CORD BLOOD HAEMOGLOBIN, IRON AND FERRITIN STATUS IN MATERNAL ANAEMIA

ABSTRACT. Maternal and cord blood haemoglobin, serum iron, transferrin saturation and ferritin were studied in sets of 30 anaemic (haemoglobin <110 g/l) and 21 nonanaemic (haemoglobin ≧110 g/l) mothers. The cord serum iron, transferrin saturation and ferritin concentrations had significant correlation with maternal haemoglobin. The significant low levels of these parameters suggested that maternal anaemia adversely affected the iron status including iron stores of the newborns. The cord serum iron of 15.2±4.35 μmol/l and ferritin of 29.7±10.93 ng/ml seem to be effective to maintain cord haemoglobin levels. Thus, anaemic mothers with reasonably maintained ferritin and trasferrin saturation levels provide sufficient iron for maintenance of cord haemoglobin, although foetal iron stores are likely to be depleted.     

Haemolysis in adult and neonatal erythrocytes caused by autoxidation of lipid emulsion (Intralipid)

Lipid emulsion (Intralipid) causes free radical-mediated damage to human cells in vitro. Incubation with 0.44% Intralipid for 17 h caused 40.3 ± 3.8% haemolysis in adult human erythrocytes and 26.5 ± 8.1 % in erythrocytes from term newborns ( p = 0.0001). In adult erythrocytes mean corpuscular volume increased 68.7 ± 8.20%, and in newborn erythrocytes 54.8 ± 10.4% ( p = 0.0012). Initial concentrations of reduced glutathione in adult and newborn erythrocytes were 65.1 ± 2.5 and 62.1 ± 4.0 mg/dl, respectively (ns); after incubation, glutathione concentrations were 21.0 ± 4.0 and in 25.7 ± 5.2 mg/dl in adult and newborn erythrocytes, respectively ( p = 0.0004). After incubation the concentrations of thiobarbituric acid reactive material and conjugated dienes in newborn erythrocytes (2.8 ± 0.2 μM and 0.223 ± 0.019 OD 233, respectively) were higher than those of adult erythrocytes (2.1 ± 0.4 μM and 0.138 ± 0.012 OD 233) ( p = 0.0001). In both adult and newborn erythrocytes, the effects of Intralipid were significantly inhibited by 0.6 mM desferoxamine or 8 mM sodium etidronate. Despite higher susceptibility to lipid peroxidation of the cell membrane, newborn erythrocytes are more resistant than adult erythrocytes to free radical-mediated effects such as depletion of intracellular glutathione, cell swelling and haemolysis.     

Brainstem auditory evoked responses in term small for gestational age newborn infants born to undernourished mothers.

Our aim was to assess the effect of intrauterine growth retardation on neurosensory development by evaluating brainstem auditory evoked responses (BAER) in term small for gestational age (SGA) newborn infants born to undernourished mothers. This prospective clinical study included 25 singleton healthy SGA newborn infants born between 38 and 41 weeks to undernourished mothers (weight <45kg, height <145cm, haemoglobin <8g/dl, and serum albumin <2.5g/dl). An equal number of age- and sex-matched appropriate for gestational age newborn infants born to healthy mothers served as controls. Mothers with other risk factors and newborns with complications during delivery or immediate newborn period were excluded. BAER was recorded within first 3 days of life. Interpeak latency (IPL), absolute peak latency (APL) and amplitudes of various waveforms were determined and compared between the groups.No statistically significant differences were observed for the mean interpeak and absolute latencies between term SGA and AGA infants (p>0.05). The absolute peak latency (wave V) and central conduction time (I-V interval) were borderline prolonged in the study group compared with controls (p=0.051 and 0.088 respectively). Using multiple regression analysis, maternal haemoglobin was identified to be the only parameter having a negative correlation with both IPL (waves I-V) (F[1,46]=4.12, p=0.048) and APL (wave V) (F[1,46]=5.80, p=0.02). Maternal undernourishment may have a minor effect on intrauterine development of the auditory brainstem. Maternal haemoglobin is the only factor significantly associated with these changes.     

