Maternal diabetes and neonatal macrosomia. III. Neonatal body water estimates

Body water estimates were obtained within 12 h of birth in 52 infants of non-diabetic mothers and 61 infants of diabetic mothers. Neonates were grouped as normally-grown or macrosomic. Total body water and extracellular water were estimated from antipyrine space and corrected bromide space, respectively. Intracellular water was assumed to be the difference between total and extracellular water. Infants of diabetic mothers, whether normally-grown or macrosomic, had markedly less mean total body water than normally-grown neonates of non-diabetic mothers. No effect of neonatal macrosomia or maternal diabetes on extracellular and intracellular water estimates could be detected with the techniques used. It is suggested that changes in total body water occur as a result of excessive fat accretion during fetal life.     

Effects of maternal smoking on fetal growth and nutrition.

Standard anthropometric measurements were made on 320 term neonates to investigate the influence of smoking on fetal growth and nutrition. Maternal height and triceps skinfold thickness were also measured. Of 320 infants, 126 (39%) were born to mothers who smoked. Maternal triceps skinfold thickness was significantly smaller in smoking mothers. A correlation existed between maternal and infant triceps skinfold thickness. Measurements of infant growth, birthweight, occipito-frontal circumference, and crown-to-heel length were significantly smaller in infants of smoking mothers and remained significantly smaller when corrections were made for maternal triceps skinfold thickness, height, and social class. While these data do not exclude a nutritional mechanism for the effect of maternal smoking on the fetus, the major growth-retarding effects remain after corrections for this. This reduction in occipito-frontal circumference in infants of smoking mothers, and the possible significance of this is stressed.     

Aortic intima-media thickness and lipid profile in macrosomic newborns

Macrosomia is associated with alterations in lipoprotein composition and concentration at birth. Exposure to diabetes in utero has been established as a significant risk factor for some of the components of metabolic syndrome. The aim of this study was to investigate the effect of macrosomia on lipid metabolism, aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 40 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile was determined in all infants and their mothers. Mean aIMT was significantly higher in macrosomic neonates of diabetic and healthy mothers (0.56±0.06 and 0.49±0.03 mm respectively) than in controls (0.39±0.03 mm). Weight-adjusted aIMT in macrosomic neonates of diabetic mothers (0.129±0.013 mm/kg) was significantly higher than in groups B and C (0.114±0.008 and 0.113±0.011 mm/kg respectively). There were significant alterations of total serum, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) cholesterols and triglyceride levels in the macrosomic neonates of diabetic mothers compared with controls. Macrosomia was associated with increased lipid concentrations. Macrosomic neonates of diabetic mothers have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.     

Fetal growth in different racial groups.

Three racial groups of mothers and their newborn babies-- North European 75, Negro 75, and "Indian" Asian 37--were matched for parity, gestational age, sex, maternal age, maternal smoking habits, and social class. Multiple anthropometric measurements, including skinfold thickness, limb circumferences, and various linear measurements were made on the mothers and their infants to determine the effects of race and smoking on fetal size. Indian-Asian mothers, though shorter and lighter than Europeans and Negroes, had similar skinfold thickness and weight: height2 ratios and gained as much weight during pregnancy. Their infants, however, were lighter than the others, and had smaller head and limb circumferences, although their linear measurements were the same. Negro and European infants were almost identical in size. We found no effect on any of the fetal measurements which could be attributed to smoking.     

Ponderal index of large-for-gestational age infants: comparison between infants of diabetic and non-diabetic mothers

Ponderal index (PI) is a weight-height related parameter that is mainly used to assess the pattern of fetal growth in small-for-gestational age infants. We aimed to use PI for large-for-gestational age (LGA) infants who were born to diabetic or non-diabetic mothers, in order to predict the fetal growth pattern. One hundred sixty-six LGA infants born at the Department of Obstetrics, Hacettepe University Hospital, Ankara, Turkey were included in the study. The PI was calculated by using the following formula: PI = weight (g) x 100/(height, cm)3. Sixty-seven (40%) of these infants were born to diabetic mothers. Maternal age, maternal weight and maternal weight gain during pregnancy were similar in the diabetic and non-diabetic groups. Mean birthweight, height and head circumference were similar in both groups, but median PI of infants of diabetic mothers was significantly higher than of infants of non-diabetic mothers (3.02 and 2.89, respectively, p < 0.05). Fetal growth was different between LGA infants of diabetic and non-diabetic mothers, and PI provided useful information on the proportionality of fetal growth in LGA infants.     

