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Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00.

OBJECTIVE: Fewer than 50% of neonates with an umbilical arterial pH < 7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates. STUDY DESIGN: In this case-control study both cases and controls had an umbilical arterial cord pH < 7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH < 7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes. RESULTS: We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH < 7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit > or = 16 mmol/L and a 5-minute Apgar score < 7 had a sensitivity and a specificity of 79% and 80.8%, respectively. CONCLUSION: Neonatal morbidity in neonates with an umbilical arterial cord pH < 7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.

Acidosis↗

Identification of Macrosomic, normal and intrauterine growth retarded neonates using the modified Neonatal Growth Assessment Score.

OBJECTIVE: Separation of Macrosomic, normal and intrauterine growth retarded (IUGR) neonates using the modified Neonatal Growth Assessment Score (NGAS). METHODS: A sample of 23 neonates with evidence of growth acceleration and 74 neonates classified as normal or IUGR in a previous study was used in this investigation. The prenatal growth of all neonates had been studied longitudinally with ultrasound. From the data collected, Rossavik models describing the growth trajectories of head circumference (HC), abdominal circumference (AC), thigh circumference (ThC), femur diaphysis length, head cube (A) and abdominal cube (B) were specified. These models were used to predict birth weight (WT), crown-heel length (CHL), HC, AC and ThC at birth. Actual birth measurements of WT, CHL, HC, AC and ThC were evaluated using age-specific normal size curves and compared to predicted measurements by means of the growth potential realization index (GPRI). GPRI values were evaluated by comparison to previously established normal ranges and used to calculate Neonatal Growth Assessment Scores (NGAS(5)). NGAS(5) values, together with assessments of anatomical measurements and GPRI values, were used to establish macrosomic, normal and IUGR groups. Principal components analysis was applied to the sets of GPRI values available for each neonate to provide a principal component score for separating macrosomic and normal neonates (m(2)NGAS(51)) or one to separate macrosomic, normal and IUGR neonates (m(3)NGAS(51)) using linear discriminant analysis. The groups identified by these multivariate methods were compared to the original classification and their characteristics evaluated. RESULTS: The m(2)NGAS(51) and a boundary value of 207.5% separated macrosomic and normal neonates with an accuracy of 97.3%. The m(3)NGAS(51) and boundary values of 210.0 and 182.5% separated macrosomic, normal and IUGR neonates with an accuracy of 96.9%. No single GPRI value or anatomical measurement could achieve these levels of accuracy. All normal infants were AGA but only 45.5% of the IUGR group were SGA and only 60.9% of the macrosomic group were LGA. Thirteen different types of IUGR and eleven different types of macrosomia were identified based on GPRI values. CONCLUSION: The modified NGAS accurately separates macrosomic, normal and IUGR neonates although growth abnormalities are expressed in different ways in different individuals.

Adult↗

Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens.

Neonates do not respond to thymus-independent (TI) antigens (Ag), making them vulnerable to infection with encapsulated bacteria. The antibody (Ab) response of adult and neonatal B cells to TI Ag requires certain cytokines, which are provided by T cells or macrophages (MPhi). Lipopolysaccharide (LPS) failed to induce neonatal MPhi to produce interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha) mRNA and to secrete IL-1beta, IL-12, and TNF-alpha. However, LPS induced neonates to secrete some IL-6 and three- to fivefold more IL-10 than adults. Accordingly, adding adult but not neonatal MPhi could restore the response of purified adult B cells to trinitrophenol (TNP)-LPS, a TI Ag. Increased IL-10 is causally related to decreased IL-1beta and IL-6 production, as IL-10(-/-) neonatal MPhi responded to LPS by secreting more IL-1beta and IL-6 than wild-type (WT) neonatal MPhi. When cultures were supplemented with a neutralizing Ab to IL-10, WT neonatal MPhi secreted increased amounts of IL-6 and allowed neonatal MPhi to promote adult B cells to mount an Ab response against TNP-LPS. Thus, neonates do not respond to TI Ag as a result of the inability of neonatal MPhi to secrete cytokines, such as IL-1beta and IL-6, probably as a result of an excess production of IL-10. This dysregulated cytokine secretion by neonatal MPhi may be a result of a reduction in expression of Toll-like receptor-2 (TLR-2) and TLR-4 and CD14.