Leptin and metabolic hormones in infants of diabetic mothers

AIMS: To investigate the effect of maternal diabetes on leptin in term newborns and to determine whether leptin correlates with insulin and its associated biochemical parameters in support of the hypothesis that a functional "adipoinsular axis" might exist at this stage of development. METHODS: A total of 116 term newborns were prospectively enrolled and categorised into three groups: 44 were infants of non-diabetic mothers (control group C); 41 were infants born to mothers with gestational diabetes on dietary treatment (group D); and 31 were infants born to mothers with gestational or pregestational diabetes on insulin treatment (group I). RESULTS: No significant difference in serum leptin was observed between the three groups; the results of the study population were therefore pooled and analysed. Serum leptin correlated significantly with serum insulin, insulin:glucose ratio, birth weight, body length, body mass index, placenta weight, and maternal HbA(1c). Female infants had significantly higher serum leptin than male infants. All parameters except placenta weight and body length remained significantly associated with serum leptin when multivariate stepwise regression analysis was applied. Subgroup analysis revealed a significant correlation between serum leptin and cortisol in group D. CONCLUSIONS: There was no significant difference in serum leptin between infants born to diabetic and non-diabetic mothers, though infants born to mothers requiring insulin treatment had the highest median serum leptin concentrations. The significant association between serum leptin and insulin or insulin:glucose ratio supports the hypothesis that a functional adipoinsular axis might exist in term newborns. Furthermore, the significant correlation between maternal HbA(1c) and circulating leptin of the studied infants suggests that the clinical control of maternal diabetes could affect the regulation of serum leptin in these infants.     

Disorders in Glucidic Metabolism and Congenital Heart Diseases: Detection and Prevention

The identification of gestational diabetes (GDM) through appropriate screening and its subsequent treatment have not been demonstrated to limit neonatal malformations to date. This study aimed to detect congenital heart diseases in newborns of mothers with GDM by evaluating the existence of a correlation with maternal glycemic control. This observational prospective study investigated newborns of mothers with GDM enrolled during a period of 9 months. Four subgroups were considered according to the type of maternal glucidic alteration during pregnancy and the home treatment: impaired glucose tolerance, insulin-dependent gestational diabetes mellitus (IDDM), non-insulin-dependent gestational diabetes mellitus (NIDDM), and gestational diabetes not controlled (NC: untreated diabetes). Student’s t test was used to compare the subgroups. The study enrolled 65 newborns (30 boys) born to 82 of mothers with impaired glucidic metabolism. Patent ductus arteriosus was observed in 11 patients (16.9 %), pulmonary stenosis of mild grade in 4 patients ( 6.2 %), and hypertrophy of the ventricular septum in 22 patients (33.8 %). A total of 14 patients had increased thickness in the left ventricle posterior wall, and 17 patients had an abnormal electrocardiogram. Hyperglycemia can influence the development of the fetal heart, affecting both its structure and its function. A treatment with insulin for women with GDM is supported by the study data.     

Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes

Diabetes during pregnancy may be associated with a high rate of congenital anomalies, disturbances of intrauterine growth and often post-natal neurobehavioral abnormalities in the offspring. The latter are associated with pregestational (PGD) as well as with gestational diabetes (GD). In this review we discuss the effects of maternal glucose intolerance on the long-term growth and development of the offspring. In well-controlled diabetes, birth weight is often within normal limits while in partially controlled diabetes newborns are often macrosomic. In PGD mothers with nephropathy, newborns tend to be born prematurely and small for gestational age (SGA). Offspring of diabetic mothers are often large and overweight in comparison to controls. Their long-term development is sometimes impaired. Delayed brain maturity is often observed in newborns of diabetic mothers compared to controls. The IQ scores of the children born to well controlled diabetic mothers are generally similar to that of control children. However, these children perform less well than controls in fine and gross motor functions. They also seem to have a higher rate of inattention and/or hyperactivity as observed by various tests and questionnaires. In our studies we found, in accordance with published literature, a negative correlation between the performance of the children born to mothers with PGD or GD on various neurodevelopmental and behavioral tests and the severity of maternal hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. In conclusion: PGD or GD may adversely affect intrauterine and postnatal growth, attention span and motor functions of the offspring, but not their cognitive ability unless complicated by nephropathy or hypertension. These effects are negatively correlated with the degree of maternal glycemic control.     

