Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant.

The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover, we studied the leucine turnover in preterm infants soon after birth and again after 7 days. Ten infants from preeclamptic mothers (birth weight 1,280 +/- 240 g, gestational age 31 +/- 2 weeks) and 15 control patients (birth weight 1,320 +/- 210 g, gestational age 30 +/- 2 weeks) were enrolled. The leucine turnover was measured using a primed constant 5-hour intravenous infusion of [1-(13)C]leucine within the first 24 h after delivery and again on day 7 of life. The turnover (leucine flux; micromol.kg(-1).h(-1)) was calculated from the enrichment in alpha-ketoisocaproic acid in plasma. The leucine turnover on day 1 was 300 +/- 65 in the preeclampsia group and 358 +/- 70 in the controls (ANOVA, p < 0.05). The values on day 7 were 474 +/- 73 in the preeclampsia group and 485 +/- 80 in the control group (n.s.). To conclude, the leucine turnover on day 1 is lower in infants of preeclamptic mothers as compared with controls. This difference has disappeared on day 7 of life after receiving the same protein and energy intake.     

Age-dependent differences in the relationship between plasma and brain extracellular fluid concentrations of magnesium after MgSO4 infusions in miniswine.

Magnesium is a potential neuroprotective agent in the treatment of head injury and ischemia whose efficacy is likely determined by increases in brain extracellular fluid (ECF) magnesium, which in turn depends on its concentration in plasma. The objectives of this study were to: 1) examine the effects of increasing plasma magnesium concentration ([Mg]plasma) to 4-6 mM on brain ECF magnesium concentration ([Mg]ECF) and 2) determine whether maturational changes occur in the transfer of magnesium into brain ECF for newborn and more mature (approximately 1 month old) miniswine. Increases in [Mg]plasma by systemic administration of MgSO4 resulted in similar maximal elevations in brain [Mg]ECF for both age groups (193+/-76% versus 253+/-106% of control for newborn and 1-month-old miniswine, respectively). Calculations of half-lives (t1/2) for the increase and decrease in magnesium concentration (t1/2 uptake and t1/2 clearance) were used to characterize magnesium kinetics in plasma and brain ECF. Plasma magnesium uptake was shorter in 1-month-old (t1/2 = 11.1+/-0.9 min) compared with newborns (12.9+/-1.7 min, p < 0.05). The faster increase in [Mg]plasma probably contributed to a faster uptake of brain [Mg]ECF in 1-month-old compared with newborn swine (t1/2 uptake = 27.9+/-12.8 versus 46.0+/-20.9 min, respectively, p < 0.05). Although plasma magnesium clearance was shorter in 1-month-old swine compared with newborn (t1/2 = 34.3+/-7.0 versus 74.7+/-33.7 min, respectively, p < 0.05), the clearance of magnesium from the brain ECF was similar for each age group. Reductions in blood pressure and heart rate occurred during hypermagnesemia and were similar in each age group. This study shows that acute elevations in [Mg]plasma to 4-6 mM result in similar relative increases in brain [Mg]ECF for both newborn and 1-month-old miniswine. However, there are maturational differences, as demonstrated by the faster rate of magnesium uptake into the ECF observed in the older miniswine.     

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.     

Plasma creatinine in the first month of life.

The creatinine-kinetics method of analysis was used to study the changes, during the first month of life, in plasma creatinine levels in 34 newborn infants receiving no treatment with drugs. Plasma creatinine values during the first 5 days of life ranged from 188 to 17 mumol/l. After day 5 plasma levels were fairly stable throughout the first month, with a mean value of 35 +/- 2 (range 12-62) mumol/l. Twenty-two infants receiving treatment with gentamicin-ampicillin-cloxacillin were also studied. Seven of them had raised plasma creatinine concentrations after day 5, well beyond the range of concentrations found for infants receiving no drugs. Plasma creatinine, measured by the kinetic method, appears to provide a useful index of renal function in the neonatal period.     

