Benefits of supplemented preterm formulas on insulin sensitivity and body composition after discharge from the neonatal intensive care unit.

OBJECTIVE: To evaluate body composition and fasting insulin level in preterm infants receiving preterm formulas (higher protein plus docosahexaenoic acid) for longer periods compared with a recent historical cohort receiving these formulas for shorter periods. STUDY DESIGN: A total of 95 infants fed preterm formula for 6 months or longer (postdischarge formula group) and 87 infants fed preterm formula only during their hospital stay (hospital formula group) were included in this arm of the study. RESULTS: Bone mineral density, content, and lean mass were not different at 1 year and 2 years. However, in the postdischarge formula group, total fat mass (%) was lower by the second year (19.3% ± 5.3% vs 21.7% ± 4.2%; P < .01), trunk fat was lower by the first year (14.7% ± 5.0% vs 16.9% ± 4.9%; P < .005) and at the second year (14.1% ± 5.7% vs 17.2% ± 4.7%; P < .001), and fasting insulin was lower by the first year (13.2% ± 7.1% vs 17.2% ± 13.6% mIU/L; P = .06) and at the second year (13.6% ± 6.1% vs 26.4% ± 14.2%; P < .001). CONCLUSION: Preterm infants fed formulas enriched with docosahexaenoic acid may have a better subsequent metabolic profile.

Cost-effectiveness of a folic acid fortification program in Chile.

OBJECTIVE: Periconceptional intake of folic acid reduces the risk of neural tube defects (NTDs), a frequent birth defect that can cause significant infant mortality and disability. In Chile, fortification of wheat flour with folic acid has resulted in significant reduction in the risk of anencephaly and spina bifida. We investigated the cost-effectiveness implications of this policy. METHODS: We conducted an ex-post economic analysis of this intervention. Estimates of the effect of fortification in decreasing NTDs and deaths were derived from a prospective evaluation. The costs of fortification and provision of medical care to children with spina bifida in Chile were based on primary data collection. FINDINGS: The intervention costs per NTD case and infant death averted were I$ 1200 and 11,000, respectively. The cost per DALY averted was I$ 89, 0.8% of Chile's GDP per capita. Taking into account averted costs of care, fortification resulted in net cost savings of I$ 2.3 million. CONCLUSION: Fortification of wheat flour with folic acid is a cost-effective intervention in Chile, a middle income country in the post-epidemiological transition. This result supports the continuation of the Chile fortification program and constitutes valuable information for policy makers in other countries to consider.

Parenteral nutrition-associated cholestasis in neonates: multivariate analysis of the potential protective effect of taurine.

BACKGROUND: Neonates receiving parenteral nutrition (PN) are at risk for PN-associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. METHODS: This study was part of a prospective, randomized, multi-institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. RESULTS: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [-0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79-5.11] for neonates not receiving taurine, approaching significance, p = .07). Taurine significantly reduced PNAC in infants with necrotizing enterocolitis (NEC; estimated maximum CB 4.04 mg/dL [2.85-5.23], NEC infants receiving taurine, vs 8.29 mg/dL [5.61-10.96], NEC infants not receiving taurine, p < .01). There were too few neonates with surgical anomalies to evaluate the effect of taurine in this group. CONCLUSIONS: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.

Community-based randomized double-blind study of gastrointestinal effects and copper exposure in drinking water.

We assessed gastrointestinal effects in 1,365 adults exposed to either < 0.01 (controls), 2, 4, or 6 mg copper/L of drinking water for 2 months in a randomized, double-blind community-based study. The risk of symptoms increased with increasing Cu exposure and decreased with time. The best model by counting-process analysis included Cu concentration and sex. The risk of symptoms remained significantly higher in women than in men during weeks 1-4 for all concentrations tested; at week 1 comparison with the < 0.01-mg/L group showed that differences became significant in women at 4 mg/L [relative risk (RR) = 1.53; 95% confidence interval (CI), 1.02-2.05), and in men at 6 mg/L (RR = 1.9; 95% CI, 1.02-2.79). At week 2 for men and week 4 in women, the Cu concentration required to obtain significant differences on symptom report was > 6 mg Cu/L. We conclude that exposure to Cu in drinking water results in gastrointestinal symptoms, which are modulated by Cu concentration, time, and sex.