Animals↗

Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress.

OBJECTIVE: To analyze the kynurenine and methoxyindole metabolic pathways of tryptophan in order to identify changes in premature neonates and in neonates suffering from fetal distress. METHODS: One hundred and twelve neonates were assigned to three groups: normal neonates (control group), preterm neonates (neonates born before the 37th gestational week) and neonates suffering from fetal distress. Each of these groups was then divided in two subgroups according to the time of birth corresponding with the time of blood sampling: a diurnal subgroup, comprising neonates whose blood was sampled between 0900 and 2100 h, and a nocturnal subgroup, comprising neonates whose blood was sampled between 2100 and 0900 h. Blood samples from the umbilical artery and vein were taken in the delivery room at birth from each neonate for measurement of melatonin, the main methoxyindole pathway metabolite. Urine samples were collected from 0900 to 2100 h (diurnal groups) and from 2100 to 0900 h (nocturnal groups), and the presence of kynurenic acid, xanturenic acid, 3-hydroxyantranilic acid, L-kynurenine and 3-hydroxykynurenine determined. RESULTS: The results show the existence of diurnal/nocturnal differences in the concentration of melatonin in cord blood and in the urinary excretion of kynurenines. In normal neonates, the production of methoxyindoles (determined as melatonin) is decreased during the day and increases at night, whereas production of kynurenines is high during the day, decreasing at night. In the fetal distress group, a significant increase in the umbilical artery concentration of melatonin was found. This group also showed a reduction in L-kynurenine concentrations in the diurnal and nocturnal groups, and an increase in xanturenic acid and 3-hydroxyantranilic acid during the day. Correlation and regression studies confirmed that the differences in the day/night pattern of the tryptophan metabolic pathways were greater in normal neonates than in the preterm and fetal distress groups. CONCLUSIONS: The results indicate the existence of an imbalance in tryptophan metabolites in preterm infants and those with fetal distress, blunting the normal diurnal/nocturnal rhythm of both melatonin and kynurenines.

Acute Disease↗

Neonatal deaths in Alabama. II. Policy and research implications derived from a comparison of birth weight-specific state and medical center neonatal mortality rates.

An analysis of Alabama's recent neonatal mortality rate was performed to answer questions pertaining to projected changes in the neonatal mortality rate in the next decade. With current technology these questions include: (1) Can the current decline in the neonatal mortality rate continue? (2) Which infants not now surviving are potentially able to be saved? (3) What types of new programs may further reduce the neonatal mortality rate? (4) For which infants may research provide technology leading to further reductions in the neonatal mortality rate? In this analysis, birth weight-specific neonatal mortality rates for Alabama were compared with the lowest birth rate-specific neonatal mortality rates achieved in perinatal centers. Specific causes of neonatal death for each birth weight group were determined. Data suggest that 20% of current neonatal deaths would be preventable with available technology through expanded regionalization of perinatal care for infants born weighing less than 2,500 gm. Since lethal congenital anomalies cause the majority of neonatal deaths in infants born weighing greater than 2,499 gm, there is apparently little room for an improved neonatal mortality rate in this group. Without successful research leading to a reduction in preterm delivery rates, a reduction in lethal congenital anomalies or better survival of low-birth weight infants. Alabama's neonatal mortality rate is likely to level off at five to six per 1,000.

Alabama↗

Neurodevelopment of neonates in neonatal intensive care units and growth of surviving infants at age 2 years.

