Newborn Infants Of Diabetic Mothers Research Articles

Pain response to vaccination in newborn infants of diabetic mothers

BackgroundResponse to pain is altered in infants who were exposed to pain- and stressful events in the neonatal period. Infants of diabetic mothers receive several heel sticks after birth for measuring blood glucose and thus may show changes in their behavioral and physiologic response to pain. Moreover, maternal hyperglycemia may alter activity of the hypothalamic pituitary adrenal (HPA) axis reactivity. Study designIn total, 43 infants of diabetic mothers and 30 control infants were included into the study. Response to pain was assessed at 3 months of age following two intramuscular injections for vaccination. We assessed behavioral (Bernese pain scale), physiologic (heart rate) and hormonal (salivary cortisol) pain response to vaccination as well as spinal sensitization (flexion withdrawal reflex). ResultsInfants of diabetic mothers received a median number of 5 [4–19] painful events compared to 1 [1–3] in the control group. Heart rate reactivity differed significantly between groups. Infants of diabetic mothers had higher peaks (p = 0.002) and needed more time to recover to baseline (p < 0.001). Moreover, infants of diabetic mothers showed higher peak cortisol (p = 0.001) and a higher relative cortisol increase (p = 0.015). Flexor withdrawal reflex thresholds were significantly lower in infants of diabetic mothers (p = 0.003). ConclusionThe increase of physiologic and hormonal responses to pain in infants of diabetic mothers is probably caused by repeated painful events and an altered metabolic profile.

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 ≥36weeks 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 3.44kg (±0.56), and body surface area (BSA) 0.21m2 (±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.

Abstract 16893: Subclinical Decrease in Myocardial Function in Asymptomatic Infants of Diabetic Mothers: A Tissue Doppler Study

Introduction: Infants of diabetic mothers (IDMs) with cardiac hypertrophy are recognized to have impaired myocardial performance, but less is known about ventricular function in those without hypertrophy. We hypothesized that, in asymptomatic newborns with normal echocardiograms, tissue Doppler imaging (TDI) indices of cardiac function would be decreased in IDMs compared to controls. Methods: This retrospective case-control study involved IDMs ≥ 36 weeks gestational age, at 0 to 7 days of life. Subjects with cardiorespiratory symptoms, ventricular hypertrophy or dysfunction, or any echocardiographic abnormality (other than a patent ductus arteriosus before 4 days of life, or a patent foramen ovale) were excluded. Each subject was matched with 3 controls (healthy infants of non-diabetic mothers) by age (0-24, 25-48, 49-72, or &gt; 72 hours of life), birth weight (± 0.5 kg), body surface area (± 0.03 m 2 ), and by the ultrasound system utilized. TDI systolic (S’), early diastolic (E’), and late diastolic (A’) velocities were measured at the mitral valve (MV) annulus, basal ventricular septum, and tricuspid valve (TV) annulus, and were averaged from 3 consecutive cardiac cycles. Early Doppler inflow velocity to E’ ratios (E/E’) were calculated. Results: Seventy cases (39 male) were identified: first 24 hours (h) of life (n=18), 25-48 h (n=22), 49-72 h (n=14), and &gt; 72 h (n=16). Maternal diabetes was gestational in 60 cases, and pre-existing in 10. Median gestational age was 38 6/7 weeks (range 36-41 2/7), median birth weight 3.65 kg (2.56-5.38), and median BSA 0.22 m 2 (0.17-0.27). Ultrasound system vendors included Siemens ® (n=46), Philips ® (n=23), and General Electric ® (n=1). Cases were matched with 210 controls. IDMs had significantly lower S’ ( p ≤ 0.05) and E’ ( p ≤ 0.01) velocities, and significantly higher E/E’ ratios ( p ≤ 0.01) at the MV, basal septum, and TV compared to controls (Wilcoxon rank-sum test). There were no significant differences in A’ values between groups. Intraclass correlation demonstrated 84-99% interobserver and 98-99% intraobserver reliability. Conclusions: In asymptomatic newborn IDMs without cardiac hypertrophy, TDI suggests a subclinical decrease in systolic and diastolic myocardial function compared to controls.