Plasma creatinine in the first month of life

The creatinine-kinetics method of analysis was used to study the changes, during the first month of life, in plasma creatinine levels in 34 newborn infants receiving no treatment with drugs. Plasma creatinine values during the first 5 days of life ranged from 188 to 17 mumol/l. After day 5 plasma levels were fairly stable throughout the first month, with a mean value of 35 +/- 2 (range 12-62) mumol/l. Twenty-two infants receiving treatment with gentamicin-ampicillin-cloxacillin were also studied. Seven of them had raised plasma creatinine concentrations after day 5, well beyond the range of concentrations found for infants receiving no drugs. Plasma creatinine, measured by the kinetic method, appears to provide a useful index of renal function in the neonatal period.     

Kinetic modeling of plasma leucine levels during continuous venovenous extracorporeal removal therapy in neonates with maple syrup urine disease

A kinetic modeling of leucine plasma concentration changes is proposed to describe the plasma leucine reduction rate during continuous extracorporeal removal therapy (CECRT) in neonates with maple syrup urine disease. Data were obtained from seven neonates using a bicompartmental model for the best fitted curve of plasma leucine decrease during CECRT. During the first 3 h, leucine plasma levels decreased according to an exponential curve: [Leu](t) = [Leu](i) x 0.95 x 10(-0.09t) where [Leu](t) is the leucine plasma level (mumol/L) at time t (h) during CECRT and [Leu](I) is the initial plasma level. From h 4 to the end of CECRT, a second exponential curve was observed: [Leu](t) = [Leu](i) x 0.74 x 10(-0.05t). Plasma leucine levels obtained from three other neonates were similar to those predicted by the model. The apparent distribution volumes for leucine that correspond to the two exponential equations obtained were calculated from the leucine mass removal collected in the spent dialysate and ultrafiltrate. The distribution volume was 34 +/- 3% of body weight during the first 3 h of CECRT and 72 +/- 7% from h 4 to the end of CECRT. These figures are similar to known values for the extracellular water compartment and for total body water in the newborn. The findings suggest that leucine handling during CECRT is similar to that of nonprotein-bound small-molecular-weight solutes such as urea.     

Pharmacokinetic observations of phenytoin disposition in the newborn and young infant

The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks. The plasma DPH half-life during the first week of life in term infants was prolonged and very variable (20-7 +/- 11-6 h, mean +/-SD). Thereafter the plasma half-life was much shorter (7-6 +/- 3-5 h). In preterm infants the half-life was much longer (75-4 +/- 64-5 h) and more variable. The mean apparent volume of distribution was similar in these groups of infants: preterm newborn 0-80 +/- 0-22 l/kg, term infants during the first week of life 0-80 +/- 0-26 l/kg, and term infants greater than 2 weeks of age 0-73 +/- 0-18 l/kg. Predictions of steady-state plasma DPH concentrations, based on these kinetic parameters, were confirmed. Very low "trough" plasma DPH concentrations were observed after the 14th postnatal day in 19 infants receiving 8 mg/kg per 24 h orally. On the other hand, infants of less than one week of age receiving the same dose, especially if preterm, frequently showed drug accumulation to toxic plasma DPH concentrations. The impaired binding of DPH to newborn plasma protein was confirmed but "normal adult values" were approached by the age of 3 months. An intravenous loading dose of 8 mg/kg (sodium phenytoin) can be expected to generate a mean plasma DPH concentration of 10 mg/l (40 micronmol/l) in the newborn. Loading doses of up to 12 mg/kg were given without untoward effects. During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data. Beyond the second week of life, however, a dose of 8 mg/kg per 24 h is probably inadequate for most infants.     

Pharmacokinetic observations of phenytoin disposition in the newborn and young infant.

