Use of a test diet in screening for neuroblastoma reduces false-positives attributable to food intake

We attempted to reduce false-positives during screening for neuroblastoma using a qualitative urine test by introducing a test diet without foodstuffs known to cause false-positive results. In preliminary in-vivo experiments, intake of contra-indicated foods such as orange juice or banana was shown to result in high percentages of false-positive results several hours after food intake. False-positive results were obtained even after 24 hours among breast-fed infants whose mothers received orange juice. In a controlled field trial the false-positive rate was reduced to 2.84% among 540 infants taking the test diet compared with 5.05% among 9,844 control infants following conventional guidance on contra-indicated foods (p less than 0.05). For comparison, a questionnaire survey of nationwide screening in Japan in 1987 revealed that 66% of the screening centres employed qualitative urine tests, either a Spot or Dip method. False-positive rates, including those due to inappropriate urine collection, ranged from 0.4% to 33.7% (mean 7.1%). Rates ranged from 0.2% to 18.7% (mean 3.4%) in the remaining 34% of screening centres employing a quantitative method with high performance liquid chromatography.     

Neonatal screening for biotinidase deficiency: results of a 1-year pilot study

We screened 81,243 infants born in Virginia during the 1-year period beginning Jan. 24, 1984, for deficiency of the enzyme biotinidase. A simple colorimetric screening procedure was used to detect the presence or absence of biotinidase activity on the same blood-soaked filter paper cards that are currently used in most neonatal metabolic screening programs. Two newborn infants with biotinidase deficiency were identified during the 12-month pilot study. In addition, two affected siblings of one of the newborn infants were detected through secondary family screening. On the basis of these results, the disorder appears to be at least as frequent as several others for which newborn screening is currently conducted. There were no known false-negative test results, and only 0.09% false-positive results that necessitated requests for second blood samples. False-positive test results can be readily identified by the use of a quantitative assay, which can also be used to confirm the diagnosis and to detect heterozygous family members in the case of true positives. On the basis of currently recognized criteria, biotinidase deficiency should be considered for inclusion among the metabolic disorders for which screening is performed in the neonatal period.     

Need for quantitative assessment of transglutaminase autoantibodies for celiac disease in screening-identified children

OBJECTIVES: To assess several transglutaminase autoantibody (TGAA) assays in their ability to distinguish celiac disease (CD) in screening-identified children with abnormal intestine biopsy specimens from those with normal biopsy specimens. STUDY DESIGN: Children at risk for CD (n = 54) composed of type 1 diabetics, first-degree relatives of type 1 diabetics or CD, and HLA-DQ2+ individuals followed from birth received intestine biopsy. Sera obtained at the time of biopsy were tested for TGAA, using the radioimmunoassay and 5 other commercially available enzyme-linked immunosorbent assays. RESULTS: False-positive rates ranged from 28% to 80%. The positive predictive value (PPV) of the tests ranged from 63% to 84% (lower than reported for symptomatic children). Setting a higher cutoff for each assay maximized PPV. CONCLUSIONS: There are significant quantitative differences among all TGAA assays that could affect interpretation of a positive test for CD. The overall false-positive rate for all assays was high in this population. Using the assay as a quantitative rather than qualitative tool by increasing the cutoff of positivity to indicate biopsy increases PPV. Multicenter workshops are needed to identify critical differences and to standardize TGAA assays among laboratories.     

Evaluation of the EZ-SCREEN enzyme immunoassay test for detection of cocaine and marijuana metabolites in urine specimens

The EZ-SCREEN Cannabinoid/Cocaine test is a qualitative enzyme immunoassay card test for the detection of cannabinoid and cocaine metabolites in urine specimens. Results are available in about three minutes. The test kit costs approximately $12.00 per two-drug test, and there are no additional expenses for analytical equipment. We compared the results of the EZ-SCREEN test with results of specimens analyzed by gas chromatography/mass spectrometry (GC/MS) for 36 clinical specimens positive for cannabinoids (marijuana), 38 clinical specimens positive for benzoylecgonine (cocaine), and 33 drug-free specimens. Results from our study for marijuana included: sensitivity = 92%; specificity = 89%; and efficiency = 95, 67, and 87%, respectively. In the present study, there were five false-positive tests for cocaine and one false-positive test for cannabinoids. As with all screening test results, confirmation of positive specimens by a more specific quantitative analytical method such as GC/MS is recommended.     