Body composition in neonates: relationship between measured and derived anthropometry with dual-energy X-ray absorptiometry measurements

This study examined the relationship between measured and derived anthropometric measurements with dual-energy X-ray absorptiometry measured lean and fat mass at 3.0 +/- 2.8 (SD) days in 120 neonates with birth weights appropriate (AGA; n=74), large (LGA; n=30); or small (SGA, n=16) for gestational age. Anthropometric measurements, including total body weight and length, and regional measurements, including circumferences of head, chest, abdomen, midarm, and midthigh and dynamic skinfold thickness (15 and 60 s) at tricep, subscapular, suprailiac, and midthigh, were performed. Derived anthropometry included muscle and fat areas, and ratios were calculated from direct measurements. The skinfold thickness measurements between 15 and 60 s were highly correlated (r=0.973-0.996, p <0.001 for all comparisons). Strong correlations existed within the four circumferences of trunk and extremities, the four skinfolds, and the ratios of weight to length and its higher powers. Weight and length accounted for >97% of the variance of lean mass in AGA and SGA infants and 46% of the variance in LGA infants and for 80, 82, and 84% of the variance of fat mass in SGA, AGA, and LGA infants, respectively, whereas midarm:head circumference ratio and arm muscle and fat areas are the most important derived anthropometry in the prediction for body composition. They independently accounted for up to 16.5 and 10.2%, respectively, of the variance in body composition depending on the state of in utero growth. Thus, total body weight and length and some selected regional and derived anthropometry accounted for the vast majority of the variance of body composition.     

Judging fetal growth from body proportions at birth.

Fetal growth velocity from 27 weeks until birth was calculated in 378 infants born after high risk pregnancies from at least three ultrasound measurements of estimated fetal weight and the weight at birth. Anthropometric measurements at birth (weight, head circumference, length, ponderal index and skinfolds), after correction for differences in gestational age, were significantly related to fetal growth velocity. The relation between fetal growth velocity and ponderal index was significant (correlation coefficient = 0.34, P < 0.001). However, the correlations between fetal growth velocity and each of the anthropometric measures disappeared when birth weight relative to gestational age was accounted for. This means that given the birth weight and the gestational age of a newborn infant, body proportions, e.g. ponderal index or skinfold thickness, do not contribute further to the judgment about fetal growth rate.     

Follow-up of children of diabetic mothers.

The results of a follow-up study of infants of diabetic mothers are presented. The antenatal care of all such mothers was supervised in a combined clinic by obstetricians and physicians, and good diabetic control was achieved in most of them. 51 mothers delivered 73 infants, all liveborn, between the years 1964 and 1972 inclusive at Hammersmith Hospital. There were no fetal deaths. 66 infants survived the neonatal period, and 63 the first 2 years of life. 51 children, including all those seriously ill in the neonatal period, could be traced. Detailed neurological and general examinations including skinfold measurements were made, and the IQ measured. Four children were found to have major handicaps. These were severe deafness, epilepsy, low IQ, and myopia. No other neurological abnormalities were detected, and the distribution of full-scale IQs was normal. The distribution of height and head circumference centiles was near normal, but an increased number of children had weights above the 90th centile. No significant congenital malformations were found in these 51 survivors, and none has so far developed diabetes.     

Early post-natal growth of large-for-dates babies of non-diabetic mothers is influenced by maternal glucose metabolism

Growth of weight, length, head circumference and skinfold thickness (subscapular and triceps) from birth to 6 months in 53 large-for-dates (LFD) Chinese babies weighing greater than 4.0 kg at term and born to non-diabetic mothers was investigated and correlated with biochemical indices of maternal glucose tolerance at birth: glycosylated haemoglobin (HbA1), serum corrected fructosamine and the area under the oral glucose (50 g) tolerance (OGTT) curve. Growth in all physical dimensions, especially weight, showed a downward shift towards a reference mean. These changes in relative size were caused by slower growth velocities. None of the mothers had abnormally high concentrations of HbA1 or fructosamine nor an abnormal OGTT. However, weight velocities did show small but significant correlations with fructosamine (r = -0.42), and OGTT area units (r = 0.39) but not with HbA1. For some macrosomic babies born to apparently normal mothers, birth is seen to interrupt a process operating in prenatal life that accelerates growth. Covert abnormalities of maternal glucose homeostasis could explain this. Abnormal glucose tolerance during pregnancy might therefore be viewed as a continuum extending from (i) its maximum expression, the frankly diabetic state, through (ii) gestational diabetes to (iii) the mother who has no biochemically evident abnormality of glucose homeostasis but who has sufficient alteration to modify fetal growth. Post-natal growth of LFD babies is additional information which, when taken along with other markers of maternal glucose tolerance, might help to identify the mother at later perinatal risk.     

