Noirin Russell

Effect of pregestational diabetes mellitus on fetal cardiac function and structure.

OBJECTIVE Fetuses of diabetic pregnancy experience cardiomyopathy, the intracardiac cause of which is understood poorly. The aim of this study was to assess the interrelation between cardiac functional and structural changes in fetuses of mothers with pregestational diabetes mellitus. STUDY DESIGN Twenty-six mothers with pregestational diabetes mellitus were recruited prospectively to have a fetal echocardiogram at 13, 20, and 36 weeks of gestation to assess cardiac function and structure. For comparison, 30 healthy control subjects were recruited at each gestational age. RESULTS In the first trimester, there was evidence of poorer fetal cardiac diastolic function among the diabetic cohort (lower left early/atrial ratio, longer isovolumetric relaxation time and higher left myocardial performance index; P < .05). In the third trimester, the fetal interventricular septum and the right ventricular free wall were thicker in the diabetic cohort (P < .05). CONCLUSION In fetuses of pregestational diabetic pregnancy, sonographic evidence of altered cardiac function is evident before ultrasound evidence of cardiac structural changes. This suggests that altered cardiac function may precede cardiac structural changes in fetuses of pregestational diabetic pregnancy.

Cardiomyopathy and cardiomegaly in stillborn infants of diabetic mothers.

To report the incidence of cardiomegaly in stillborn normally formed infants of mothers with diabetes mellitus. This is a retrospective study with institutional ethics approval. The presence of cardiomegaly was recorded in stillborn infants of diabetic mothers (N = 27) and compared with that recorded in stillborn large-for–gestational age (LGA > 90th percentile, n = 18) and stillborn appropriately grown (10th to 90th percentiles, n = 107) nondiabetic infants. Blinded to the clinical details, the histology slides were reviewed to measure cardiac wall thickness and to record the presence or absence of myocardial fiber disarray. Stillborn infants of mothers with diabetes mellitus, when compared with appropriately grown stillborn nondiabetic infants and when adjusted for birth weight, had heavier hearts, thicker ventricular free wall measurements, and lighter brains. While cardiomegaly was reported in 22% of stillborn LGA infants, comparison with stillborn appropriately grown infants revealed no difference in heart weights corrected for birth weight. Comparison of LGA nondiabetic infants with stillborn diabetes mellitus infants revealed greater actual heart weight/expected for birth weight (P < 0.05) and lighter brains (actual brain weight/expected for birth weight, P < 0.05) in the diabetes mellitus group. Cardiomegaly is a common finding in stillborn infants of mothers with diabetes mellitus and may contribute to the risk of fetal death in these pregnancies.

Troponin T and Pro-B-Type Natriuretic Peptide in Fetuses of Type 1 Diabetic Mothers

OBJECTIVE Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function. RESEARCH DESIGN AND METHODS This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro–B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester. RESULTS Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05). CONCLUSIONS Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

First-Trimester Fetal Cardiac Function

The purpose of this study was to establish normal values for fetal heart function in the first trimester.

Maternal and fetal placental growth hormone and IGF axis in type 1 diabetic pregnancy.

Aim Placental growth hormone (PGH) is a major growth hormone in pregnancy and acts with Insulin Like Growth Factor I (IGF-I) and Insulin Like Growth Hormone Binding Protein 3 (IGFBP3). The aim of this study was to investigate PGH, IGF-I and IGFBP3 in non-diabetic (ND) compared to Type 1 Diabetic (T1DM) pregnancies. Methods This is a prospective study. Maternal samples were obtained from 25 ND and 25 T1DM mothers at 36 weeks gestation. Cord blood was obtained after delivery. PGH, IGF-I and IGFBP3 were measured using ELISA. Results There was no difference in delivery type, gender of infants or birth weight between groups. In T1DM, maternal PGH significantly correlated with ultrasound estimated fetal weight (r = 0.4, p = 0.02), birth weight (r = 0.51, p<0.05) and birth weight centile (r = 0.41, p = 0.03) PGH did not correlate with HbA1c. Maternal IGF-I was lower in T1DM (p = 0.03). Maternal and fetal serum IGFBP3 was higher in T1DM. Maternal third trimester T1DM serum had a significant band at 16 kD on western blot, which was not present in ND. Conclusion Maternal T1DM PGH correlated with both antenatal fetal weight and birth weight, suggesting a significant role for PGH in growth in diabetic pregnancy. IGFBP3 is significantly increased in maternal and fetal serum in T1DM pregnancies compared to ND controls, which was explained by increased proteolysis in maternal but not fetal serum. These results suggest that the normal PGH-IGF-I-IGFBP3 axis in pregnancy is abnormal in T1DM pregnancies, which are at higher risk of macrosomia.