Iodine status of breastfed infants and their mothers' breast milk iodine concentration

Iodine is an essential nutrient for growth and development during infancy. Data on iodine status of exclusively (EBF) and partially breastfed (PBF) infants as well as breast milk iodine concentration (BMIC) are scarce. We aimed to assess (a) infant iodine nutrition at the age of 5.5 months by measuring urinary iodine concentration (UIC) in EBF (n = 32) and PBF (n = 28) infants and (b) mothers' breast milk iodine concentration (n = 57). Sixty mother–infant pairs from three primary health care centres in Reykjavik and vicinities provided urine and breast milk samples for iodine analysis and information on mothers' habitual diet. The mother–infant pairs were participants of the IceAge2 study, which focuses on factors contributing to infant growth and development, including body composition and breast‐milk energy content. The median (25th–75th percentiles) UIC was 152 (79–239) μg/L, with no significant difference between EBF and PBF infants. The estimated median iodine intake ranged from 52 to 86 μg/day, based on urinary data (assuming an average urine volume of 300–500 ml/day and UIC from the present study). The median (25th–75th percentiles) BMIC was 84 (48–114) μg/L. It is difficult to conclude whether iodine status is adequate in the present study, as no ranges for median UIC reflecting optimal iodine nutrition exist for infants. However, the results add important information to the relatively sparse literature on UIC, BMIC, and iodine intake of breastfed infants.     

Nutrient intake and growth performance of older infants fed human milk

STUDY OBJECTIVE: To determine whether the ad libitum addition of solid foods to the diet of exclusively human milk-fed infants will increase energy intake and reverse the decline in weight-for-age percentiles observed during the exclusive breast-feeding period. DESIGN: Weekly or biweekly measures of growth were made longitudinally on a cohort of infants from birth to 36 weeks of age, and monthly measures of nutrient intake were made from 16 weeks of age until 10 weeks after solid foods were introduced into the diet. SUBJECTS: Volunteer mother-infant pairs from middle and upper income groups who met entry criteria, including the intention to breast-feed exclusively for at least for 16 weeks; 58 pairs entered and 45 pairs completed the study. INTERVENTION: Solid foods were introduced at a time determined by the mother and the pediatrician; solid foods from controlled lot numbers were provided for each infant. MEASUREMENTS AND MAIN RESULTS: After solid foods were added, daily human milk intake declined at a rate of 77 gm/mo (p less than 0.001). Milk composition did not change during the observation period. Daily total energy intake increased 29 kcal/mo, but no changes were noted in energy intake when consumption was normalized for body weight. Weight (National Center for Health Statistics percentiles) at 28 weeks was 13 percentiles lower than that at birth, and length at 28 weeks was 1 percentile lower than at week 1. Weight and length percentiles at 28 weeks, when compared with peak values at 8 weeks, had dropped 19 and 14 percentiles, respectively. CONCLUSIONS: Energy intake of human milk-fed infants did not increase after solid foods were added to their diet but was maintained at approximately 20% below recommended levels. Energy intake appeared to reflect infant demands. These data suggest that the recommendations for the energy requirements of infancy should be reevaluated. The growth pattern of exclusively breast-fed infants differs from that of the National Center for Health Statistics reference population. These observations raise questions about the adaptive response of human milk-fed infants to different levels of energy intake and about the estimations of energy requirements based on the sum of basal metabolism, activity, growth, and diet-induced thermogenesis.     