Erythrocyte cupric/zinc superoxide dismutase exhibits reduced activity in preterm and low-birthweight infants at birth

In a comparative study in term, preterm and low-birthweight infants, the mean activity and standard error of the mean for copper/zinc superoxide dismutase (Cu/Zn SOD) in cord erythrocytes from five term small for gestational age infants was 0.94 ±0.10 SOD units (mg protein)⁻¹. This value was significantly lower than the activity (2.34 ± 0.24) in nine term, appropriate for gestational age (AGA) babies ( p < 0.005). In 15 preterm (AGA) infants, the activity at birth (1.05±0.07SOD units (mg protein)⁻) was also significantly lower ( p < 0.001) relative to term AGA babies. An increased level of activity (1.59 ± 0.09) was detected in the red cells of eight preterm AGA infants on their expected date of delivery compared with (0.87 ± 0.06) at birth ( p < 0.001). However, the activity (1.59 ± 0.09) was still lower than that detected in term AGA babies (2.34 ±0.24; p < 0.02). Similar findings were obtained when enzymatic activity was expressed in units per millilitre of packed erythrocytes. The low activity of Cu/Zn SOD in preterm and low-birthweight babies may render them susceptible to diseases associated with membrane lipid peroxidation.     

CORD BLOOD PORPHYRINS A Quantitative Assay in Newborn Infants

Abstract. A quantitative assay of free erythrocyte porphyrins was done in umbilical cord blood of 30 newborn babies by a spectrophotometry method. The mean value of free erythrocyte protoporphyrin in umbilical cord blood was found to be 74.58 μg/100 ml packed erythrocytes and that of free erythrocyte coproporphyrin to be 0.77 μg/100 ml packed erythrocytes with a standard deviation of ±29.99 and ±1.48 respectively. Relationship between free erythrocyte protoporphyrin and free erythrocyte coproporphyrin and their correlations with birth weight and sex of the newborn baby were found to be statistically significant.     

Oxidative stress in term small for gestational age neonates born to undernourished mothers: a case control study

Background  

The objective of this study was to assess the status of oxidative stress in term small for gestational age (SGA) newborn infants born to undernourished mothers by estimating levels of erythrocyte superoxide dismutase (SOD), catalase, reduced glutathione, and serum malondialdehyde (MDA) in cord blood and comparing them to healthy appropriate for gestational age (AGA) controls. This was done in a case control design at a tertiary level teaching hospital.     

Foetal haemoglobin concentration in cord blood in relation to gestational age

Summary Eighty newborns of various birth weights and gestational age ranging from 28 to 45 weeks were studied. There were 26 preterm, 41 term and 13 post-term infants. The average values of total and foetal haemoglobin in males and females were studied and there was no significant difference in the two sexes. Total haemoglobin tended to rise with advancing gestation. On the contrary, foetal haemoglobin showed a gradual fall with advancing gestational age. Correlation between gestational age and birth weight and foetal haemoglobin could not be established. Foetal haemoglobin in preterm, term and post-term newborns was 83.93, 68.59 and 60.03% respectively. It was concluded that foetal haemoglobin can be used as one of the indices for determining the maturity. From the Department of Paediatrics, M.G.M. Medical College, Indore.     

Perinatal risk factors and intraventricular hemorrhage in newborn infants of birth weight less than or equal to 1,500 g

In a retrospective study in 113 preterm newborns (birth weight less than or equal to 1500 g, gestational age less than 35 weeks) intraventricular hemorrhage (IVH I-IV) determined by serial sonographic examinations was correlated to a number of maternal and neonatal risk factors. While there was no significant correlation to bleeding during the gestation, premature rupture of the membranes, mode of delivery, and age of the mother, incidence of IVH was significantly lower in newborns born to mothers with EPH-gestoses (p less than 0.05). A significant high incidence of IVH was found in very premature newborns (p less than 0.025) and in newborns with hyaline membrane disease (p less than 0.005). No single risk factor for a high incidence of IVH was found. IVH in very low birth weight infants probably is caused by summation of several different perinatal risk factors.     

Studies on maturity in newborn infants. VII. Foetal haemoglobin.

Cord blood from 125 newborns of various gestational ages has been analysed for the ratio foetal haemoglobin to total haemoglobin, using an alkali denaturation method. The quotient, percentage of foetal haemoglobin divided by birth weight correlates well with gestational age. Thus the percentage of foetal haemoglobin in cord blood can be used as a method for estimating maturity in newborn infants. Foetal haemoglobin has been compared with other methods for maturity assessments and seems to give the same precision in estimating gestational age as the best of these, which is the scoring of external characteristics. However, the latter method is considerably less time-consuming and more suitable for routine use.     