SUMMARY: The presence of development disorders in neonates attended in a Neonatal Intensive Care Unit (NICU) is highly variable; the aim of this study, therefore, was to determine the evolution of somatic and neurosensory development in a group of neonates requiring treatment in the NICU and to analyse the perinatal and developmental aspects of children presenting abnormalities. PATIENTS AND METHODS: A total of 492 neonates (275 premature, 106 with birthweight < or =1500 g), who were treated in the NICU between January 1994 and December 1997, were followed-up until the age of 2 years. Data were obtained concerning birthweight, body length, head circumference, gestational age, normality of weight for gestational age, single/multiple birth, duration of stay in the NICU and the hospital, duration of mechanically assisted respiration and evolutive somatometry, neurological examination and the Brunet-Lezine development test, adjusted for the gestational age of the neonates, at 6, 12, 18 and 24 months. When abnormal results were detected, Early Attention (EA) programmes were applied. RESULTS: Somatometry at birth in relation to gestational age revealed a weekly weight gain of 8.6%, an increase in body length of 1% and in head circumference of 1% (p<0.001). The evolution of somatic development to the age of 2 years showed that neonates with a birthweight < or =1500 g did not reach the values of neonates with a greater birthweight. The prevalence of cerebral palsy among all neonates was 6.8%, 14.6% among those weighing < or =1500 g, 4% among those weighing 1501-2500 g and 5% among those weighing >2500 g. The overall rate of neurosensory injury was 10.5%. These neonates presented less somatic development than those did with no neurologic disorder. To sum up, most of the neonates attended in the NICU during the 1990s presented a normal pattern of development. Nevertheless, they should be the object of special attention during the first years of life, particularly those neonates with a birthweight < or =1500 g and those presenting neurosensory risk.

Birth Weight↗

Ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit.

OBJECTIVE: To evaluate the frequency and clinical correlates of ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Massachusetts General Hospital and Mount Auburn Hospital. PATIENTS: A total of 117 patients (84 neonatal ICU patients and 33 normal newborns) studied over a 2-yr period of time. MEASUREMENTS: Blood samples were collected during the first 48 hrs after admission. The concentrations of magnesium (total and ultrafilterable), ionized calcium, parathyroid hormone, electrolytes, glucose and arterial blood gases were determined. RESULTS: Ultrafilterable circulating magnesium concentrations were determined in 74 of 84 neonatal ICU patients. On admission to the neonatal ICU, 23 (31.1%) of 74 neonates had ultrafilterable hypomagnesemia; two (2.7%) of 74 patients had ultrafilterable hypermagnesemia. Neonatal ICU patients had significantly lower (p < .001) ultrafilterable magnesium concentrations compared with normal neonates. Hypomagnesemic ICU patients required mechanical ventilatory support more frequently than did normomagnesemic ICU neonates (p < .05). Ionized hypocalcemia was a common finding in our patients (34 [42%] of 81). However, ultrafilterable hypomagnesemia was not statistically associated with ionized hypocalcemia (p > .05). Despite the below normal serum concentrations of ultrafilterable magnesium observed in our study, there was no impairment in parathyroid hormone secretion. CONCLUSIONS: Ultrafilterable hypomagnesemia is a common finding in neonates admitted to the ICU. Ultrafilterable hypomagnesemia is associated with the need for mechanical ventilation. To our knowledge, this is the first report of ultrafilterable magnesium concentrations in normal and sick neonates.

Bias↗

Skin colonization by Malassezia species in neonates: a prospective study and relationship with neonatal cephalic pustulosis.