Lower whole blood ionized magnesium concentrations in hypocalcemic infants of gestational diabetic mothers.

Infants of insulin dependent (class B and above) diabetic mothers (IDM's) have a high rate of neonatal hypocalcemia (NHC) and hypomagnesemia. We carried out this study to test the hypotheses that: (1) infants of gestational diabetic (class A) mothers (IGDM's) are also at risk for NHC and (2) NHC in IGDM's relates to decreased whole blood Mg(2+) concentration. Thirty one term infants born to gestational diabetic mothers of classes A1 (diet controlled, n = 23) and A2 (requiring insulin, n = 8) of White's classification, were compared at 24 +/- 2 hours of age to 32 healthy, appropriate for gestational age controls, born after uncomplicated pregnancy, labor and delivery. Whole blood Mg(2+) and Ca(2+) were measured using an ion-specific electrode (Nova 8, Nova biomedical, Waltham, MA). The rate of NHC was higher in the IGDM group as compared to the control group (9 out of 31 [29%] vs. 1 out of 32 [3.1%] infants; p < 0.01). Whole blood Mg(2+) was lower in the IGDM group than in controls (p < 0.05). In multiple regression analysis, when Ca(2+) was used as the dependent variable and Mg(2+), diabetes class, gestational age, macrosomia and one minute Apgar scores were the independent variables, only Mg(2+) and diabetes class were significant (R2 = 0.4374; p < 0.01). Our results are consistent with the theory that Mg deficiency plays a role in NHC encountered in IGDM's, similar to what occurs in infants of insulin-dependent diabetic mothers.

The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response.

Necrotizing enterocolitis (NEC) is a devastating neonatal intestinal inflammatory disease, occurring primarily in premature infants, causing significant morbidity and mortality. The pathogenesis of NEC is associated with an excessive inflammatory IL-8 response. In this study, we hypothesized that this excessive inflammatory response is related to an immature expression of innate immune response genes. To address this hypothesis, intestinal RNA expression analysis of innate immune response genes was performed after laser capture microdissection of resected ileal epithelium from fetuses, NEC patients and children and confirmed in ex vivo human intestinal xenografts. Changes in mRNA levels of toll-like receptors (TLR)-2 and -4, their signaling molecules and transcription factors (MyD88, TRAF-6 and NFκB1) and negative regulators (SIGIRR, IRAK-M, A-20 and TOLLIP) and the effector IL-8 were characterized by qRT-PCR. The expression of TLR2, TLR4, MyD88, TRAF-6, NFκB1 and IL-8 mRNA was increased while SIGIRR, IRAK-M, A-20 and TOLLIP mRNA were decreased in fetal vs. mature human enterocytes and further altered in NEC enterocytes. Similar changes in mRNA expression were observed in immature, but not mature, human intestinal xenografts. Confirmation of gene expression was also validated with selective protein measurements and with suggested evidence that immature TRL4 enterocyte surface expression was internalized in mature enterocytes. Cortisone, an intestinal maturation factor, treatment corrected the mRNA differences only in the immature intestinal xenograft. Using specific siRNA to attenuate expression of primary fetal enterocyte cultures, both TOLLIP and A-20 were confirmed to be important when knocked down by exhibiting the same excessive inflammatory response seen in the NEC intestine. We conclude that the excessive inflammatory response of the immature intestine, a hallmark of NEC, is due to a developmental immaturity in innate immune response genes.

Compartmental analyses of 2H5-alpha-linolenic acid and C-U-eicosapentaenoic acid toward synthesis of plasma labeled 22:6n-3 in newborn term infants.