Mid-arm circumference/head circumference ratios for identification of symptomatic LGA, AGA, and SGA newborn infants

Mid-arm circumference/head circumference ratios (MAC/HC) and birth weights obtained in 73 neonates were studied to compare which of these growth measurements could more accurately predict risk of metabolic complications resulting from either acceleration or retardation of fetal growth. The MAC/HC ratio was more sensitive than birth weight in distinguishing symptomatic large for gestational age (LGA) infants who were born to diabetic mothers from other LGA infants who were asymptomatic, and symptomatic from asymptomatic small for gestational age infants. In addition, the MAC/HC ratio identified symptomatic appropriate for gestational age (AGA) infants born to diabetic mothers and AGA infants with signs and symptoms of growth retardation. The MAC/HC is more useful than birth weight in assessing newborn infants at risk for the metabolic complications associated with fetal growth disorders.     

Visual evoked potentials in term light-for-gestational-age infants and infants of diabetic mothers

The latency and amplitude of the first negative peak of visual evoked potentials (VEP) were evaluated in 52 term infants, investigated within 48 h after birth. Sixteen were light-for-gestational-age (LGA), 16 were appropriate-for-gestational-age (AGA) and 20 were infants of diabetic mothers (IDM). The VEP latency was shorter in LGA infants compared to AGA infants, and it was closely related to the birth weight deviation. The VEP latency was inversely related to gestational age and positively related to head circumference. When corrected for gestational age and head circumference, the VEP latency was not significantly different between the subgroups, nor related to the birth weight deviation, ponderal index or skinfold thickness. Thus, it could be argued that the high conduction velocity in LGA infants is due to stress maturation or alternatively due to the smaller head circumference. The VEP amplitude was higher in LGA infants when compared with AGA infants, and inversely related to the birth weight deviation. No differences were found in VEP latency or VEP amplitude between IDM and AGA infants.     

Association between serum leptin and anthropometric parameters at birth and at 15th day of life in infants born asymmetrically small for gestational age

The aim of this study was to investigate changes in skinfold measurements taken at three sites, mid-arm circumference and umbilical circumference during the first 15 days of life; and to evaluate relationships between anthropometric measurements and umbilical cord blood serum leptin levels in infants born small for gestational age (SGA) and appropriate for gestational age (AGA) infants. Of 50 newborn infants, 25 were SGA and 25 were AGA. Neonates' weight, mid-arm circumference (MAC), umbilical circumference (UC), and triceps, subscapular and periumbilical skinfold thicknesses were measured (Holtain callipers) immediately after delivery. Anthropometric parameters were measured again at 15th days of age. At birth, mean birth weight, mean skinfold thickness, MAC and UC measurements in the AGA group were significantly higher than those of the SGA group. These differences were also found on the 15th day. Birth weight correlated with all skinfold thicknesses, MAC and UC at birth. Weight at 15th day of life correlated with skinfold thicknesses, MAC and UC at 15th day of life. Cord blood leptin level was significantly lower in the SGA than in the AGA infants. This difference continued on the 15th day. When cord blood leptin level was compared with that of the 15th day, we found that leptin levels in the cord blood were significantly higher. There were significantly positive correlations between leptin levels and birth weight and skinfold thicknesses when the infants were all grouped together. When the newborns were grouped according to birth weight, there were positive correlations between cord blood serum leptin levels and these parameters in the AGA group, but no correlation in the SGA group. At the 15th day of life serum leptin levels correlated with weight, subscapular and triceps skinfold thickness in the AGA group, but only with triceps skinfold thickness in the SGA group.     

Weight to length ratio—a good parameter for determining nutritional status in preterm and full-term newborns

To identify which parameter showed the strongest correlation with neonatal body fat store, when the ratios for assessing both weight-for-length and the mid-arm circumference to head circumference (MAC/HC) were included in the analysis, body anthropometrics and skinfold thickness were measured in 250 full-term and 125 preterm infants. Among the study cases, 66.7% were appropriate for gestational age, 26.7% were small for gestational age and 6.7% were large for gestational age. Sum of the skinfold thickness measured at the midtricepital and subscapular areas correlated well with body anthropometrics, weight/length ratio, body mass index, ponderal index and mid-arm circumference to head circumference ratio. Multiple stepwise regression analysis revealed that the weight/length ratio correlated best with skinfold thickness in both full-term and preterm newborn infants. Therefore, the simple weightllength ratio might be useful for evaluation of the nutritional status of intrauterine growth, and in the prediction of metabolic complications in both full-term and preterm newborns with abnormal intrauterine growth.     