The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks. The plasma DPH half-life during the first week of life in term infants was prolonged and very variable (20-7 +/- 11-6 h, mean +/-SD). Thereafter the plasma half-life was much shorter (7-6 +/- 3-5 h). In preterm infants the half-life was much longer (75-4 +/- 64-5 h) and more variable. The mean apparent volume of distribution was similar in these groups of infants: preterm newborn 0-80 +/- 0-22 l/kg, term infants during the first week of life 0-80 +/- 0-26 l/kg, and term infants greater than 2 weeks of age 0-73 +/- 0-18 l/kg. Predictions of steady-state plasma DPH concentrations, based on these kinetic parameters, were confirmed. Very low "trough" plasma DPH concentrations were observed after the 14th postnatal day in 19 infants receiving 8 mg/kg per 24 h orally. On the other hand, infants of less than one week of age receiving the same dose, especially if preterm, frequently showed drug accumulation to toxic plasma DPH concentrations. The impaired binding of DPH to newborn plasma protein was confirmed but "normal adult values" were approached by the age of 3 months. An intravenous loading dose of 8 mg/kg (sodium phenytoin) can be expected to generate a mean plasma DPH concentration of 10 mg/l (40 micronmol/l) in the newborn. Loading doses of up to 12 mg/kg were given without untoward effects. During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data. Beyond the second week of life, however, a dose of 8 mg/kg per 24 h is probably inadequate for most infants.     

Early diagnosis of cystic fibrosis by means of sweat microosmometry

A modified sweat test procedure was studied to evaluate its practicability in the diagnosis of cystic fibrosis in newborn infants. By means of vapor pressure osmometry, we measured sweat osmolality in 131 healthy children and 63 patients with CF. Reference values were determined according to age: healthy infants 4 to 9 days of age; 121 +/- 23 mmol/kg (mean +/- SD); healthy infants 10 days to 2 months, 109 +/- 13 mmol/kg; healthy infants 2 to 12 months, 86 +/- 13 mmol/kg; and healthy children and adults 2 to 23 years, 105 +/- 14 mmol/kg. The mean of corresponding values for the 63 patients with CF was 267 +/- 34 mmol/kg. There was no overlap of values in any age group, even when the 2 SD limit was taken into account. Thus the diagnosis of CF can be made by means of this approach in newborn infants 8 days of age or older.     

Evaluation of yogurt effect on acute diarrhea in 6-24-month-old hospitalized infants

Yogurt helps in treatment and prevention of diarrhea. The aim of this study was to determine the efficacy of consumption of local factory yogurt, which is made with pasteurized milk, on moderately dehydrated hospitalized infants aged 6-24 months with acute non-bloody and non-mucoid diarrhea. Eighty moderately dehydrated breast-feeding children aged between 6-24 months with acute non-bloody and non-mucoid diarrhea for fewer than four days were included in the study. Patients were randomly separated into two groups according to their treatment. Infants in the case group received at least 15 ml/kg/day of pasteurized cow milk yogurt orally plus routine hospital treatment. Infants in the control group received routine hospital treatment as in the case group. Weight gains, period of hospitalization, and reduction in diarrhea frequency during hospitalization period of the two groups were compared. Mean duration of hospitalization (days), weight gain, and reduction in diarrhea frequency were 2.7 +/- 0.91 vs 3.1 +/- 0.74 days, 435 +/- 89.20 vs 383 +/- 98.9 g, and 4.30 +/- 1.74 vs 3.60 +/- 1.23 times for case and control groups, respectively. Significant differences were observed in mean hospitalization days (p=0.035), reduction in diarrhea frequency (p=0.049) and weight gain (p=0.017). This study recommends universal use of yogurt in acute non-bloody diarrhea.     

Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group

OBJECTIVE: To determine the safety, tolerance, pharmacokinetics and efficacy of linezolid, a new oxazolidinone antibiotic in the treatment of community-acquired pneumonia in hospitalized children. DESIGN: A Phase II, open label multicenter study of intravenous linezolid followed by oral linezolid suspension, both at a dose of 10 mg/kg every 12 h. Efficacy was assessed at 7 to 14 days after the last dose of linezolid. PATIENTS: Children 12 months to 17 years old with community-acquired pneumonia admitted to the hospital of 14 participating centers. RESULTS: From July 21, 1998, through May 14, 1999, 79 children were enrolled and 78 received linezolid. Sixty-six children completed treatment and follow-up and were evaluable for clinical outcome. The median age of the evaluable patients was 3 years (range, 1 to 12 years); 47 were 2 to 6 years old. Pathogens were isolated from blood or pleural fluid cultures in 8 children: Streptococcus pneumoniae, 6 (2 penicillin-resistant); Group A Streptococcus, 1; methicillin-resistant Staphylococcus aureus, 1. Chest tubes were placed in 9 patients. The mean total duration of intravenous and oral administration was 12.2 +/- 6.2 days (range, 6 to 41 days). The mean peak and trough plasma concentrations of linezolid were 9.5 +/- 4.8 and 0.8 +/- 1.2 microg/ml, respectively. At the follow-up visit 7 to 14 days after the last dose of linezolid, 61 patients (92.4%) were considered cured including all the patients with proven pneumococcal pneumonia, one failed (methicillin-resistant Staphylococcus aureus) and 4 were considered indeterminate. The most common adverse effects in the intent to treat group were diarrhea (10.3%), neutropenia (6.4%) and elevation in alanine aminotransferase (6.4%). CONCLUSIONS: Linezolid was well-tolerated and could be considered an alternative to vancomycin for treating serious infections caused by antibiotic-resistant Gram-positive cocci in children pending results of additional studies.     

Pharmacokinetics of intravenous clindamycin in newborn infants

We studied 12 newborn infants (gestational ages 26-39 wk [mean +/- SD, 30.6 +/- 4.7]; birth weight 640-2700 g, [mean, 1,322 +/- 688]; postnatal age 1-24 days [mean, 9.6 +/- 8.5]) who received clindamycin phosphate for suspected or proven necrotizing enterocolitis (ten patients) or suspected anaerobic septicemia (two patients) in doses of 3.2-11 mg/kg every six hours. Range of mean serum concentration of clindamycin at steady state was between 12.7 and 40 micrograms/ml (therapeutic range = 2-10 micrograms/ml). High concentrations could be attributed to elimination T1/2 (6.3 +/- 2.1 hr) 100% longer than in older children or adults. Clindamycin clearance (61.6 +/- 31.6 hr ml/kg/hr) was lower than in older children or adults. Because of the observed prolongation in T1/2 and correspondingly lower clearance, the IV dose of clindamycin in newborn infants should be reduced to 15-20 mg/kg/day given in four daily doses.     

Evaluation of plasma ionized magnesium levels in neonatal hyperbilirubinemia

Plasma levels of ionized magnesium (IMg) measured by ion-selective electrode were investigated in neonatal hyperbilirubinemia by comparing the newborns with (> or =205 microM) and without (<205 microM) significant hyperbilirubinemia (groups of severe and moderate hyperbilirubinemia, respectively). Serum bilirubin, plasma IMg, and ionized calcium (ICa) levels were determined in 165 healthy term newborns with nonhemolytic indirect hyperbilirubinemia during the first 10 d of life. Mean serum bilirubin, plasma IMg, and ICa levels were 200.1 +/- 126.5 microM, 0.54 +/- 0.12 mM, and 1.15 +/- 0.12 mM, respectively, in 165 newborns whose mean postnatal age was 156.1 +/- 46.5 h, and there was a significant positive correlation between the mean serum bilirubin and plasma IMg levels (r = 0.535, p < 0.001). Serum bilirubin levels (304.4 +/- 83.8 microM versus 94.1 +/- 54.7 microM) and plasma IMg levels (0.6 +/- 0.12 mM versus 0.49 +/- 0.1 mM) were significantly higher and plasma ICa levels (1.13 +/- 0.12 mM versus 1.18 +/- 0.12 mM) were significantly lower in the group of severe hyperbilirubinemia (n = 83) when compared with the group with moderate hyperbilirubinemia (n = 82). Seventeen of the 83 cases of severe hyperbilirubinemia had IMg levels above the normal range (> or =0.69 mM), whereas none of the 82 cases of moderate hyperbilirubinemia had elevated IMg levels. Fifteen of the 17 with high IMg levels had bilirubin levels >290 microM. Results of the present study suggest that increase in plasma IMg may be due to extracellular movement of Mg, a principally intracellular ion, resulting from generalized cellular injury including neurons and erythrocytes. Considering neuroprotective functions and beneficial effects of Mg ion in improving neurologic outcome, we also may speculate the possibility of a neuroprotective role or a compensatory mechanism in IMg increase against emerging toxicity risk of increasing serum bilirubin levels.     