BACKGROUND: During early postnatal development, the nervous system accretes docosahexaenoic acid (DHA; 22:6n-3), a highly unsaturated n-3 (omega-3) fatty acid (FA) used in the formation of neural cell membranes. DHA, which is present in human breast milk, may also be biosynthesized from n-3 FAs such as 18:3n-3 [alpha-linolenic acid (ALA)] or 20:5n-3 [eicosapentaenoic acid (EPA)]. An important concern is to what extent these precursors can supply DHA to the developing infant. OBJECTIVE: We analyzed measurements of fractional percentages of plasma (2)H(5)-ALA and (13)C-U-EPA directed toward the synthesis of labeled 22:6n-3 in 11 newborn infants by using compartmental modeling procedures. DESIGN: One-week-old infants received doses of (2)H(5)-ALA and (13)C-U-EPA ethyl esters enterally. We drew blood from the infants periodically and analyzed the plasma for endogenous and labeled n-3 FAs. From the time-course concentrations of the labeled FAs, we determined rate constant coefficients, fractional synthetic rates, and plasma turnover rates of n-3 FAs. RESULTS: In infants, approximately 0.04% of the (2)H(5)-ALA dose converted to plasma (2)H(5)-EPA. Plasma (2)H(5)-EPA and (2)H(5)-22:5n-3 [docosapentaenoic acid (DPA)] efficiently converted to (2)H(5)-DPA and (2)H(5)-DHA, respectively. The percentage of plasma (13)C-U-EPA directed toward the synthesis of (13)C-DHA was lower than the percentage of plasma (2)H(5)-EPA that originated from (2)H(5)-ALA. CONCLUSIONS: Endogenously synthesized EPA was efficiently converted to DHA. In comparison, preformed EPA was less efficiently used for DHA biosynthesis, which suggests a differential metabolism of endogenous EPA compared with exogenous EPA. However, on a per mole basis, preformed EPA was 3.6 times more effective toward DHA synthesis than was ALA. Newborns required an intake of approximately 5 mg preformed DHA. kg(-1) x d(-1) to maintain plasma DHA homeostasis.

Are research priorities in Latin America in line with the nutritional problems of the population?

OBJECTIVE: Concordance of nutritional research priorities with the related burden of disease is essential to develop cost-effective interventions to address the nutritional problems of populations. The present study aimed to evaluate whether nutrition research priorities are in agreement with the population's nutritional problems in Latin America. DESIGN: The epidemiological profile was contrasted with the research priorities and research produced by academic institutions for each country. Qualitative analysis of research production by type of contribution to problem solving was also conducted. SETTINGS: Nine Latin American countries. RESULTS: Obesity (high body mass index (BMI)) and micronutrient deficiencies (anaemia) emerged as key problems, followed by stunting, breast-feeding/lactation and low birth weight. Wasting in children and women (low BMI) was uncommon. Concordance of ranked research priorities with the epidemiological profile of the country was generally good for nutrition-related chronic diseases, micronutrients and low birth weight, but not for undernutrition, stunting and breast-feeding. Studies on the efficacy and effectiveness of interventions were uncommon. CONCLUSIONS: The present research agenda insufficiently supports the goal of public health nutrition, which is to ensure the implementation of cost-effective nutrition programmes and policies. A more rational approach to define research priorities is needed.

Compartmental analyses of plasma 13C- and 2H-labeled n-6 fatty acids arising from oral administrations of 13C-U-18:2n-6 and 2H5-20:3n-6 in newborn infants.