Low biotinidase activity in plasma of some preterm infants: possible source of false-positive screening results

Screening for biotinidase deficiency has been added recently to some national screening programmes. To clarify the problem of false-positive screening tests in premature infants, we have studied biotinidase activities in the plasma of this population in more detail. In 64 newborns (premature and term babies) biotinidase activities correlated positively with gestational age from the 2nd to the 30th day of life. During the 1st–3rd day the activities were below the normal adult range in all 64 infants. In 56 infants the activities subsequently increased gradually and reached the normal adult range during the 4th–40th day of life. In contrast, the biotinidase activities in eight preterm infants dropped during the 3rd–7th day of life. Impaired liver function as a possible cause for this finding could be ruled out in these infants. The lowest activities in these infants were measured during the 4th–6th day of life, i.e. unfortunately at a time when samples for the screening are normally taken. According to our data, 4–8 out of 48 preterm or small-for-date infants with biotinidase activities ranging from 4.7%–26% of the mean adult value would have given false-positive screening tests. A positive screening test was also obtained in a newborn and in an older unrelated child with a partial biotinidase deficiency. In these children the biotinidase activity did not rise but remained slightly below or at the lower range for heterozygotes (at 31% and 38% of the mean adult value). Currently we do not know whether such individuals are heterozygotes, or whether they have a variant of biotinidase deficiency. However, these children have developed normally without biotin therapy.Abbreviations DTT dithiothreitol     

Renal function correlates of postnatal diuresis in preterm infants

A characteristic pattern of fluid homeostasis occurs in the first week of life in many preterm infants. Initially, urine output is low independent of fluid intake, subsequently a diuresis occurs, and finally urine output begins to vary with intake. Renal clearance measurements were made during each of these three phases to elucidate the renal mechanisms involved. Periods during which the ratio of urine output to fluid intake was greater than or equal to 1 and urine output was greater than or equal to 3 mL/kg/h were defined as diuretic. Of 22 preterm infants studied from 12 to 120 hours of age, 17 had at least one period of diuresis. In these infants, urine output, fluid intake rate, output to intake ratio, glomerular filtration rate, and fractional sodium excretion were lowest at 12 to 24 hours of age. During diuresis, urine output tripled without a significant change in fluid intake so that output to intake increased to levels exceeding unity. Diuresis was associated with significant increases in glomerular filtration rate and fractional sodium excretion. By 108 to 120 hours of age, urine output decreased despite an increase in fluid intake. This was accompanied by a decrease in glomerular filtration rate. These results suggest that the initial antidiuretic phase is the result of a low fractional sodium excretion in the face of a low glomerular filtration rate. Subsequently, diuresis and natriuresis occur as a result of abrupt, nonmaturational increases in glomerular filtration rate and fractional sodium excretion. With cessation of diuresis, glomerular filtration rate and fractional sodium excretion decrease and water and electrolyte output begin to vary appropriately with intake.     

When children eat what they watch: impact of television viewing on dietary intake in youth

OBJECTIVES: To test whether increased television viewing is associated with increased total energy intake and with increased consumption of foods commonly advertised on television, and to test whether increased consumption of these foods mediates the relationship between television viewing and total energy intake. DESIGN: Prospective observational study with baseline (fall 1995) and follow-up (spring 1997) measures of youth diet, physical activity, and television viewing. We used food advertising data to identify 6 food groups for study (sweet baked snacks, candy, fried potatoes, main courses commonly served as fast food, salty snacks, and sugar-sweetened beverages). SETTING AND PARTICIPANTS: Five public schools in 4 communities near Boston. The sample included 548 students (mean age at baseline, 11.70 years; 48.4% female; and 63.5% white). MAIN OUTCOME MEASURES: Change in total energy intake and intake of foods commonly advertised on television from baseline to follow-up. RESULTS: After adjusting for baseline covariates, each hour increase in television viewing was associated with an additional 167 kcal/d (95% confidence interval, 136-198 kcal/d; P<.001) and with increases in the consumption of foods commonly advertised on television. Including changes in intakes of these foods in regression models provided evidence of their mediating role, diminishing or rendering nonsignificant the associations between change in television viewing and change in total energy intake. CONCLUSIONS: Increases in television viewing are associated with increased calorie intake among youth. This association is mediated by increasing consumption of calorie-dense low-nutrient foods frequently advertised on television.     