Infants of diabetic mothers: echocardiographic measurements and cord blood IGF-I and IGFBP-1

El‐Ganzoury MM, El‐Masry SA, El‐Farrash RA, Anwar M, Abd Ellatife RZ. Infants of diabetic mothers: echocardiographic measurements and cord blood IGF‐I and IGFBP‐1. Background: Cardiac malformations in infants of diabetic mothers (IDMs) are five times higher than in normal pregnancies. Insulin‐like growth factor‐I (IGF‐I) is the most important growth factor in utero and is predominantly bound by IGF binding protein‐1 (IGFBP‐1). Objective: To examine the echocardiographic findings of neonates of diabetic mothers and the relationship with cord blood IGF‐I and IGBP‐1. Subjects and methods: This study was conducted on 69 neonates born to diabetic mothers who were admitted to the neonatal intensive care unit, Ain Shams University Hospitals between August 2007 and February 2008. They were classified into three groups: 20 small for gestational age, 25 appropriate for gestational age, and 24 large for gestational age. Neonates were subjected to thorough clinical examination and echocardiographic evaluation. Maternal hemoglobin A1c (HbA1c) and cord blood IGF‐I and IGBP‐1 were assessed. Results: Thirty neonates (43.5%) had hypertrophic cardiomyopathy (HCM); all of them were infants of suboptimally controlled diabetic mothers (HbA1c ≥ 7) with positive correlation between HbA1c and interventricular septal (IVS) thickness. Impaired left ventricular contractility was recorded in 52 IDMs (75.4%). The echocardiographic and laboratory measurements showed significant difference between the three studied groups. Cardiac morphological data were negatively correlated to IGFBP‐1 and positively correlated to IGF‐I and birth weight. Conclusions: The opposing relationships between cord blood IGF‐I and IGFBP‐1 on the cardiac morphological measurements supporting their putative opposing roles in HCM seen in IDMs. Birth weight is the best predictor of hypertrophied IVS especially in infants born to suboptimally controlled diabetic mothers.     

Placental villous surface area of light-for-dates infants at term

The placental villous surface area and ratios of villous surface area to body weight, length and head circumference were determined in 40 light-for-dates infants born at term. When infants were categorised by length, head circumference and ponderal index, the short infants and infants with small heads had a mean villous surface area similar to that of their peers of normal length and head circumference. However, wasted infants, with a low ponderal index, had both an absolutely and relatively reduced mean villous surface area when compared to non-wasted infants. It is concluded that not all light-for-dates infants, but only those that are wasted at birth, have quantitative placental inadequacy.     

Troponin T and NT ProBNP Levels in Gestational,Type 1 and Type 2 Diabetic Mothers and Macrosomic Infants

This study compares NT proBNP and troponin T levels in umbilical cord arterial blood and postnatal echocardiographic findings for infants of gestational and pregestational diabetic mothers and macrosomic infants. Twenty-seven infants of pregestational diabetic mothers, 61 infants of gestational diabetic mothers and 37 macrosomic infants of nondiabetic mothers were prospectively enrolled in this study along with a control group of 58 healthy infants of mothers without any pregestational or gestational disorders as the control group. All enrollees were born after 34 weeks of gestation. For this study, umbilical cord blood was drawn during delivery to determine NT proBNP and troponin T levels. Echocardiography was performed 24–72 h after the delivery. Umbilical cord troponin T and NT proBNP levels were found to be higher in the diabetic and macrosomic groups than in the control group (all of them p < 0.001). NT proBNP levels were positively correlated with interventricular septum thickness in the pregestational and gestational infants of diabetic mothers groups (r = 0.564 and r = 0.560, respectively, p < 0.01). Both pregestational and gestational diabetic mothers were divided into two groups according to HbA1c levels in the third trimester as good (<6.1 %) and suboptimal (>6.1 %) metabolic control. In the good and suboptimal metabolic control diabetic groups, NT proBNP levels were also positively correlated with interventricular septum thickness (r = 0.536 and r = 0.576, respectively, p < 0.01). In the suboptimal metabolic control diabetic group, NT proBNP was only found to be positively correlated with the left ventricular mass index (r = 0.586, p < 0.01). While there was no correlation in the myocardial performance index between infants of diabetic mothers and the control group, the myocardial performance index of macrosomic infants was lower than that of the control group (p = 0.017). Cardiac biomarkers (NT proBNP and troponin T) were elevated in infants of diabetic mothers and macrosomic infants. While there was a positive correlation between NT proBNP levels and cardiac structure in infants of pregestational and gestational diabetic mothers, there was no relationship between NT proBNP levels and cardiac function.     