OBJECTIVES: To assess skin colonization by Malassezia species in full-term healthy newborns, to investigate factors associated with colonization, and to look at acnelike cephalic pustulosis associated with this carriage. DESIGN: Samples were obtained from neonates and their mothers 0 to 5 days after birth and again 3 weeks later. Clinical patterns of common acnelike pustulosis were reported as mild (<10 papulopustules), moderate (> or =10 papulopustules), or absent. Direct examination and culture of sample. Identification of yeasts was based on microscopic and physiologic criteria. SETTING: A maternity hospital and the pediatric dermatology unit of a university hospital. PARTICIPANTS: Consecutive series of 102 neonates and their mothers. MAIN OUTCOME MEASURES: Incidence of skin colonization and type of Malassezia species found in neonates and correlation with neonatal cephalic pustulosis (neonatal acne). RESULTS: At the first visit, 11 neonates and 36 mothers had cultures positive for Malassezia. Malassezia sympodialis and Malassezia globosa were preferentially cultured. At 3 weeks, 29 (52%) of 56 neonates and 18 (32%) of 56 mothers had cultures positive for only M sympodialis and M globosa. Breastfeeding was not associated with a higher prevalence of Malassezia carriage in neonates. Malassezia colonization was higher when pustulosis was more severe and M sympodialis was found in pustules. CONCLUSIONS: Malassezia colonization begins at birth and increases in the first weeks of life. A high prevalence of M sympodialis in neonates is noted from birth. Its association with neonatal acne is confirmed. Further investigation is needed to study the role of sebum secretion rate and quality in the neonatal period.

Acne Vulgaris↗

Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: Early-onset sepsis (occurring within 72 hours of birth) is included in the differential diagnosis of most very low birth weight (VLBW) neonates. To determine the current incidence of early-onset sepsis, risk factors for disease, and the impact of early-onset sepsis on subsequent hospital course, we studied a cohort of 7861 VLBW neonates (401 to 1500 gm) admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991-1993). METHODS: The NICHD Neonatal Research Network maintains a prospectively collected registry on all VLBW neonates born or cared for at participating centers. Data from this registry were analyzed retrospectively. RESULTS: Blood culture-proven early-onset sepsis was uncommon, occurring in only 1.9% of VLBW neonates. Group B streptococcus was the most frequent pathogen associated with early-onset sepsis (31%), followed by Escherichia coli (16%) and Haemophilus influenzae (12%). Decreasing gestational age was associated with increased rates of infection. Antibiotic therapy for suspected sepsis is frequently initiated at birth in VLBW neonates. Almost half of the infants in this cohort were considered to have clinical sepsis and continued to receive antibiotics for 5 or more days, despite a negative blood culture result in 98% of cases. These findings underscore the difficulty of ruling out sepsis in the symptomatic immature neonate and the special concern for culture-negative clinical sepsis in the face of maternal antibiotic use. Neonates with early-onset sepsis were significantly more likely to have subsequent comorbidities, including severe intraventricular hemorrhage, patent ductus arteriosus, and prolonged assisted ventilation. Although 26% of VLBW neonates with early-onset sepsis died, only 4% of the 950 deaths that occurred in the first 72 hours of life were attributed to infection. For those infants discharged alive, early-onset sepsis was associated with a significantly prolonged hospital stay (86 vs 69 days; p <0.02). CONCLUSIONS: Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants. Improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected VLBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected.

Age of Onset↗

Reduced incidence of neonatal morbidities: effect of home-based neonatal care in rural Gadchiroli, India.

OBJECTIVE: We found a high burden of morbidities in a cohort of neonates observed in rural Gadchiroli, India. We hypothesised that interventions would reduce the incidence of neonatal morbidities, including the seasonal increase observed in many of them. This article reports the effect of home-based neonatal care on neonatal morbidities in the intervention arm of the field trial by comparing the early vs late periods, and the possible explanation for this effect. METHODS: During 3 years (1995 to 1998), trained village-health-workers (VHWs) in 39 villages prospectively collected data by making home visits during pregnancy, home-delivery and during neonatal period. We estimated the incidence and burden of neonatal morbidities over the 3 years from these data. In the first year, the VHWs made home visits only to observe. From the second year, they assisted mothers in neonatal care and managed the sick neonates at home. Health education of mothers and family members, individually and in group, was added in the third year. We measured the coverage of interventions over the 3 years and evaluated maternal knowledge and practices on 21 indicators in the third year. The effect on 17 morbidities was estimated by comparing the incidence in the first year with the third year. RESULTS: The VHWs observed 763 neonates in the first year, 685 in the second and 913 in the third year. The change in the percent incidence of morbidities was (i) infections, from 61.6 to 27.5 (-55%; p<0.001), (ii) care-related morbidities (asphyxia, hypothermia, feeding problems) from 48.2 to 26.3 (-45%; p<0.001); (iii) low birth weight from 41.9 to 35.2 (-16%; p<0.05); (iv) preterm birth and congenital anomalies remained unchanged. The mean number of morbidities/100 neonates in the 3 years was 228, 170 and 115 (a reduction of 49.6%; p<0.001). These reductions accompanied an increasing percent score of interventions during 3 years: 37.9, 58.4 and 81.3, thus showing a dose-response relationship. In the third year, the proportion of correct maternal knowledge was 78.7% and behaviours was 69.7%. The significant seasonal increase earlier observed in the incidence of five morbidities reduced in the third year. CONCLUSION: The home-based care and health education reduced the incidence and burden of neonatal morbidities by nearly half. The effect was broad, but was especially pronounced on infections, care-related morbidities and on the seasonal increase in morbidities.