The quality of the diet in Malawian children with kwashiorkor and marasmus

Nutritionists have suggested that kwashiorkor is related to low dietary protein and/or antioxidant intake. This study explored the hypothesis that among Malawian children with severe malnutrition, those with kwashiorkor consume a diet with less micronutrient- and antioxidant-rich foods, such as fish, eggs, tomatoes and orange fruits (mango, pumpkin and papaya), than those with marasmus. A case-control method with a food frequency questionnaire was used to assess the habitual diet. Children with severe childhood malnutrition presenting to the central hospital in Blantyre, Malawi during a 3-month period in 2001 were eligible to participate. The food frequency questionnaire collected data about foods consumed by siblings <60 months of age in the home. It was assumed that the habitual diet of all siblings 1-5 years old in the same home was similar. Dietary diversity was assessed using a validated method, with scores that ranged from 0 to 7. Regression modelling was used to control for demographic and disease covariates. A total of 145 children with kwashiorkor and 46 with marasmus were enrolled. Children with kwashiorkor consumed less egg and tomato than those with marasmus: 17 (15) vs. 24 (31) servings per month for egg, mean (SD), P < 0.01 and 27 (17) vs. 32 (19) servings per month for tomato, P < 0.05. Children with kwashiorkor had a similar dietary diversity score as those with marasmus, 5.06 (0.99) vs. 5.02 (1.10), mean (SD). Further research is needed to determine what role consumption of egg and tomato may play in the development of kwashiorkor.     

Cord plasma alpha-fetoprotein values and neonatal jaundice

Umbilical cord plasma alpha-fetoprotein (AFP) values were determined in 127 infants with hyperbilirubinemia (56 glucose-6-phosphate dehydrogenase (G-6-PD) deficient and 71 G-6-PD normal) and 136 control subjects (73 G-6-PD deficient and 63 G-6-PD normal). The mean alpha-fetoprotein value of 173 +/- 35.2 (SD) mg/L for the group of infants with hyperbilirubinemia was significantly greater than that (122 +/- 21.7 mg/L) for the control infants (P less than .001). G-6-PD status and sex did not significantly affect the alpha-fetoprotein values. Using an alpha-fetoprotein level of 130 mg/L as a "cut-off" value, the incidence of false-positive results was 25.5% and the incidence of false-negative results was 11.8%. This test can be used as a screening procedure to detect infants at high risk for hyperbilirubinemia.     

Nutrient intakes of American infants and children fed cow's milk or infant formula

Between April 1984 and August 1984, a national survey, the Ross Laboratories Infant Nutrition Survey, was undertaken to assess patterns of food consumption of American infants ranging in age from 6.5 months to 13.4 months. Nutrient intakes of 865 infants were evaluated according to different foods (milk and milk products, non-iron-fortified formula, iron-fortified formula, infant cereal, commercial baby foods, and home-prepared table foods). Results indicated that most American infants consumed nutrients in appropriate amounts. However, a large proportion of infants who were fed a diet that included cow's milk received amounts of sodium, potassium, and chloride that exceeded the recommended safe and adequate ranges. The median intake of iron of infants fed either cow's milk or a non-iron-fortified formula was below the recommended dietary allowance; a low percentage of these infants received medicinal iron supplementation. The results also indicated that the median estimated renal solute load of the diet of infants fed cow's milk was approximately twice the amount of that of infants fed formula. These data may be useful in the development of nutritional programs for older infants.     

