Marla M. Mills

Abnormal iron distribution in infants of diabetic mothers: Spectrum and maternal antecedents

Because chronic hypoxemia causes a redistribution of iron from serum and storage pools into an expanding erythrocyte mass, and because infants of diabetic mothers are often hypoxemic in utero and have a high prevalence of polycythemia at birth, we studied iron distribution in 43 term infants of diabetic mothers. Twenty-four infants were at an appropriate size for gestational age; 19 were large for gestational age. At birth, 28 infants (65%) had abnormal serum iron profiles; eight had decreased ferritin concentrations only (stage 1), nine had decreased ferritin and increased total iron-binding capacity values (stage 2), and 11 had these serum findings plus elevated free erythrocyte protoporphyrin concentrations (stage 3). The hypoglycemic infants who were large for gestational age (n = 14) had a higher prevalence of abnormal iron profiles than euglycemic infants who were appropriate in size for gestational age (n = 20; 93% vs 50%; p = 0.009). Progressively abnormal iron profiles were associated with higher glycosylated fetal hemoglobin values, greater degrees of macrosomia, increased hemoglobin and erythropoietin concentrations, and increased erythrocyte/storage iron ratios. Erythropoietin concentrations were inversely linearly correlated with serum iron values (n = 32, r = -0.54; p = 0.003). The combined erythrocyte and storage iron pools were significantly lower in infants with abnormal iron values whose mothers were diabetic, particularly in infants of women with confirmed diabetic vasculopathy. We speculate that these findings are likely due to (1) increased fetal iron utilization during compensatory hemoglobin synthesis in response to chronic hypoxemia and (2) reduced iron transfer during late gestation complicated by diabetes.

Effect of postnatal steroid administration on serum vitamin A concentrations in newborn infants with respiratory compromise

Antenatal administration of glucocorticoids accelerates the fetal maturation of the lung, liver, and gastrointestinal tract. ~-3 w e previously demonstrated a significant elevation of.serum retinol, retinol-binding protein, and transthyretin concentrations in the cord blood of newborn infants whose mothers received betamethasone antenatally. 4 It was unclear from that study, however, whether this represented an effect primarily on the mother, the placenta, or the fetus. Mammel et al. 5 and others 6 demonstrated that postnatal steroid administration decreases alveolar-arterial oxygen gradients and improves lung mechanics in bronchopulmonary dysplasia, The mechanism of action remains unknown. Vitamin A has also been implicated in the prevention and treatment of bronchopulmonary dysplasia by promoting normal lung development and healing. 78 On the basis of these studies, we investigated the effect of postnatal dexamethasone administration on the vitamin A status of 13 infants who were treated with steroids because of significant respiratory compromise.

Reduced neonatal liver iron concentrations after uteroplacental insufficiency

Neonatal liver (storage) but not heart (nonstorage) tissue iron concentrations were reduced by 60% at autopsy in 15 newborn infants who had gestations complicated by uteroplacental insufficiency because of maternal hypertension or Potter syndrome. The hepatic iron reductions in term and preterm infants, and with either antecedent condition, were similar.

Metabolic response of preterm infants to variable degrees of respiratory illness

In older children and adults, physiologic instability associated with severe illness causes increased cellular oxygen consumption (VO2), increased serum lactate and cortisol levels, and more negative nitrogen balance. To determine the metabolic response of preterm infants to severity of respiratory illness, we analyzed VO2, nitrogen balance, urinary 3-methyl-histidine and norepinephrine concentrations, and serum levels of lactate and cortisol as a function of ventilatory index (VI). Twelve 2-day-old premature infants who were appropriate in size for gestational age (mean +/- SEM birth weight: 1460 +/- 251 gm) and who required mechanical ventilation for respiratory distress syndrome had VO2 and carbon dioxide production measured by indirect calorimetry and blood and urine samples obtained concurrently. All infants received amino acids, 1.0 gm/kg per day, and a mean energy intake of 27 +/- 3 kcal/kg per day, provided as a parenteral dextrose solution. The resting energy expenditure exceeded energy intake in all infants. The VO2 value ranged from 5.5 to 9.2 ml/kg per minute and was directly correlated with VI (r = 0.79; p = 0.002). Nitrogen balance ranged from -160 to 53 mg/kg per day (mean: -33 +/- 21 mg/kg per day) but was not dependent on VI (r = 0.04) or VO2 (r = 0.01). The serum lactate level correlated directly with VI (r = 0.82; p = 0.002) and VO2 (r = 0.60; p = 0.05), but cortisol and urinary norepinephrine levels did not. We conclude that preterm infants with respiratory distress syndrome have increased VO2 rates and serum lactate concentrations directly related to the degree of respiratory illness. They are generally in a state of mildly negative nitrogen balance, the degree of which is not related to severity of illness. Although these infants may require increased energy delivery during illness, they do not appear to require excessive amounts of amino acids.