Video-EEG recordings in full-term neonates of diabetic mothers: observational study

ObjetiveTo determine whether full-term newborn infants of diabetic mothers (IDM) present immature/disorganised EEG patterns in the immediate neonatal period, and whether there was any relationship with maternal glycaemic control.Design and...

Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants

This study determined the effects of cumulative exposure to painful needle procedures and sucrose analgesia on the development of remote hyperalgesia in newborn infants, defined as an increase in response to a normally painful stimulus at a site distal from the site of injury. One-hundred and twenty healthy newborns and 120 healthy newborn infants of diabetic mothers equally randomized to sucrose analgesia or placebo prior to all needle procedures in the first two days after birth were divided into two exposure groups according to number of needle procedures they had undergone [high (⩾5) or low (⩽4)] using the median cut-off technique. Compared to the low exposure group, infants in the high exposure group had a higher pain response during a subsequent venipuncture distal to the site of previous injury, assessed by the Premature Infant Pain Profile (PIPP) [7.1 vs. 8.4; p=0.012] and Visual Analog Scale (VAS) [2.5cm vs. 3.2cm; p=0.047], and a trend for longer cry duration [25.7s vs. 33.8s; p=0.171]. PIPP scores did not differ during a routine diaper change, suggesting a nociceptive specific mechanism for the remote hyperalgesia to venipuncture. Sucrose reduced PIPP, VAS, and cry duration scores during venipuncture, but did not prevent hyperalgesia (p>0.05). There was a preponderance of infants of diabetic mothers in the high exposure group; however, the analysis did not demonstrate this to be a confounding factor. In conclusion, sucrose analgesia for repeated painful procedures in the first day of life does not prevent development of remote hyperalgesia in newborns.

3 Increased Lipolysis in Large for Gestational Age Infants

Background: During late gestation the fetus accumulates fat and glycogen for the immediate postnatal period. Newborn infants of diabetic mothers as well as other infants with hyperinsulinemia have particularly large energy depots and are at risk for hypoglycemia. Large for gestational age (LGA) infants, without known predisposing factors, also have increased energy stores. The relative proportion of this group of infants is increasing. Only limited data is available on the metabolic adaptation of these infants. Aim: To study lipolysis and glucose production in infants born LGA of non diabetic mothers. Methods: Eight term LGA infants, were studied at a postnatal age of 19±8-h. Gestational age was 40±1.5 w and birthweight 4.87±0.44 kg. Rates of lipolysis and glucose production (GPR) were analysed by gas chromatography-mass spectrometry following constant rate infusion of [2–13C]-glycerol and [6,6–2H2]-glucose. Results: Plasma glucose and glycerol averaged 3.8 ± 0.6 mmol. L-1 and 418 ± 190 ±mol. L-1, respectively. Glycerol production, reflecting lipolysis, was 13.2±2.9 imol. kg-1. min-1 and GPR averaged 5.5±0.9 mg. kg-1. min-1 (30.6±5.imol. kg-1. min-1). The fraction of glycerol converted into to glucose was 54±22 % contributing to 11±6 % of the total glucose production. Lipolysis and GPR correlated to birth weight. Plasma concentrations of insulin and glucagon averaged 11±3 mU. L-1 and 39±4 pmol. L-1, respectively. Conclusion: The results show that term LGA infants have a markedly increased lipolysis during the first day of life as compared to term infants born appropriate for gestational age (AGA). The correlation to birth weight indicates that the degree of lipolysis is dependent on the amount of stored fat in the LGA infants. GPR was similar to that observed in AGA infants. There was no pronounced hyperinsulinemia, which contradicts the occurrence of insulin resistance in this particular group of infants.

Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers.

Infants of diabetic mothers (IDMs) are at risk for perinatal brain iron deficiency that may target the developing hippocampus. The objective of this study was to evaluate hippocampally based recognition memory and infant development in IDMs with suspected brain iron deficiency (BID; cord ferritin </=34 microg/L) compared with IDMs with sufficient brain iron stores (BIS; cord ferritin >34 microg/L) using event-related potentials (ERPs). ERPs assessed neonatal auditory cortical responses to sounds and auditory recognition memory in response to the mother's voice compared with a stranger's voice. Thirty-two newborn IDMs had cord serum ferritin concentrations and provided neonatal ERP data (n = 23) and/or blinded 1 y developmental assessments (n = 28). Auditory cortical responses to speech and nonspeech sounds were similar in the BID and BIS groups. In the maternal voice recognition paradigm, peak latencies were shorter in the BID group than in the BIS group. Infants in the BIS group displayed a significant negative slow wave for the strangers' voices compared with the mothers' voices, whereas the BID group did not. Higher cord ferritin concentrations were correlated with larger negative slow waves at the right temporal (T4) electrode site. At 1 y of age, motor development was slower in the BID group than in the BIS group. IDMs suspected to have BID demonstrated impaired neonatal auditory recognition memory and lower psychomotor developmental scores at 1 y of age than IDMs with BIS. These impairments map onto areas of the developing brain known to be vulnerable to iron deficiency.

Monitoring of early postnatal glucose homeostasis and cerebral function in newborn infants of diabetic mothers. A pilot study.

The aims of this pilot study were to evaluate a new technique in the monitoring of postnatal glucose homeostasis (microdialysis) and also to study possible associations between early postnatal hypoglycaemia and influences on cerebral function monitoring (CFM) in 12 newborn infants of diabetic mothers. In order to study the postnatal glucose homeostasis, frequent dialysate samples were obtained from a subcutaneous microdialysis catheter for measurements of glucose. In addition, we also received samples of dialysate lactate and glycerol. Dialysate glucose concentrations were correlated to capillary blood glucose levels, measured by a glucose oxidase method. The cerebral function monitor was applied postnatally and a registration was obtained continuously. Capillary blood glucose decreased initially, and seven newborns received intravenous glucose infusions due to glucose concentrations less than 2.2 mmol/l. Dialysate glucose concentrations were, on average, 0.4 mmol/l higher than corresponding concentrations in capillary blood. The correlation coefficient between the two measurements was 0.63 and the coefficient of variation was 19.2%. Dialysate lactate and glycerol levels increased significantly, with peak values 3-4 h postnatally. No significant overall influence of hypoglycaemia was detectable in the CFM tracing. We conclude that a relatively poor correlation was observed between glucose measurements in capillary samples and microdialysis. However, using the microdialysis technique saw indication of marked lipolysis and increased lactate production, which may be of importance for cerebral postnatal adaptation. The mild postnatal hypoglycaemia in infants of diabetic mothers does not seem to give visually detectable influences on CFM.