The most essential nutrient: defining the adequate intake of water

Although water is quantitatively the most import nutrient, there are no recommended dietary allowances (RDA) or adequate intake (AI) values. Based on 718 assessments of 24-hour total water intake, urine volume, and urine osmolality, individual hydration status was characterized in 479 healthy boys and girls of the DONALD study aged 4.0 to 6.9 years and 7.0 to 10.9 years. Mean 24-hour total water intake ranged from 0.90 mL/kcal to 0.96 mL/kcal, and median 24-hour urine osmolality ranged from 683 mosm/kg to 854 mosm/kg. A maximum urine osmolality of 830 mosm/kg (mean - 2 SD) in healthy children with a typical affluent Western-type diet was the physiologic criterion of the upper limit of euhydration. "Water reserve" (24-hour urine volume - hypothetical urine volume to excrete 24 urine solutes at a concentration of 830 mosm/kg) was a quantitative measure of individual 24-hour hydration status and ensuring euhydration in 97% of the subjects in each group; AI values of total water in the 4 age and sex groups ranged from 1.01 mL/kcal to 1.05 mL/kcal. These procedures to quantify 24-hour hydration status may prove valuable in investigating the effects on health of different states of euhydration.     

Significance of a positive urine group B streptococcal latex agglutination test in neonates

We assessed the clinical significance of a reactive urine latex agglutination (LA) test in neonates without bacteriologically confirmed group B streptococcal (GBS) infection. In a retrospective review of a 3 1/2-month period, during which 367 urine specimens from newborn infants evaluated for suspected sepsis were tested by LA, 25 infants (6.9%) with sterile blood cultures but positive urine LA test results were compared with a control group of 112 infants with both blood cultures and urine LA test results negative for GBS. When the data were studied with stepwise discriminant analysis, the only variables significantly associated with a positive urine LA test result were immature to total neutrophil ratios greater than or equal to 0.16 at 0 and 12 hours. The influence of mucosal GBS colonization on urine LA test results was then investigated prospectively in 98 healthy infants (83 born to mothers colonized with GBS and 15 born to mothers with negative GBS cultures). Eight (8.2%) of the infants studied, or 8 of 52 (15.4%) infants colonized with GBS, had a positive urine LA test result. GBS was isolated from urine cultures of all infants with a positive urine LA test result. A positive urine LA test result was associated with positive GBS rectal and vaginal cultures and with increased density of colonization at those sites. We conclude that contamination of bag specimens of urine with GBS from perineal and rectal colonization may produce a positive urine LA test result in an infant with no systemic sign of infection.     

Plasma and urine riboflavin during riboflavin-free nutrition in very-low-birth-weight infants

BACKGROUND: Very-low-birth-weight (VLBW; birth weight <1500 g) infants receive enteral and parenteral nutriture that provides greater daily riboflavin (vitamin B2) than does term infant nutriture, and elevated plasma riboflavin develops in these infants after birth. The purpose of this study was to measure plasma and urine riboflavin concentrations in VLBW infants during riboflavin-free nutrition. Our hypothesis was that elevated plasma riboflavin develops in VLBW infants because of high daily intake and immature renal riboflavin elimination. METHODS: Eighteen clinically healthy VLBW infants received parenteral nutrition and preterm infant formula during the first postnatal month. On postnatal days 10 and 28, the infants received specially prepared riboflavin-free enteral and parenteral nutrition for the 24-hour study period. Serial collections of plasma were made at time 0 and at 12 and 24 hours. Urine was collected continuously for the 24-hour period in 4-hour aliquots. Samples were analyzed for riboflavin concentration. RESULTS: During the 24-hour riboflavin-free study period on postnatal day 10, plasma riboflavin decreased 56% from 185 +/- 37 ng/mL (mean +/- SEM), and urine riboflavin decreased 75% from 3112 +/- 960 mg/mL. Similarly, on postnatal day 28, plasma riboflavin decreased 79% from 184 +/- 32 ng/mL, and urine riboflavin concentration decreased 91% from 5092 +/- 743 ng/mL during the 24-hour riboflavin-free study period. Riboflavin half-life (t(1/2)) was 18.5 hours on postnatal day 10 and decreased 48% by postnatal day 28. Riboflavin elimination was 145.1 +/- 20.6 mg/kg per day on postnatal day 10 and increased 40% by postnatal day 28. CONCLUSION: The VLBW infants who received parenteral nutrition and preterm infant formula had elevated plasma riboflavin on postnatal days 10 and 28. Plasma riboflavin t(1,2) was shorter and renal riboflavin elimination was greater on postnatal day 28 than on postnatal day 10. Plasma riboflavin was normal after 24 hours of riboflavin-free nutrition. The pattern of plasma and urine riboflavin in VLBW infants suggests a lower daily intake would maintain plasma riboflavin close to normal.     