Preterm birth and maternal smoking in pregnancy are strong risk factors for aortic narrowing in adolescence

AIM: Preterm transition from foetal to neonatal circulation might permanently alter aortic growth and development. To test this hypothesis, we measured aortic dimensions in adolescents born very preterm. METHODS: Eighty-six healthy 15-year-old subjects were studied; 45 born very preterm at an average gestational age of 28 weeks (birth weight < 1500 g) and 41 controls born at term. Using a pulse-gated Fiesta sequence on a 1.5T MR-scanner, 25 images were collected within the heart cycle at several levels of the descending aorta. End-diastolic cross-sectional areas were semi-automatically calculated using an active contour model. RESULTS: Subjects born preterm had narrower aortic lumen. The difference was 16% in the thoracic and 19% in the abdominal aorta after adjustment for body surface area and gender (p < 0.001). Maternal smoking in pregnancy was also found to be an independent risk factor for aortic narrowing in the offspring (difference 10%-13% throughout the aorta vs. offspring to nonsmoking mothers). Adolescents born preterm had higher systolic and diastolic blood pressures; however, blood pressures did not correlate with aortic size or maternal smoking during pregnancy. CONCLUSION: Very preterm birth and exposure to maternal smoking in foetal life are independent and strong risk factors for general aortic narrowing 15 years after birth.     

Long-term effects of diabetes during pregnancy on the offspring

Background: Many epidemiological and experimental studies have proven that some adult diseases might have their origin in fetal life. It has been also hypothesized that intra-uterine environment in pregnancy complicated with diabetes might influence the development of obesity, type 2 diabetes, and cardiovascular diseases in the offspring.
Objectives: To assess glucose metabolism, insulin secretion, and prevalence of obesity in the offspring of mothers with pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) and to evaluate the relationship between maternal metabolic control during pregnancy and metabolic disturbances in children.
Subjects: Children of mothers with PGDM (n = 43) and GDM (n = 34) were examined at 4–9 yr of age and compared with the control group (n = 108; metabolic parameters available for n = 29).
Methods: The incidence of overweight and obesity, impaired glucose tolerance, and insulin resistance were analyzed based on anthropometric and biochemical measurements. Statistical analysis was performed with statistica package.
Results: In children of GDM mothers, body mass index z-score (0.81 ± 1.01 vs. −0.04 ± 1.42 PGDM vs. 0.07 ± 1.28 control group) and insulin resistance indices (homeostasis model assessment index – insulin resistance 1.112 vs. 0.943 PGDM vs. 0.749 control group) were significantly higher than in other groups. Obesity and insulin resistance were also most frequent in GDM group [not significant (NS)]. In addition, we observed the relationship between maternal hemoglobin A1c and mean glycemia in perinatal period and insulin resistance in children. There was not such correlation for the class of maternal diabetes.
Conclusion: Children born to mothers with gestational diabetes seem to be at risk for obesity and metabolic disturbances.     

PLASMA AND ERYTHROCYTE ZINC, COPPER AND SELENIUM IN CYSTIC FIBROSIS

ABSTRACT. Plasma and erythrocyte zinc, copper and selenium were measured in 20 cystic fibrosis children, aged 7 to 19 years. Mean plasma zinc and copper levels were not different from those in age-matched controls but very low zinc levels occurred sporadically. Plasma zinc concentrations were significantly lower in patients with moderate-to-severe growth retardation and with severe pulmonary disease as compared to patients without growth failure and with moderate pulmonary disease. Mean erythrocyte zinc (40.8 μg/g Hb ±9.2) and copper levels (3.56 μg/g Hb ±0.50) were very significantly increased (30.4 μg/g Hb ±5.2 and 2.73 μg/g Hb ±0.30 respectively, for age-matched controls). Mean plasma and erythrocyte selenium levels (63 ng/ml ±15 and 329 ng/g Hb ±86) were significantly lower than those in age-matched controls (82 ng/ml ±13 and 404 ng/g Hb ±116). The trace element concentrations in erythrocytes are discussed in relation to the activities of the copper- and zinc-containing enzyme superoxide dismutase and the seleno-enzyme glutathione peroxidase. We consider that more data on trace element metabolism in CF should be collected before specific supplementation is considered.     