Efficacy of (13)C-U-18:2n-6 and (2)H(5)-20:3n-6 toward synthesis of labeled-20:4n-6 was studied in newborn infants utilizing compartmental models of plasma labeled n-6 fatty acids (FA). Ten infants received oral doses of (13)C-U-18:2n-6 and (2)H(5)-20:3n-6 ethyl esters (100 and 2 mg/kg, respectively). Rate constant coefficients and half-lives (t((1/2))) of n-6 FA were determined from the time-course concentrations of labeled-FA. Plasma n-6 FA values approximated steady state concentrations. Synthetic and utilization rates were calculated. Eight percent (range, 2-21%) of plasma (13)C-U-18:2n-6 was used for synthesis of (13)C-18:3n-6, -20:2n-6, and -20:3n-6. Seventy percent of (13)C-20:3n-6 (mean, CV: 0.26) was available for synthesis of (13)C-20:4n-6. The percentage of (2)H(5)-20:3n-6 converted to (2)H(5)-20:4n-6 was lower (mean: 26%, p < 0.02) than the (13)C-labeled analogue. Turnover of 18:2n-6 in subjects and of 20:4n-6 in plasma was 4.2 g/kg/d (CV: 0.58) and 4.3 mg/kg/d (CV: 0.81), respectively. Intake of 18:2n-6 and 20:4n-6 were estimated to be 3.0 g/kg/d (+/-1.7) and 2.8 mg/kg/d (+/- 2.2), respectively. Infants required additional 18:2n-6 and 20:4n-6 (mean: 1.2 g and 1.5 mg/kg/d) above predicted intake amounts to maintain plasma concentrations of 18:2n-6 and 20:4n-6, in order to spare FA from fat stores.

Infants with intrauterine growth restriction have impaired formation of docosahexaenoic acid in early neonatal life: a stable isotope study.

This study evaluated the arachidonic acid (AA) and docosahexaenoic acid (DHA) formation from d5-labeled linoleic acid (d5-LA) and alpha-linolenic acid (d5-LNA) precursors in infants with intrauterine growth restriction (IUGR) compared with control groups matched by gestational age (GA) or birth weight. We compared DHA and AA formation from deuterated precursors d5-LA and d5-LNA in 11 infants with IUGR with 13 and 25 control subjects who were appropriate for GA and matched by GA and by birth weight, respectively. After an enteral administration of d5-LA and d5-LNA, we determined unlabeled and d5-labeled fatty acids at 24, 48, and 96 h in plasma. Absolute concentrations and area under the curve (AUC) over the 96-h study were used for analysis. Absolute concentration of d5-DHA and the product/precursor ratio of the d5-labeled AUCs indicated a less active DHA formation from LNA in infants with IUGR compared with their GA-matched (2-fold) and birth weight-matched (3-fold) control subjects. The ratios of eicosapentaenoic and n-3 docosapentaenoic acid to DHA were also affected. Similar evaluation for the n-6 series was not significant. DHA metabolism is affected in infants with IUGR; the restricted DPA to DHA conversion step seems to be principally responsible for this finding.

Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis.

OBJECTIVE: To determine whether cholecystokinin-octapeptide (CCK-OP) would prevent or ameliorate parenteral nutrition-associated cholestasis (PNAC) among high-risk neonates treated with total parenteral nutrition. STUDY DESIGN: This was a multicenter, double-blind, randomized, controlled trial conducted between 1996 and 2001. PATIENTS: Neonates at risk for the development of PNAC included very low birth weight neonates and those with major surgical conditions involving the gastrointestinal tract. SETTING: Tertiary care hospitals. INTERVENTION: Patients were randomized to receive CCK-OP (0.04 mug/kg per dose, twice daily) or placebo. Eligible infants were all <30 days of age. Patients were enrolled within 2 weeks after birth or within 7 days after surgery. OUTCOME MEASURES: The primary outcome measure was conjugated bilirubin (CB) levels, which were measured weekly. Secondary outcome measures included incidence of sepsis, times to achieve 50% and 100% of energy intake through the enteral route, number of ICU and hospital days, mortality rate, and incidences of biliary sludge and cholelithiasis. RESULTS: A total of 243 neonates were enrolled in the study. CCK-OP administration did not significantly affect CB levels (1.76 +/- 3.14 and 1.93 +/- 3.31 mg/dL for CCK-OP and placebo groups, respectively; mean +/- SD). Secondary outcome measures also were not significantly affected by the study drug. CONCLUSIONS: Use of CCK-OP failed to reduce significantly the incidence of PNAC or levels of CB. CCK-OP had no effect on other secondary measures and should not be recommended for the prevention of PNAC.

Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials.

Healthy term infants who are not breast-fed may need long-chain polyunsaturated fatty acids (LCPUFA) in their feeding, based on the changes in plasma and tissue fatty composition. However, consistent functional effects across different studies conducted over the past two decades has been more difficult to document. The interpretation of these data has scientific and public interest with the introduction of LCPUFA supplemented formula. There are 14 controlled trials in term infants that have included formula feeding with or without LCPUFA and functional assessment of visual and other measures of neural development; in addition, 7 have evaluated specific measures related to cognitive development. We chose to examine the effect of DHA dose provided daily on the development of visual acuity to explain the differences in visual acuity responses across randomized studies. A "meta-regression" was performed with the use of a DHA effective dose as the independent variable and visual acuity at 4 months as the dependent variable. Since the two main dietary determinants of DHA status are the LNA provided and the preformed DHA consumed, we defined DHA equivalent dose across studies by assuming a 1%, 5%, and 10% conversion of LNA to DHA. Results indicate a strong and significant effect of DHA equivalent dose on magnitude of the visual acuity response at all conversions tested; greatest significance was found when using a 10% bioequivalency (r(2)=0.68, and P=.001). We conclude that there is a significant relation between the total DHA equivalents provided and effectiveness as defined by visual acuity measurements at 4 months of age.

Epidemiology of neonatal necrotising enterocolitis: a population-based study.

We examined the birthweight-, gender- and race-specific incidence as well as the biodemographic and clinical correlates of necrotising enterocolitis (NEC) in a well-defined six-county perinatal region in upstate New York. We conducted a retrospective, 8-year population-based survey to identify all cases of proven NEC (modified Bell stage II and above) in the area's regional neonatal intensive care unit (NICU). The denominator used to calculate the incidence was obtained from the Statewide Planning Research Cooperative System. Incidence was expressed as cases per 1000 live births. A total of 85 documented cases of proven NEC was identified in a six-county perinatal region that experienced 117 892 live births during the 8-year period. The average annual incidence was 0.72 cases per 1000 live births [95% CI 0.57, 0.87 per 1000 live births]. The highest incidence of NEC occurred among infants weighing 750-1000 g at birth and declined with increasing birthweight. The urban county had a 1.53 times higher risk of NEC than rural counties [95% CI 0.9, 2.6]. The overall incidence of NEC for non-Hispanic blacks was significantly greater than that for non- Hispanic whites (2.2 vs. 0.5 cases per 1000 live births, P = 0.00). The differences remained statistically significant even after correction for birthweight. Most cases (93%) in this series were preterm (gestational age <37 weeks). Only two patients were never fed before the diagnosis of NEC was confirmed. Positive blood cultures were documented in 27% of the cases with a predominance of Gram-negative enteric micro-organisms. NEC remains an important health problem especially for preterm infants and the non-Hispanic black population.

Morbilidad y mortalidad del recién nacido menor de 1500 g. Experiencia de un hospital regional de la red internacional Vermont Oxford / Morbility and mortality in less that 1500 gr newborns, regional experience of the international Vermont Oxford web