Nutrient intakes in 2005 by non-breast fed French children of less than 36 months]

BACKGROUND: Knowledge of the nutritional consumption of very young children is of main interest, but little is known about the dietary status of French infants and toddlers. OBJECTIVE: To assess energy and nutrient intake and the adequacy of diet of French infants and toddlers. DESIGN AND SETTING: A national cross-sectional survey was conducted in France from January to March 2005, using proportionate quota sampling based on the age of the children, the occupation of the mother, and the family socioeconomic category. SUBJECTS: Seven-hundred and six children were allocated to 11 age subgroups ranging from one to three months to 31-36 months. Totally or partially breastfed infants were excluded. ANALYSES PERFORMED: Individual consecutive 3-day weight food records were converted into energy intake and intake of 24 nutrients according to food composition databases recently updated for 1260 standard foods and all the formulae and specific baby foods manufactured and marketed in France in 2005. RESULTS: Mean daily energy intake in 2005 was above the estimated average requirement up to seven months of age, but was lower after one year. Protein, fat, and carbohydrate intakes were adequate, while calcium, magnesium, phosphorus and B group vitamins were above the recommended dietary allowances for all 11 subgroups. However, for toddlers over 12 months of age, some may have had an inadequate intake of alpha-linolenic acid, vitamin E, vitamin C, iron and zinc, whereas mean sodium intake was above the adequate intake for all age subgroups. CONCLUSIONS: The diet of French infants was adequate for a large proportion of children and satisfied most of their nutritional requirements. However, the intake of iron and alpha-linolenic acid in particular needs to be improved for some French toddlers.     

Dietary aspects of pregnant women in rural areas of Northern India

The aim of this article is to document the current dietary profile of pregnant women in rural areas of Delhi. In order to explore the diet the combination of quantitative (24-h recall method) and qualitative methods (food frequency method) were used. The mean intake of macronutrients and micronutrients, namely, iron, folic acid and Vitamin C which play an important role in the pathophysiology of nutritional anaemia during pregnancy was calculated from the foodstuffs, using Nutritive Value of Indian Foods. The preferences and avoidance of various foods by the pregnant women were also elicited. The data were analysed using Epi Info 3.4. The intake of calories, protein, iron, folic acid and Vitamin C was found to be less than the recommended dietary allowance in 100%, 91.2%, 98.2%, 99.1% and 65.8% of pregnant women respectively. Folic acid intakes were significantly lower in younger, primiparous and poorly educated women from low-income families. Vitamin C intake was lower among non-Hindus only. The overall data suggested the presence of food gap rather than isolated deficiency of any particular nutrient.     

膳食多样化与婴儿微量营养素摄入及其体格生长的相关性

目的 验证简易的膳食多样化分数(DDS)和食物种类多样化分数(FVS)对评估婴儿膳食质量的有效性.方法 选取足月、单胎、12月龄健康婴儿,针对父母及照料者调查婴儿喂养情况.调查当日测量获得婴儿体格牛长数据.按照婴儿1个月内各类食物摄入频度和种类计算DDS;按照婴儿1周内摄入食物种类计算FVS.详细定量记录婴儿连续3 d的膳食,并运用膳食分析软件计算各种营养素摄入量.结果 共236例12月龄婴儿进入分析.婴儿体格牛长良好,平均按年龄身长、按年龄体质量、按身长体质量的Z评分(LAZ、WAZ、WLZ)分别达到0.44±0.88、0.78±0.81、0.79±0.83.婴儿热能、蛋白质及绝大多数微量营养素的营养素适宜比例(NAR),即膳食摄入量与WHO推荐摄入量的比值,均超过100%.DDS、FVS、DDS+FVS高分组婴儿的LAZ、WAZ、WLZ均高于相应的低分组婴儿,但差异均无统计学意义.DDS和FVS分别与多种微屠营养素的NAR(%)呈显著正相关,DDS+FVS则与更多的微量营养素的NAR(%)呈显著正相关.婴儿体格生长指标与多项微量营养素的NAR(%)呈显著正相关.结论 简易的DDS、FVS评分可用于评价婴儿的膳食质量,DDS+FVS可能更有效.增加食物多样性有利于婴儿获得全面平衡的营养,促进其生长.     