Fetal growth and parental consanguinity

Anthropometric measurements made on 322 newborn infants in South India were related to parental consanguinity. Uncle-niece and first-cousin marriages were common and the average coefficient of inbreeding was as high as 0·0329. The measurements (weight, length, head circumference, and triceps and subscapular skinfold thicknesses) of the uncle-niece groups (52 infants) were smaller than those of the first-cousin group (61 infants) which in turn were smaller than the nonconsanguineous group (196 infants). Statistical significance (P<0·01) was only recorded between the weights of the three groups (means 2650·4, 2794·1, and 2833·8 g) and between the lengths of the uncle-niece group and the nonconsanguineous group (means 46·92 and 47·79 cm). There were no social class or residential differences between the groups. We conclude that there are likely to be recessive genes present in the population, slightly retarding fetal growth.     

Posthospitalization growth and bone mineral status of normal preterm infants. Feeding with mother's milk or standard formula

The growth and bone mineralization were studied in ten preterm infants fed human milk and 14 preterm infants fed cow's milk-based formula. After discharge from the hospital, at 42, 48, and 56 weeks' postmenstrual age, anthropometric measures of weight, length, occipital frontal circumference, mid-upper arm circumference, triceps, and subscapular skin folds were obtained. Blood was drawn for determinations of serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and albumin levels. Bone mineral analyses were performed by photon absorptiometry. Mean (+/- SD) gestational ages in nursing and formula-fed infants were similar (32.0 +/- 2.5 vs 31.5 +/- 1.5 weeks), as were their mean (+/- SD) birth weights (1.76 +/- 0.42 vs 1.52 +/- 0.30 kg). After hospitalization, both groups had similar rates of growth in weight, length, head circumference, mid-upper arm circumference, triceps, and subscapular skinfold thickness. The formula-fed group had higher serum phosphorus levels at 42 weeks, higher serum calcium levels at 48 weeks, and higher serum albumin concentrations at 56 weeks than the breast-fed group. By 56 weeks' postmenstrual age, the bone mineral content was higher in the formula-fed group. Our data suggest that after hospitalization, preterm infants fed their own mother's milk have similar growth patterns but a different bone mineralization rate compared with preterm infants fed a standard cow's milk-based formula.     

Neonatal skinfold thickness. Measurement and interpretation at or near term.

Skinfold thickness was measured at five sites in 750 infants. The study population was unselected except that twin pregnancies and the infants of diabetic mothers were excluded, and very preterm infants were under represented. A pilot study had indicated that skinfold measurement was most reproducible at the thigh site. Thigh skinfold correlated better with the sum of other skinfolds than did skinfold measurement at any other site and closely resembled the summed skinfold in correlations with a number of maternal and fetal variables. Median skinfold increased with birthweight and was greater in girls than in boys. ''Corrected skinfold'', a mathematical approach to comparing skinfolds in infants of differing sex and birthweight, is suggested as an alternative to absolute skinfold measurement.     

Accuracy of anthropometric measurements in predicting symptomatic SGA and LGA neonates

Mid-arm circumference, mid-arm circumference/head circumference ratio, ponderal index and skinfold thickness at five sites (biceps, triceps, quadriceps, subscapular and flank) were measured in 91 small-for-gestational-age (SGA) and 101 large-for-gestational-age (LGA) neonates to investigate their accuracy in identifying neonates at high risk of complications resulting from disturbed intrauterine growth. Thirty-one of 91 SGA and 19 of 101 LGA neonates who developed hypoglycaemia and/or polycythaemia were regarded as symptomatic. Mean values of all of the anthropometric parameters differed significantly between symptomatic and asymptomatic SGA or LGA neonates. The quadriceps skinfold thickness was the most sensitive index in predicting symptomatic SGA and LGA neonates (sensitivity 0.93 and 0.95, respectively). The mid-arm circumference was also a very sensitive index in predicting symptomatic SGA neonates (sensitivity 0.94) but its specificity was extremely low (0.20). The rest of the parameters showed lower sensitivity than quadriceps skinfold thickness associated with similarly low specificity and validity. The findings of this study indicate that the quadriceps skinfold thickness is the most reliable index for use as a screening test for clinical evaluation of SGA and LGA neonates who are likely to develop complications as a result of disturbed intrauterine nutrition.