Leptin Concentrations Are Elevated in Newborn Infants of Diabetic Mothers

Background: Infants of diabetic mothers have been characterized by macrosomia due to hyperinsulinism. A relation has been observed between circulating levels of leptin and the intrauterine growth pattern. Methods: We studied the leptin and insulin concentrations in the cord blood of 29 newborn infants of mothers with type 1 diabetes (iT1DM), 70 newborn infants of mothers with gestational diabetes and 105 newborn infants of nondiabetic mothers. Results: There were significant differences (p < 0.001) between the 3 groups with the highest leptin levels 24.9 µg/l (range 1.7–94.1) in infants of mothers with iT1DM and the second-highest levels 14.0 µg/l (range 2.6–74.9) in infants of mothers with gestational diabetes (iGDM), whereas the control infants had the lowest leptin levels 10.0 µg/l (range 0.10–45.9). Girls had higher leptin concentrations than boys among the iT1DM and control infants. The insulin concentrations were 18.1 mU/l (range 1.9–123.3), 6.1 mU/l (range 1.1–51.4) and 3.6 mU/l (range 0.5–21.5) in the 3 groups (p < 0.001), respectively. A significant correlation was observed between leptin and insulin concentrations in iGDM and control infants (r = 0.51; p < 0.001 and r = 0.25; p < 0.05). Both absolute and relative birth weights correlated with leptin levels in all 3 groups (r = 0.60, p = 0.01 and r = 0.51, p = 0.05 in iT1DM; r = 0.51 and 0.56, p < 0.001 in iGDM and r = 0.42 and 0.59, p < 0.001 in control infants). Conclusion: Our results confirm the relation between leptin concentrations and birth weight. They also suggest that leptin may be involved in the increased accumulation of adipose tissue characteristic of infants of diabetic mothers.

Auditory Brain Maturation and Recognition Memory in Newborn Infants of Diabetic Mothers 1237

Infants of diabetic mothers (IDMs) are at increased risk for cognitive impairments, possibly due to alterations in fetal brain growth and development. The purpose of this longitudinal study is to evaluate the neural bases of cognitive impairments in IDMs. In this first phase, we evaluated neonatal brain function in 21 IDMs studied at term and compared with 22 full term healthy control infants using event-related potentials (ERPs). The ERP technique is an electrophysiologic method which can be used to study regional brain maturation and cognitive function.

Neurophysiologic assessment of auditory recognition memory in newborn infants of diabetic mothers

The preferential expression of T-cell receptor (TCR) Vα regions in the CD4+ and CD8+ T-cell subsets suggests that they have a special role in distinguishing recognition of major histocompatibility complex (MHC) class I from class II, or CD4 from CD8. Here, Bee-Cheng Sim, David Lo and Nicholas Gascoigne review recent data indicating the molecular basis for this discrimination, and how polymorphism within Vα subfamilies and between TCR α-chain haplotypes contributes to the T-cell repertoire.

Increased muscularization of small pulmonary arteries in preterm infants of diabetic mothers: a morphometric study in noninflated, noninjected, routinely fixed lungs.

We attempted to identify a structural correlate of the pulmonary hypertension observed in newborn infants of diabetic mothers (IDM) by performing a morphometric analysis of pulmonary arteries at the transition of terminal to respiratory bronchiolus (TRB) in postmortem lungs of 20 IDM and 14 control infants. Although there was no readily apparent microscopic difference between the lungs of newborn IDM and controls, the degree of muscularization, as measured by mean medial area (MMA) of 10 TRB arteries, was significantly greater in preterm IDM (gestational age < or = 37 weeks) than in age-matched controls (502 versus 341 microns 2; P = .0038). Among infants of gestational age > 37 weeks, there was no significant difference between MMA in IDM (508 microns 2) and MMA in controls (598 microns 2). These findings point at an accelerated muscularization of the TRB arteries in IDM, apparent early in the third trimester. The pathogenesis of this hypermuscularization is not understood, but smooth muscle growth promoters such as insulin may play a role. The abnormal timing of TRB artery muscularization could be a manifestation of the basic disturbance in development that contributes to the pulmonary hypertension observed in newborn IDM and to the respiratory difficulties commonly experienced by these infants.

Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers

Infants of diabetic mothers frequently have polycythemia, elevated serum erythropoietin concentrations, and decreased serum iron and ferritin concentrations, likely representing a redistribution of fetal iron into erythrocytes to support augmented fetal hemoglobin synthesis. We hypothesized that fetal liver, heart, and brain iron concentrations are also reduced in these infants. After obtaining autopsy tissue from infants who had died before 7 days of age, we measured liver, heart, and brain iron concentrations using atomic absorption spectrophotometry. Seven infants of diabetic mothers and seven gestational age-matched control infants were studied. All infants of diabetic mothers had pancreatic islet cell hyperplasia, indicating fetal hyperglycemia and hyperinsulinemia. Liver iron concentrations in the infants of diabetic mothers were 6.6% of control values (489.0 +/- 154.4 vs 7379.7 +/- 1473.8 micrograms/gm dry tissue weight (mean +/- SEM); p less than 0.001), heart iron concentrations were 43.9% of control values (124.7 +/- 20.5 vs 284.1 +/- 34.8 micrograms/gm dry tissue weight; p less than 0.002), and brain iron concentrations were 60.6% of control values (106.1 +/- 13.7 vs 175.2 +/- 10.7 micrograms/gm dry tissue weight; p less than 0.003). Heart and brain iron concentrations were directly correlated with liver iron concentrations (r = 0.80 for both; p less than 0.001) and indicated that hepatic iron was greater than 75% depleted before heart and brain iron reduction. We conclude that severely affected infants of diabetic mothers have reduced liver, heart, and brain iron concentrations. The role of tissue iron deficiency in the genesis of the abnormal clinical findings in these infants deserves further consideration.

The Effect of In Utero Insulin Exposure on Tissue Iron Status in Fetal Rats

Newborn infants of diabetic mothers have serum biochemical signs of iron deficiency in cord blood directly related to elevations of cord erythropoietin and Hb concentrations. In sheep, chronic fetal hyperinsulinemia results in fetal hypoxemia, expansion of the red cell mass, and decreased iron concentrations, most likely due to increased iron utilization for Hb synthesis. To determine whether fetal insulin exposure also results in reduced tissue iron concentrations, we measured liver, skeletal muscle, small intestine, heart, and brain iron concentrations in newborn rat pups after s.c. fetal injection of insulin or diluent alone on d 19 of gestation. The fetuses of 11 pregnant rats were exteriorized, injected with 2 U neutral protamine Hagedorn insulin or diluent, replaced in utero, and delivered on d 22. To determine dose dependency, the fetuses of six pregnant rats were injected with 3 U of longer-acting protamine zinc insulin and delivered on d 21. At delivery, the insulin-treated groups had higher birth weights than the placebo-treated group, although plasma insulin concentrations were not different. The 2 U neutral protamine Hagedorn insulin-treated fetuses had significantly lower mean +/- SEM liver iron concentrations than the control fetuses (910 +/- 34 versus 1014 +/- 43 micrograms/g dry tissue weight; p less than 0.05), but had similar skeletal muscle iron concentrations. The 3 U protamine zinc insulin-treated fetuses had significantly lower liver and skeletal muscle iron concentrations compared to control and to 2 U neutral protamine Hagedorn insulin-treated fetuses (p less than 0.05). No differences in small intestine, heart, or brain iron concentrations were seen among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Infants of diabetic mothers: a prospective study of neonatal complications in Harare, Zimbabwe

Complications in 42 newborn infants of diabetic mothers (IDM), both insulin- and non-insulin-dependent, were studied prospectively over a period of 16 months at Harare Maternity Hospital. Hypoglycaemia, the most common complication observed, was present in 23 (55%): only seven of these were symptomatic. In 21 of these 23 cases, blood glucose was stabilized during the first 24 hours of life. Jaundice and transient tachypnoea were each seen in 12 cases (29%). There were no cases of respiratory distress syndrome. One infant had polycythaemia requiring partial exchange transfusion. No life-threatening congenital malformations were seen. All infants were given special care initially and in the majority of cases this could be discontinued after 24 hours. With simple interventions, the morbidity of IDM born was found to be comparable to levels reported from developed countries.