La creación de redes de cuidado intensivo neonatal permite aplicar metodologías de ôbenchmarkingõ, las cuales están diseñadas para realizar análisis comparativo de indicadores de morbimortalidad relevantes entre las unidades participantes con el objetivo final de mejorar la calidad del cuidado intensivo neonatal. En el año 2004 el hospital Sótero del Río (HSR) se unió a la red internacional del Vermont Oxford (VON). Objetivo: presentar los resultados comparativos de morbilidad y mortalidad del HSR en el primer año de participación en la red. Material y métodos: la población evaluada incluye todos los recién nacidos vivos con peso al nacer entre 501 y 1.500 g, información de morbimortalidad relevante se registra prospectivamente siguiendo metodología y definiciones estandarizadas por la red VON. Resultados: 38.895 recién nacidos se ingresaron a la red; 124 pertenecen al HSR. La sobrevida total fue menor en el HSR (73 por ciento) comparada con VON (85 por ciento). Las tasas de requerimiento de 02 a las 36 semanas (51 por ciento) y HIV severa (16 por ciento) en el HSR son superiores a los valores observado en el percentil 75 de la VON. Las tasas de ROP severa (5 por ciento) y ECN (4 por ciento) se encuentran entre los valores de los rangos intercuartiles de la VON, mientras que infección nosocomial (2 por ciento) es inferior al percentil 25 de la red. Conclusiones: los resultados permiten evaluar las ventajas de pertenecer a una red internacional principalmente de unidades localizadas en países desarrollados, que ofrece metodologías para el registros de información y análisis estadístico de indicadores relevantes de alta calidad, en identificar áreas del cuidado neonatal que requieren mejorarse y así mejorar la calidad.

Reanimación neonatal / Neonatal resuscitation

La reanimación cardiopulmonar del recién nacido presenta desafíos diferentes a la reanimación del adulto o del niño mayor, especialmente por los dramáticos cambios fisiológicos que ocurren al momento de nacer. En los últimos años se han desarrollado guías universales basadas en evidencia para una adecuada reanimación. El presente artículo es una revisión y resumen de dichas recomendaciones

Correlación clinicopatológica perinatal en el Hospital de San José de Bogotá

Teniendo en cuenta la disponibilidad de datos en los archivos de autopsias del servicio de patología y los datos clínicos correspondientes, decidimos realizar un estudio descriptivo longitudinal de tipo retrospectivo, utilizando esta información, obtenida a través de los diez años comprendidos entre enero de 1980 y diciembre de 1989. Se plantearon como objetivos determinar la correlación clinicopatológica de los diagnósticos perinatales; presentar la distribución de los diagnósticos anatomopatológicos y realizar un diagnóstico de la mortalidad perinatal teniendo en cuenta variables como: sexo, edad gestacional, edad postnatal, Apgar, peso y días de hospitalización. Proponemos el uso habitual de esa clasificación para todas las muertes perinatales, con el fin de facilitar estudios posteriores que contribuyan a enriquecer los conocimientos del personal médico involucrado en el manejo de estos pacientes. Los datos en los que se basa este estudio se codificaron según la clasificación de mortalidad perinatal adoptada en 1958 por el estudio de mortalidad perinatal británico (British Perinatal Mortality Survey) revisada por Hey, Lloyd y Wiggleswoth en 1986.

Prevalencia de farmacodependencia en estudiantes de sexto ano de bachillerato de colegios oficiales y privados. Segundo semestre 1984. Barranquilla, Colombia / Prevalence of drug dependence in senior high school students from governamental and private schools. Second semester 1984. Barranquilla, Colombia

Con el fin de describir el nivel de farmacodependencia de los estudiantes de sexto ano de bachillerato de los colegios de Barranquilla, la magnitud del problema, las variables asociadas con el fenomeno y con el proposito de estructurar programas preventivos, se realizo un estudio epidemiologico de tipo descriptivo, de corte, en una muestra representativa durante el periodo del II semestre de 1984. Para la recoleccion de la informacion se elaboro un formulario, el cual fue previamente probado. Los resultados nos muestran que la prevalencia de farmacodependencia en la poblacion estudiada de 123 por mil, estuvo relacionada en mayor proporcion, con los alumnos cuyos padres eran de temperamento violento, no cumunicativos y en aquellos cuya composicion familiar era inestable. Segun clase economica, los sicofarmacos de mayor consumo fueron: la cocaina, en la clase alta y la marihuana en la clase baja. En ambas clases el "bazooko" ocupo el segundo lugar. Los resultados del trabajo nos indican que una serie de factores de riesgo se asocian al cosumo de sicofarmacos y por ello, los autores consideran que son factibles programas de prevencion