Morphine metabolism in acutely ill preterm newborn infants.

To examine the manner in which morphine is metabolized in acutely ill premature infants, we measured the levels of morphine, morphine-3- and -6-glucuronides, and codeine in timed urine specimens and paired plasma specimens at 4 hours and 24 hours after a single dose of morphine in 16 preterm infants (less than 32 weeks of gestational age). A large amount of unmetabolized morphine was found in the urine in 13 (81.2%) of the 16 infants at 4 hours; in 12 of them, morphine was excreted even at 24 hours. Urinary morphine levels varied greatly; the coefficient of variation was 130% at 4 hours and 118% at 24 hours. Codeine was not found in any of the infants. In 10 (62.5%) of the 16 infants, at least one metabolite was found in either plasma or urine. Plasma and urinary levels of morphine conjugates also varied greatly among these 10 infants (coefficient of variation: 109% to 317%). All six infants (37.5%) who had no metabolites excreted large amounts of unmetabolized morphine in the urine for up to 24 hours. Birth weight, gestational age, postnatal age, systemic blood pressure, and other clinical or physiologic variables did not differ significantly between the 10 infants who had morphine conjugates and the six who did not. We conclude that (1) nearly two thirds of acutely ill preterm infants born at less than 32 weeks of gestational age conjugate morphine; (2) irrespective of their ability to produce morphine conjugates, preterm infants excrete large amounts of morphine unmetabolized, as late as 24 hours after a single dose; (3) morphine handling patterns are highly variable among premature infants, and no obvious factors account for the variability; and (4) such variability in morphine handling in general, and the production of the highly potent morphine-6-glucuronide in particular, could explain the variance in morphine pharmacokinetic measures and in the clinical responses to morphine during the newborn period.     

New Ballard Score, expanded to include extremely premature infants

The Ballard Maturational Score was refined and expanded to achieve greater accuracy and to include extremely premature neonates. To test validity, accuracy, interrater reliability, and optimal postnatal age at examination, the resulting New Ballard Score (NBS) was assessed for 578 newly born infants and the results were analyzed. Gestational ages ranged from 20 to 44 weeks and postnatal ages at examination ranged from birth to 96 hours. In 530 infants, gestational age by last menstrual period was confirmed by agreement within 2 weeks with gestational age by prenatal ultrasonography (C-GLMP). For these infants, correlation between gestational age by NBS and C-GLMP was 0.97. Mean differences between gestational age by NBS and C-GLMP were 0.32 +/- 1.58 weeks and 0.15 +/- 1.46 weeks among the extremely premature infants (less than 26 weeks) and among the total population, respectively. Correlations between the individual criteria and C-GLMP ranged from 0.72 to 0.82. Interrater reliability of NBS, as determined by correlation between raters who rated the same subgroup of infants, ws 0.95. For infants less than 26 weeks of gestational age, the greatest validity (97% within 2 weeks of C-GLMP) was seen when the examination was performed before 12 hours of postnatal age. For infants at least 26 weeks of gestational age, percentages of agreement with C-GLMP remained constant, averaging 92% for all postnatal age categories up to 96 hours. The NBS is a valid and accurate gestational assessment tool for extremely premature infants and remains valid for the entire newborn infant population.