Significant decrease in congenital malformations in newborn infants of an unselected population of diabetic women

In an unselected and consecutive series of 1858 newborn infants of diabetic mothers, born in the Rigshospital, Copenhagen, in the period 1967 to 1986, congenital malformations were studied. The malformation rate in White Classes B to F was remarkably constant from 1967 to 1981, but a significant decrease in major congenital malformations was found in the period 1982 to 1986 versus 1977 to 1981 (2.7% vs. 7.4%, p less than 0.05). This decrease was mainly due to a fourfold decline in major congenital malformations in White Classes D and F (p less than 0.01), and consequently a correlation between the severity of maternal diabetes and the frequency of congenital malformations was no longer present. In the offspring of a control group of 1715 nondiabetic women, major congenital malformations were found in 1.7% (p greater than 0.05). Seventy-five percent of the diabetic pregnancies were planned, and in these pregnancies only 1% of the infants had major congenital malformations. The frequency of fatal malformations in White Classes B to F was still significantly higher than in the control group (p less than 0.001).

Cord transferrin and ferritin values for erythropoiesis in newborn infants of diabetic mothers.

Neonatal polycythemia is a perinatal complication in infants of diabetic mothers. The cord CBC (complete blood counts), serum iron, transferrin and ferritin concentrations were studied in newborn infants of 9 GDM (gestational diabetes), 21 NIDDM (noninsulin-dependent diabetes mellitus), and 8 IDDM (insulin-dependent diabetes mellitus) mothers. The RBC (red blood cell) count, Hb (hemoglobin) and Hct (hematocrit) of these infants were higher than control infants. There was no difference between the serum iron concentration of the infants of each group diabetic mothers and the infants in the control group, but the transferrin concentration was significantly higher and the ferritin was significantly lower in the infants of diabetic mothers than in those of control mothers. There was a significant negative correlation between transferrin and ferritin (r = -0.491 p less than 0.001). Erythropoiesis is considered to be enhanced in the fetuses of diabetic mothers, and the iron needed for erythropoiesis is reportedly transported from the mother to the fetus according to the demands of the fetus, but the iron storage was shown to be reduced in the fetuses of diabetic mothers.

13 MATURATION OF THE HORMONAL ENTEROINSULAR AXIS IN NEW-BORN INFANTS OF INSULIN-TREATED DIABETIC MOTHERS

To study whether the increased glucose levels in the amniotic fluid during diabetic pregnancies induce an early maturation of the hormonal enteroinsular axis we measured blood glucose (BG) levels and plasma concentrations of C-peptide (CP), pancreatic glucagon, enteroglucagon (EG) and gastric inhibitory polypeptide (GIP) before and after the first feed in 20 newborn infants of diabetic mothers (IDM) and 12 infants of nondiabetic mothers. All infants were given their first feed comprising human milk (5 ml/kg) by a nasogastric tube at the age of 2 hours. Blood samples were taken before and at 5, 30, 60 and 120 minutes after feeding. At the beginning the IDM had significantly lower BG levels, higher CP and lower EG concentrations. There was a significant increase in BG levels in both groups after the feed and 2 hours after feeding the BG concentrations were of the same magnitude in both groups. No significant CP response could be observed in either of the groups but the IDM had significantly higher C-peptide concentrations at all time points studied. A significant EG and GIP response could be seen in the IDM but not in the controls. However, we did not find any significant differences between the two groups in the absolute plasma concentrations of these two hormones. Our results show that enteral feeding with human milk corrects the early postnatal hypoglycemia within 2 hours in most IDM without causing any exacerbation of their hyperinsulinemia. The absence of any differences in the absolute concentrations of GIP and EG in the peripheral circulation after the first feed suggests that the enteroinsular axis matures postnatally in IDM as well as in normal infants.

Treatment of emergency cases in newborn infants of diabetic mothers.

Some of the most common complications seen in newborn infants of diabetic mothers are reported in this paper. These include hypoglycaemia, hypocalcaemia, hyperbilirubinaemia, polycythaemia, respiratory distress syndrome and cardiac failure. Recent pathogenetic views and therapeutic schedules are discussed.

Estimation of urine specific gravity in neonates with a reagent strip

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