Rate of change of blood pressure in premature and full term infants from birth to 4 months

Systolic and diastolic blood pressures were evaluated in a cohort of 61 non-hypertensive premature [very low birth weight (VLBW),n=16; low birth weight (LBW),n=22] and full-term [normal birth weight (NBW),n=23] newborn infants admitted to a neonatal intensive care unit (NICU) and followed to their 4-month age-adjusted outpatient examination. All were receiving routine postnatal care by 7 days of age. Blood pressure was measured at 7 days of age, at discharge from the NICU, and at the outpatient examination. Simple linear regression of blood pressure on weight was used to fit a straight line to the three measurements for each infant and the average regression line for each birth weight group was then obtained. There was a significant correlation between systolic blood pressure and both weight and length at each of the measurement points and also between the change in systolic, blood pressure and change in weight from the discharge to the 4-month examination. Diastolic blood pressure tended to follow this same pattern. Gestational age was correlated significantly with the 7-day blood pressure, but postnatal age at the outpatient examination was not correlated with either systolic or diastolic blood pressure. The average slopes of systolic and diastolic blood pressure on weight (mmHg/kg body weight) were virtually identical for the LBW and NBW groups; in constrast, the average slope of the VLBW group was greater than the other two groups, and the difference was statistically significant for diastolic blood pressure. These results show significant group differences in mean blood pressure prior to 4 months of age between VLBW, LBW, and NBW groups and, for the VLBW infants, a steeper slope of the estimated regression line of blood pressure on weight between birth and 4 months.

Validation of two scoring systems which assess the degree of physiologic instability in critically ill newborn infants.

Modifications of the Physiologic Stability Index (PSI) and Therapeutic Intervention Scoring System (TISS) were used to evaluate the physiologic stability and need for therapeutic intervention in 55 infants hospitalized in the newborn ICU. After modifying the PSI to reflect neonatal physiology, we found that PSI scores correlated significantly with TISS values (r = .75, p less than .001) and Nursing Utilization Management Intervention System (NUMIS) classifications (r = .62, p less than .001). TISS values also correlated with NUMIS scores (r = .72, p less than .001). PSI and TISS scores increased significantly with each increase in NUMIS classification (p less than .001 for all comparisons). PSI and TISS scores decreased significantly between admission and either discharge (n = 41) or day 14 of hospitalization (n = 14, p less than .001). PSI and TISS scores were greater on days 1 and 5 in infants with hyaline membrane disease when compared with infants with transient tachypnea (p less than .001). Infants with PSI scores greater than or equal to 4 and TISS scores greater than or equal to 7 on day 1 took significantly longer to achieve adequate protein-calorie intakes than infants with lower first-day scores (p less than .002). The modified PSI and the TISS scoring systems are both useful objective measurements of the degree of physiologic instability in newborn infants requiring intensive care, and both scores identify those at increased risk for nutritional morbidity.

Catch-up growth, muscle and fat accretion, and body proportionality of infants one year after newborn intensive care

We studied catch-up growth, muscle and fat accretion, and body proportionality at 4 and 12 months of age corrected for prematurity in 30 very low birth weight (VLBW) (less than 1500 gm), 30 low birth weight (LBW) (1500 to 2499 gm) and 30 normal birth weight (greater than or equal to 2500 gm) infants who required newborn intensive care. At 4 and 12 months, the VLBW infants had significantly lower mean weight and length (p less than 0.01), but not lower occipitofrontal circumference percentiles, than the LBW and normal birth weight groups, and showed no catch-up weight or length growth between 4 and 12 months. All three groups had significant increases in mean upper mid-arm circumferences, mid-arm muscle circumferences, and arm muscle areas between 4 and 12 months. Mean mid-arm muscle circumferences and arm muscle areas were similar among the three groups at 4 months but became significantly stratified by birth weight groups by 12 months, with VLBW infants having the lowest mean value. In contrast, analysis of fat stores by triceps skin-fold thickness and arm fat area demonstrated no significant increases in any group between 4 and 12 months, except for arm fat area in the LBW group. The VLBW infants had significantly less fat than normal birth weight infants at 4 and 12 months. All three groups had proportional growth at both visits, as assessed by mid-arm circumference/head circumference ratio and weight-length percentile for age. The VLBW infants were significantly lighter for their length than normal birth weight infants. We conclude that VLBW infants have no first-year catch-up growth, remaining smaller than higher birth weight infants, although appropriately proportional. Somatic growth during the first year is due more to muscle than to fat accretion, especially in VLBW infants.