Breast Feeding↗

Neonatal interleukin-12 capacity is associated with variations in allergen-specific immune responses in the neonatal and postnatal periods.

BACKGROUND AND OBJECTIVES: A reduced capacity of antigen presenting cells (APC) to provide pro-T helper 1 (Th1) signals, such as IL-12, to T cells during early life may be implicated in the development of T helper 2 (Th2)-mediated allergic disease. In this study we examined the relationships between the capacity for IL-12 responses in the neonatal period and atopic risk (family allergy), in vitro T cell responses to allergens, and the subsequent development of allergic disease at 6 years. METHODS: The capacity of circulating neonatal (and maternal) APC to produce IL-12 p70 in response to LPS (and IFN-gamma) stimulation was assessed in a group of 60 children with previously well-characterized immune responses to allergens and atopic outcomes. The IL-12 responses were compared with allergen-induced lymphoproliferation (to house dust mite (HDM) ovalbumin (OVA), cat and beta-lactoglobulin (BLG)) and IL-13 and IFN-gamma cytokine responses (to OVA, HDM and phytohaemaglutinin (PHA)) in the neonatal and postnatal periods. IL-12 responses were also compared according to atopic risk and atopic outcomes (doctor-diagnosed asthma, eczema, food allergies and sensitization as evidenced by skin prick testing) at 6 years clinical follow-up. RESULTS: Maternal peripheral blood mononuclear cells (PBMC) synthesized significantly greater amounts of IL-12 than neonatal PBMC, though within maternal-infant pairs IL-12 responses were significantly correlated (r = 0.4, P = 0.019). Moreover, neonatal IL-12 responses were positively correlated with neonatal allergen proliferation for HDM (r = 0.6, P < 0.0001), OVA (r = 0.55, P < 0.0001), cat (r = 0.5, P = 0.003) and BLG (r = 0.55, P = 0.001), but negatively correlated with neonatal IL-13 responses to both allergens tested (HDM: r = - 0.4, P = 0.03 and OVA: r = - 0.5, P = 0.001). Both neonatal and maternal IL-12 responses were positively correlated with postnatal IFN-gamma responses to HDM at 12, 18 and 24 months of age (responses after age of 2 years were not assessed). There was no relationship between atopic risk and IL-12 capacity in the neonatal period, but there was a (non-significant) trend for neonatal IL-12 responses to be lower in the high-risk children who developed clinical allergy at 6 years (compared with the low risk group) although the number in this analysis was small. CONCLUSIONS: Reduced APC IL-12 production in the perinatal period was associated with reduced T cell activation (lymphoproliferation), stronger neonatal Th2 responses, and weaker Th1 responses to allergen in the postnatal period. This supports the notion that variations in APC function in early life may contribute to altered allergen-specific cytokine responses associated with later allergy.

Allergens↗

The generation of Th memory in neonates versus adults: prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates.

