio from day 1 to day 3 both in plasma and urine. All urinary cyclic AMP/creatine ratios were lower than the corresponding ratios found in plasma. In LBW infants, there was an inverse relationship between urinary cyclic AMP and serum calcium. In IDMs a positive correlation was observed between urinary cyclic AMP and blood glucose concentration. In conclusion, the excretion of cyclic AMP in sick newborn infants is influenced by the following factors: gestational age, postnatal age, birth weight, and derangements of serum calcium and blood glucose concentrations.     

Cardiorespiratory depression and plasma beta-endorphin levels in low-birth-weight infants during the first day of life

Twenty-nine premature infants were studied to determine whether neonatal asphyxia, apnea, and low blood pressure in the first day of life are associated with elevated plasma beta-endorphin concentrations. Plasma beta-endorphin levels were determined at 0.5 to 2, 4 to 6, and 18 to 24 hours of life, using radioimmunoassay. Premature infants with moderate or severe asphyxia (n = 19) had higher levels at 0.5 to 2 hours of age (32.1 +/- 6.7 vs 16.4 +/- 7.4 pmol/L) and significantly higher levels at 4 to 6 hours of age (50.4 +/- 10.0 vs 22.9 +/- 9.2 pmol/L) compared with the ten nonasphyxiated premature infants. A significant elevation in levels at age 0.5 to 2 hours (39.4 +/- 9.9 vs 17.7 +/- 4.4 pmol/L) and age 4 to 6 hours (59.3 +/- 13.8 vs 27.1 +/- 17.1 pmol/L) was observed in premature infants with low blood pressure or impaired perfusion (n = 12) who required the administration of volume expanders. No differences were observed in premature infants with and without apnea. It may be speculated that the increased endogenous release of beta-endorphins in response to perinatal asphyxia may play a role in the pathogenesis of shock observed in the first day of life.     

Parathormone and perinatal calcium homeostasis.

Plasma parathormone (PTH) and calcium concentrations were measured in 309 specimens collected from 190 newborns during the first 7 days of life. The patient material consisted of 51 preterm, 130 term, and 9 postterm infants, including 22 infants of diabetic mothers (IDM), 38 infants with hypocalcemia, and 25 asphyxiated infants. PTH was detectable, although in low concentrations, in cord blood samples despite the presence of elevated calcium concentrations. Postpartum, PTH concentrations in term, appropriate for gestational age (AGA) infants remained low during the first 2 days of life; a significant (P less than 0.05) and sustained increase in plasma hormone levels was noted starting on day 3. PTH concentrations in IDM and preterm infants remained low for 3 days and a significant hormone increase did not occur until day 4. Hypocalcemia was common in IDM and asphyxiated infants; these infants accounted for two-thirds of all hypocalcemic infants. The profile of plasma calcium in IDM during the first week of life was different than that of any other group of infants. Plasma calcium concentrations remained depressed over this period of time and exhibited a temporary drop on day 4 accompanied by an increase in plasma PTH levels. Asphyxiated infants exhibited low plasma calcium concentrations, despite PTH levels that were significantly (P less than 0.007) higher than those of age-matched term AGA newborns.     

Growth hormone levels in children during long-term treatment with corticosteroids

The growth hormone increment induced by hypoglycaemia has been studied in 17 children treated with corticosteroids. No difference in fasting levels was found between normal children and Cortisone-treated children. An inhibition in HGH release due to insulin-induced hypoglycaemia was found as well as a correlation between the inhibition of HGH release and dosage of corticosteroids. Furthermore a correlation between mean dose of corticosteroids per year and height increment was observed. The bone age was delayed in nine of the children all of them having high doses of steroids. The mode of the inhibition to HGH release is discussed. Reduced growth is most likely due as well to factors other than inhibition of HGH release. Despite the disadvantage in method of administration, ACTH might be tried more frequently.     

Plasma carnitine and breast milk carnitine intake in premature infants

Ten premature infants with a mean gestational age of 29 weeks (range, 27-32) and a mean birth weight of 1,294 g (range, 930-2,300) and without complications at birth were studied during the first 14 days after birth. Their breast milk intake was recorded and the carnitine content determined in each daily portion. During the first week, the daily mean carnitine intake was low and increased to 6-7 mumoles/kg and day during the second week. Breast milk carnitine concentration ranged from 17 to 148 mumoles/L. Plasma carnitine and its derivatives did not change during the observation period. No relationship was found between the individual cumulative breast milk carnitine intake and total plasma carnitine levels or between carnitine and its derivatives and nonesterified fatty acids or 3-OH-butyrate. The urinary carnitine excretion, in millimoles of carnitine per mole of creatinine, was higher during the second week. In other studies, declining plasma carnitine levels have been observed in premature infants on total parenteral nutrition. The results from this study indicated that premature infants without complicating disorders were able to maintain their plasma carnitine levels.     

Serum concentrations of thyrotropin, thyroid hormones and thyroid hormone-binding proteins during acute and recovery stages of idiopathic respiratory distress syndrome.

A total number of 27 premature infants with idiopathic respiratory distress syndrome (IRDS) and 52 healthy controls with comparable gestational age and body weights were studied during the first month of life. In infants with IRDS a reduced thyrotropin (TSH) response to birth was suggested, as serum TSH was lower in IRDS patients than in controls during the first two days of life. Low serum concentrations of thyroid hormones were found in the acute stage of IRDS reaching minimal values by day 3--5. After that period an increase in thyroid hormone levels occurred. The serum T2 increased to the level of healthy prematures by day 6--10, whereas the serum T4 increased to normal levels by day 21--30. Serum concentrations of thyroxine-binding globulin (TBG) were significantly lower in IRDS patients than in healthy controls; a gradual increase to normal levels occurred during recovery. Serum prealbumin (TBPA) levels in IRDS infants increased rapidly after birth and exceeded levels of healthy infants. Serum albumin values were not significantly different in the two groups of infants. The serum T4/TBG ratios were low during recovery from IRDS.