The Effect of Prolonged Intrauterine Hyperinsulinemia on Iron Utilization in Fetal Sheep

ABSTRACT: Newborn infants of poorly controlled insulin-dependent diabetic mothers demonstrate a redistribution of iron from serum and tissue stores into red blood cells. These changes may be due to increases in iron utilization during augmented Hb synthesis, which compensates for chronic intrauterine hypoxemia induced by prolonged fetal hyperinsulinemia. We tested this hypothesis by measuring plasma iron, total iron-binding capacity, percent iron-binding capacity saturation (total iron-binding capacity saturation), Hb concentration, total red cell Hb, and total red cell iron in the arterial blood of 11 chronically instrumented fetal sheep after 7-12 d of infusion with 15 U/day of insulin (n = 5) or placebo (n = 6). The insulin-infused fetal sheep had higher mean ± SD plasma insulin concentrations (448 ± 507 versus 11 ± 8 mU/L; p < 0.001) and lower arterial oxygen saturations (38 ± 7 versus 54 ± 9%;p < 0.02). The insulin-infused group had a lower mean plasma iron concentration (20.8 ± 10.9 versus 42.1 ± 14.7 nM/L;p < 0.02) and total iron-binding capacity saturation (36 ± 20 versus 64 ± 22%; p < 0.02) and a higher total red cell Hb (45.4 ± 8.7 versus 32.6 ± 8.8 g; p < 0.02) and total red cell iron content (154 ± 29 versus 111 ± 29 mg; p < 0.02) when compared with the placebo group. Seven to 12 d of intrauterine hyperinsulinemia decreases serum iron and increases total red cell iron, most likely by stimulating increased Hb synthesis in response to low arterial oxygen saturation. Hyperinsulemia may play a major role in the altered iron metabolism in newborn infants of diabetic mothers.

The relationship between decreased iron stores, serum iron and neonatal hypoglycemia in large-for-date newborn infants

ABSTRACT. We assessed the relationship between neonatal hypoglycemia and newborn iron status in 15 hypoglycemic, large‐for‐date newborn infants, 12 of whom were infants of diabetic mothers. These infants had significantly lower mean serum iron concentrations, ferritin concentrations, percent iron‐binding saturation and calculated iron stores, and significantly higher mean transferrin concentrations, total iron‐binding capacity concentrations and mid‐arm circumference: head circumference ratios when compared with either 15 euglycemic large‐for‐date or 15 euglycemic appropriate‐for‐date control infants (p < 0.001 for all comparisons). All hypoglycemic infants had ferritin concentrations below the 5th percentile as compared to 3 % of controls (p < 0.001), and 67 % had transferrin concentrations above the 95th percentile (controls: 0 %; p < 0.001). Only the hypoglycemic infants demonstrated a significant negative linear correlation between ferritin and transferrin concentrations (r=−0.83; p < 0.001). Decreased serum iron concentrations were associated with size at birth (r=−0.60; p= 0.01) and with increased red cell iron (r=−0.60; p= 0.01), implying a redistribution of iron dependent on the degree of fetal hyperglycemia and hyperinsulinemia. Infants with increased red cell iron had more profound neonatal hypoglycemia. These results show a significant association between decreased iron stores and neonatal hypoglycemia in macrosomic newborn infants associated with a significant shift of iron into red blood cells.

Neonatal predictors of school-based services used by NICU graduates at school age.

Background Ill or premature newborns are at increased risk for ongoing morbidity throughout childhood. Federal legislation now mandates that states provide early intervention, special education, and disability accommodations for children with special needs. Because all children born prematurely do not require all services, targeting services to the children with greatest risk is essential. This study examined whether neonatal characteristics could predict special school-based service use (speech, occupational, physical therapy, special education) in later childhood. Methods Subjects were 53 children, ages 7 to 11 years, graduates of one Midwest Level 3 neonatal intensive care unit (NICU). Neonatal data were used to calculate Neurobiologic Risk Scores (NBRS), a sum of illness factors related to brain damage. Birth weight, length of NICU stay, and NBRS were compared to the children’s school performance on standardized tools and to report cards. Results Most children studied were not receiving special school services. The NBRS and parent report of child competency were related (p = 0.01). Length of NICU stay correlated with teachers’ reports of children’s academic performance (p = 0.04), and to use of special school services use (p = 0.03). As the NBRS score increased, report card performance decreased. Conclusions Neonatal characteristics predicted school-age service use. This is important for nurses because predicting which children are most likely to need special services can aid in tracking children at high risk for prompt assessments and referrals. Parents, healthcare providers, educators, advocacy groups, and funding agencies need accurate outcome data to influence health, educational, and social policy decisions.