Early treatment of acute stress disorder in children with major burn injury.

OBJECTIVE: This study examines retrospectively the response rate of pediatric burn survivors with acute stress disorder to either imipramine or fluoxetine. METHODS: On retrospective chart review, 128 intensive care unit patients (85 boys, 43 girls) with 52%+/- 20% total body surface area burn, length of stay of 32.8+/- 25.2 days, mean age of 9.1+/- 4.7 yrs, and age range of 13 months to 19 yrs met criteria for acute stress disorder after >or=2 days of symptoms and were treated with either imipramine or fluoxetine. If significant improvement did not occur within 7 days, the medication was either increased or switched to the other class. RESULTS: Initially, 104 patients were treated with imipramine and 24 with fluoxetine. A total of 84 patients responded to imipramine: seven of these patients required a higher dose. A total of 18 patients responded to initial fluoxetine treatment. Of 26 nonresponders to the initial medication, 13 imipramine failures and one fluoxetine failure refused further treatment. The other 12 responded to the second medication. Therefore, 114 of 128 treated patients (89%) responded to either fluoxetine (mean dose, 0.30+/- 0.14 mg/kg) or imipramine (mean dose, 1.30+/- 0.55 mg/kg). Response was independent of sex and age but was less for those with burns of >60% total body surface area. The side effects of each medication were not significant. Most patients continued treatment for >or=3 months; some required 6 months of treatment before successful discontinuation. CONCLUSIONS: Early treatment of acute stress disorder with either imipramine or fluoxetine is often able to reduce its symptoms. This is a review of a single hospital's experience in managing psychiatric distress in this very high-risk group of burned children. Additional clinical studies are needed before generalizing these findings.     

Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion

Tolerance to opioid-induced sedation has been reported in neonates sedated with fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation. We undertook a prospective analysis of eight newborn infants sedated with fentanyl during extracorporeal membrane oxygenation therapy for respiratory failure. We recorded daily mean fentanyl infusion rate, measured serial plasma fentanyl concentrations, and documented the occurrence of spontaneous motor activity or respiratory effort. Mean fentanyl infusion rate increased steadily during the period of infusion from a mean of 9.2 +/- 1.9 (SEM) micrograms/kg per hour on day 1 to a mean of 21.9 +/- 4.5 micrograms/kg per hour by day 6. Mean plasma fentanyl concentrations increased steadily during the period of fentanyl infusion from 3.1 +/- 1.1 (SEM) ng/ml on day 1 to 13.9 +/- 3.2 ng/ml on day 6. All infants exhibited movement in response to gentle tactile stimulation throughout the period of infusion, and seven of eight infants manifested spontaneous movement of the extremities and eye opening. Our results indicate that when fentanyl is used for sedation in neonates, the plasma concentrations required for satisfactory sedation steadily escalate, possibly indicating the rapid development of tolerance to the sedating effects of fentanyl.     

Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition

A mixture of amino acids designed to maintain normal plasma amino acid concentrations of infants and children requiring parenteral nutrition was evaluated in 40 infants and children receiving only parenteral nutrients (2.39 +/- 0.26 g/kg/d of amino acids and 110.3 +/- 10.4 kcal/kg/d) for five to 21 days. The children ranged in weight from 2.0 to 12.6 kg (median weight, 3.83 kg; fifth to 95th percentile, 2.06 to 11.1 kg) and in age from 1 week to 43.6 months (median age, 2.7 months; fifth to 95th percentile, 0.2 to 25.3 months). Mean weight gain was 11.0 +/- 5.0 g/kg/d; mean nitrogen balance was 242 +/- 70 mg/kg/d. Plasma concentrations of all amino acids except tyrosine were within the normal range (ie, within the 95% confidence limits of the two-hour postprandial plasma concentrations observed in 30-day-old, healthy, normally growing, breast-fed, term infants) throughout the period of study. Mean prestudy and poststudy serum total protein, albumin, and transthyretin (prealbumin) concentrations were not significantly different. However, plasma transthyretin concentration increased in all children with low prestudy concentrations. Mean poststudy serum total bilirubin concentration of the total population was not different from the mean prestudy concentration. This was true also for the 31 children who received the parenteral amino acid mixture for more than ten days. In contrast to the expected 30% to 50% incidence of cholestasis, only one of these 31 experienced an unexplained increase in serum total bilirubin concentration during study, suggesting that normalizing plasma amino acid concentrations and/or providing taurine during parenteral nutrition may decrease the incidence of cholestasis associated with this therapy.     

Nocturnal acid breakthrough in children with reflux esophagitis taking proton pump inhibitors

OBJECTIVES: We aimed to determine if nocturnal acid breakthrough occurs in children receiving proton pump inhibitors for reflux esophagitis, and to compare the healing of esophagitis in children with nocturnal acid breakthrough receiving proton pump inhibitors +/- ranitidine. METHODS: This is a prospective, double-blind study. Endoscopic and histologic esophagitis were scored 0-4 and 0-3, respectively. Patients were treated with a proton pump inhibitor twice daily and esophagogastric pH monitoring was performed at week 3. Patients with nocturnal acid breakthrough were randomized. One group received ranitidine and the other received placebo at bedtime in addition to proton pump inhibitor therapy. Endoscopy was performed on all patients (with pH monitoring on patients with nocturnal acid breakthrough) during the 17th week of therapy. RESULTS: We enrolled 18 patients, ages 1 to 13 years (mean = 10.3 years). Mean baseline endoscopic and histologic scores were 3.1 +/- 1.4 and 1.8 +/- 0.7, respectively. Mean dose of proton pump inhibitor was 1.3 mg/kg +/- 0.6. Nocturnal acid breakthrough was documented in 16/18 (89%) patients. Seven patients received ranitidine and 9 received placebo. The reflux index improved: mean of 14.3 at baseline, 2.0 at week 3 (P = 0.0001), and 5.1 at week 17 (P = 0.09). Nocturnal acid breakthrough persisted in 9/12 (75%) patients, 3 of whom received ranitidine at bedtime. Esophagitis improved in all patients following therapy: mean endoscopy and histology scores were 1.6 +/- 1.8 (P = 0.0020) and 0.8 +/- 0.9 (P = 0.0013), respectively. Symptoms significantly improved from a mean score of 2.0 at baseline to 0.4 at week 17 (P = 0.0001). CONCLUSIONS: Nocturnal acid breakthrough is common in pediatric patients treated with proton pump inhibitors. Reflux index remains normal in spite of nocturnal acid breakthrough. Symptoms and esophagitis continued to improve during therapy in spite of nocturnal acid breakthrough. There appears to be no additional benefit to supplementation with ranitidine at bedtime.     

Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism

OBJECTIVES: To test whether early treatment with a high initial dose of levothyroxine can prevent suboptimal mental development in all neonates with congenital hypothyroidism (CH). STUDY DESIGN: Sixty-one patients, 27 with severe CH and 34 with mild CH, were treated either early (<13 days) or late (> or =13 days) with either a high initial dose of levothyroxine (> or =9.5 microg/kg/d) or a low initial dose (<9.5 microg/kg/d). With these criteria, 4 treatment groups were formed. The results of the Bayley test, performed at the age of 10 to 30 months and expressed as mental developmental index (MDI) and psychomotor developmental index (PDI), were related to socioeconomic status, treatment group, initial free thyroxine (FT(4)) concentration, and mean FT(4) concentration during the first 3 months of treatment (FT(4)-A) and the ensuing 9 months (FT(4)-B). RESULTS: Mean (+/- SD) MDI was 113 +/- 14, and mean PDI was 114 +/- 12. In the severe CH group, only the patients treated early with a high initial dose had normal MDI scores (124 +/- 16), whereas the scores of the other groups ranged from 97 to 103. In contrast, all patients in the mild CH group had normal scores (range, 122-125), except those in the group treated late with a low initial dose, whose score was 110 +/- 10. Forty-three percent of the variance in MDI and PDI scores was explained by treatment factors, such as the treatment group, initial FT(4) concentration, FT(4)-A, and FT(4)-B. CONCLUSIONS: Our data suggest that optimal treatment includes achievement of euthyroidism before the third week of life by initiation of therapy before 13 days with a levothyroxine dose above 9.5 microg/kg/d and maintenance of FT(4) concentrations in the upper normal range during the first year. Thus treated, patients with CH can achieve normal psychomotor development at 10 to 30 months, irrespective of the severity of the disease.     

Vitamin K status of lactating mothers, human milk, and breast-feeding infants

Hemorrhagic disease of the newborn is a disease of breast-feeding newborns. There is little information on longitudinal breast milk concentrations of phylloquinone (vitamin K1) or the effects of maternal phylloquinone supplements on breast milk. In study part 1, 11 lactating mothers, who received 20 mg of phylloquinone orally, had rises in plasma (less than 1 to 64.2 +/- 31.5 ng/mL by 6 hours) and breast milk concentrations (from 1.11 +/- 0.82 to 130 +/- 188 ng/mL by 12 hours). In part 2, 23 lactating mothers and their infants were observed longitudinally along with a formula-fed control group of infants (n = 11). Mean breast milk concentrations of phylloquinone at 1, 6, 12, and 26 weeks were 0.64 +/- 0.43, 0.86 +/- 0.52, 1.14 +/- 0.72, and 0.87 +/- 0.50 ng/mL, respectively, in the infants fed human milk. Maternal phylloquinone intakes (72-hour dietary recalls) exceeded the recommended daily allowance of 1 microgram/kg per day. Infant phylloquinone intakes did not achieve the recommended daily allowance of 1 microgram/kg per day in any infant. Plasma phylloquinone concentrations in the infants fed human milk remained extremely low (mean less than 0.25 ng/mL) throughout the first 6 months of life compared with the formula-fed infants (4.39 to 5.99 ng/mL). In this small sample, no infant demonstrated overt vitamin K deficiency. Despite very low plasma phylloquinone concentrations, vitamin K supplements (other than in the immediate newborn period) cannot be recommended for exclusively breast-fed infants based on these data.     

A randomized study of the efficacy of sensory-motor-oral stimulation and non-nutritive sucking in very low birthweight infant

To assess if sensory-motor-oral stimulation and non-nutritive sucking gavage feeding enhances the oral feeding performance of preterm infants born between 26 and 32 weeks of gestational age. STUDY DESIGN: Very low birthweight infants (n=98) were randomized into a experimental and control group. Preterm infants in the experimental group received sensory-motor-oral stimulation and non-nutritive sucking and infants in the control group received a sham stimulation program. Both were administered from when they reached enteral diet (100 kcal/kg/day) until the beginning of oral diet. Primary outcome was length of hospital stay. RESULTS: Independent oral feeding was attained significantly earlier in the experimental group than the control group, 38+/-16 days of life (mean+/-S.D.) versus 47+/-17 days of life, respectively (P<0.001) There was significant difference in length of hospital stay between the two groups (41.9+/-17 (mean+/-S.D.) versus 52.3+/-19 days (P<0.01)). CONCLUSION: Sensory-motor-oral stimulation, together with early non-nutritive sucking (as soon as the newborn reaches full diet and is clinically stable) in very low birthweight preterm infants, as long as they are clinically stable, in this study, earlier initiation of oral feeding and earlier hospital discharge.