STUDIES ON MATURITY IN NEWBORN INFANTS

ABSTRACT: Finnström, O., Gothefors, L. and Zetterlund, B. (Departments of Paediatrics, University Hospitals, Linköping and Umeå, Sweden). Studies on maturity in newborn infants. VII. Foetal haemoglobin. Acta Paediatr Scand, 64:404, 1975.–Cord blood from 125 newborns of various gestational ages has been analysed for the ratio foetal haemoglobin to total haemoglobin, using an alkali denaturation method. The quotient, percentage of foetal haemoglobin divided by birth weight correlates well with gestational age. Thus the percentage of foetal haemoglobin in cord blood can be used as a method for estimating maturity in newborn infants. Foetal haemoglobin has been compared with other methods for maturity assessments and seems to give the same precision in estimating gestational age as the best of these, which is the scoring of external characteristics. However, the latter method is considerably less time-consuming and more suitable for routine use.     

Increased lipid peroxidation in children with autoimmune diseases

To examine the role of oxidative damage in children and adolescents with autoimmune diseases, we compared blood serum levels of the lipid peroxidation (LPO) products 4-hydroxynonenal (HNE) and malondialdehyde (MDA) in 22 children with systemic lupus erythematosus (SLE), 13 children with focal type of scleroderma, and 21 healthy controls. In order to study the influence of disease activity in SLE on serum LPO product levels, the SLE group was divided into one group with active disease ( n = 11) and one group with non-active disease ( n = 11) according to SLEDAI-score, 15.1 and 1.8, respectively. SLE patients with active SLE (146 ± 14nmol/l, median 145nmol/l) have significantly higher HNE levels compared to controls (61 ± 10nmol/l, median 52nmol/l), whereas the MDA serum levels are similar to those of the control group, 1.94 ± 0.18μmol/l (median: 2.02μmol/l) and 1.58 ± 0.11 μmol/1 (median: 1.52 μmol/l), respectively. Children with SCL had HNE and MDA levels similar to the control group.     

Storage Iron in Human Foetal Organs

ABSTRACT. Maternal plasma iron and storage iron (non-heme) in the foetal liver were estimated in 108 foetuses whose gestational ages ranged from 12–44 weeks. Simultaneous estimations of storage iron were also made on the spleen and kidney in 70 and 69 of these foetuses respectively. Although the concentration of iron per g wet tissue in these organs remained practically the same at all gestations, the total storage iron content increased with the increase in gestation due to growth of these organs. The liver, in particular, showed a steep rise in total iron content in the last 8 weeks of gestation. There was a significant positive correlation between the total storage iron content in the foetal organs and the birth weight and gestational age of the foetus, suggesting that the preterm infants had smaller iron stores at birth as compared to infants born at term. The direct relation of the concentration as well as the total content of storage iron in the foetal liver with the maternal plasma iron levels suggested that babies born to iron deficient mothers had poor iron stores in their livers.     

Storage iron in human foetal organs

Maternal plasma iron and storage iron (non-heme) in the foetal liver were estimated in 108 foetuses whose gestational ages ranged from 12-44 weeks. Simultaneous estimations of storage iron were also made on the spleen and kidney in 70 and 69 of these foetuses respectively. Although the concentration of iron per g wet tissue in these organs remained practically the same at all gestations, the total storage iron content increased with the increase in gestation due to growth of these organs. The liver, in particular, showed a steep rise in total iron content in the last 8 weeks of gestation. There was a significant positive correlation between the total storage iron content in the foetal organs and the birth weight and gestational age of the foetus, suggesting that the preterm infants had smaller iron stores at birth as compared to infants born at term. The direct relation of the concentration as well as the total content of storage iron in the foetal liver with the maternal plasma iron levels suggested that babies born to iron deficient mothers had poor iron stores in their livers.     

In vitro and in vivo effects of erythrocyte phototherapy on newborns

The photodynamic action of the bilirubin is associated with severe consequences observed during 'in vitro' irradiation of the erythrocytes. This paper is designed to evaluate the bilirubin photodynamic effects which occur 'in vitro' and 'in vivo' on erythrocytes in healthy and jaundiced infants. The in vitro bilirubin sensitized photoreaction damages the erythrocytes mainly at the membrane level. In particular, a dramatic decrease of ATPase activity and an increased susceptibility to lipid peroxidation, expressed as malondialdehyde production, were observed. For in vivo studies, specific fluorescent probes have been used to verify probable changes on the functional architecture of the erythrocyte membrane in the phototherapy-treated infants. Our results showed that specific areas of the membrane are differently affected, mainly at lipid/protein interface. Although the role of the erythrocyte membrane is an important factor of the hemorheological behavior, the measurement of blood viscosity and erythrocyte aggregation and filtration did not show significant alterations during the overall time of phototherapy.