Heart rate variability in neonates of type 1 diabetic pregnancy.

BACKGROUND Cardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. AIMS Our aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. STUDY DESIGN AND SUBJECTS This was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). OUTCOME MEASURES Heart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. RESULTS Neonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (p<0.05). This altered HRV was significantly related to fetal acidaemia, cord blood glucose values and maternal glycaemic control during pregnancy (p<0.05). CONCLUSION Neonates of pregestational diabetic pregnancy have altered HRV which is related to maternal hyperglycaemia, fetal acidaemia and fetal glycaemia. Exposure of the developing heart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life.

Intrauterine fetal transfusion for red-cell alloimmunisation: a single-centre study over 15 years

Objective To examine perinatal outcomes following intrauterine fetal transfusion (IUT), in a single tertiary fetal medicine unit over a 15-year period. Study design A retrospective analysis of women undergoing IUT in the National Maternity Hospital, Dublin from 1996-2010. Eligible cases were identified from a prospectively collated transfusion register. Cases of alloimmune thrombocytopenia, non-immune hydrops or parvovirus infection were excluded. The cord insertion was the preferred site, with the intra-hepatic vein and free cord reserved for inaccessible cases. All procedures were performed by 2 specialists in fetal medicine. Post-transfusion, women were admitted overnight, with biophysical profile and Doppler indices performed prior to discharge. Results Between 1996 and 2010, 262 IUTs were performed in our unit, of which 244 (93%) were undertaken for red cell alloimmunisation, involving 97 pregnancies. The majority of women (84%) had anti-D antibodies, with a smaller incidence of anti-Kell (12%), anti-c (3%) and anti-E (1%) antibodies. Affected women underwent a median of 3 (IQR 2-4) procedures. In total, there were 3 intrauterine fetal deaths and 4 early neonatal deaths, for a perinatal mortality rate of 7%. The procedure-related loss rate was 1.2% (3/244). Two women had in utero fetal demise within 48 hours of the IUT, at 25 weeks and 29 weeks respectively. The third loss was from a cord haematoma at 32 weeks, with early neonatal demise. Conclusion Intrauterine fetal transfusion is a safe procedure, associated with a low (1%) rate of procedure-related fetal loss, when performed by experienced practitioners in a national referral centre.

Neonatal heart rate variability in type 1 diabetic pregnancy

Introduction In adult diabetic patients, abnormalities in heart rate variability can predict mortality post myocardial infarction. Fetuses of diabetic mothers are at increased risk of unexplained death in utero and it is possible that there may be an association with underlying alterations in fetal autonomic function. The objective of this study is to determine if neonatal autonomic function differs between normal and pregestational type 1 diabetic pregnancy. Methods Thirty-eight patients with pregestational type 1 diabetes mellitus and 26 healthy controls were prospectively recruited. All patients had neonatal heart rate variability assessed using Powerlab (AdiInstruments) and cord blood sampling for arterial and venous pH and glucose was performed. Results Significant differences were found between the two cohorts. In the diabetic cohort, there was increased overall power, increased low frequency (LF), decreased high frequency (HF) with an increased LF:HF ratio, (p values 0.016, 0.016 and 0.042, respectively) reflecting sympathetic over activity. These differences were independent of gestational age and birthweight centile. There were also significant associations between heart rate variability and fetal academia (p=0.01) and maternal and fetal glycaemic control (p<0.05 and p=0.019, respectively). Conclusion This study shows significant evidence of autonomic dysfunction in neonates of type 1 diabetic mothers. This may be related to the effect of prolonged fetal exposure to the hyperglycaemic milieu of diabetic pregnancy. Autonomic dysfunction may have a role in unexplained fetal death as it is influenced by acidosis and hyperglycaemia; features associated with fetal death in pregestational diabetic pregnancy.