Immunization during the neonatal period often results in Th2-biased secondary responses. To understand the regulation of this phenomenon, we have examined all phases of Th development, from the generation of primary effectors to the duration of the primary effector stage to the production of memory effector function. First, we had previously reported that although primary responses in the neonatal lymph nodes are mature, mixed Th1/Th2-like, primary responses in the spleens of the same animals are exclusively Th2-like. To determine whether Th2-dominant secondary responses are due to the Th2-polarized primary function in the spleen, neonates were splenectomized before immunization. Even in the absence of primary neonatal splenic responses, the secondary responses of neonates were Th2 dominant. Thus, the overwhelmingly Th2 primary responses in the neonatal spleen are not required to generate Th2-dominant memory in the lymph nodes. Second, we have compared the kinetics of the primary response phase in neonates and adults. In adults, Ag-specific Th2 function disappeared rapidly from both the lymph nodes and spleen. In contrast, primary Th2 function persisted out to 5 wk in both neonatal organs. Third, the generation of Th memory responses was examined in animals initially immunized as neonates and in adults. These experiments demonstrated that neonates are selectively impaired in the development of Th1 memory effector function. Together, these results indicate that neonates are biased to Th2 function at all phases of an immune response.

Adjuvants, Immunologic↗

Risk factors for neonatal mortality: Harare Central Hospital Neonatal Unit--Zimbabwe.

OBJECTIVE: To assess risk factors for neonatal mortality in a tertiary level neonatal unit. DESIGN: Case control analysis of routine neonatal data for 1998. SETTING: Harare Central Hospital Neonatal Unit. SUBJECTS: All neonates delivered at Harare Maternity Hospital and admitted to the neonatal unit for care between January and December 1998. MAIN OUTCOME MEASURE: Neonatal mortality in hospital. RESULTS: A total of 5,305 neonatal admissions were studied of which 19.3% died in hospital. The median age at death was two days (Q1 = 1, Q3 = 3) and the median age at hospital discharge was 3 days (Q1 = 1, Q3 = 6). Risk factors for mortality were un-booked mother odds ratio (OR) 2.36 (95% CI = 1.98 to 2.81), breech delivery OR: 1.76 (95% CI = 1.39 to 2.22), low birth weight OR: 4.67 (95% CI = 3.92 to 5.57), prematurity OR: 2.36 (95% CI = 2.09 to 2.66), congenital malformations OR: 2.80 (95% CI = 1.72 to 4.53) and birth asphyxia OR: 1.79 (95% CI = 1.51-2.12). Being admitted for respiratory distress was associated with better survival OR: 0.22 (95% CI = 0.17 to 0.28). Having a Caesarian section was also protective OR: 0.60 (95% CI = 0.47 to 0.76). Mother's age, parity, time of delivery and sex were not significantly associated with mortality odds ratios (95% CI) of 1.07 (0.86 to 1.34), 0.94 (0.78 to 1.13), 1.10 (0.93 to 1.30) and 0.89 (0.78 to 1.03) respectively. On regression analysis birth weight greater than 2,500 g, being un booked and breech delivery were predictive of mortality with OR (95% CI) of 0.99 (0.99 to 0.99), 1.31 (1.12 to 1.61) and 1.15 (1.04 to 1.28) respectively. CONCLUSION: Low birth weight is the highest risk factor for mortality in this tertiary level hospital. Strategies targeted at low birth weight infants such as antenatal corticosteroid use, improved intrapartum care, appropriate antibiotic use, improved efficiency and access to neonatal intensive care will have the most impact on neonatal mortality.

Adolescent↗

Controlled trial of universal neonatal screening for early identification of permanent childhood hearing impairment. Wessex Universal Neonatal Hearing Screening Trial Group.

BACKGROUND: Congenital permanent childhood hearing impairment (PCHI) impairs communication skills and, possibly, mental health and employment prospects. Management within 1 year of birth can alleviate most of its adverse effects. Neonatal screening for this disorder is feasible but its benefit for all babies is disputed. We investigated whether neonatal screening of all babies born in hospital, in addition to the standard health visitor distraction test, would increase the rates of early referral, confirmation, and management. METHODS: Between 1993 and 1996, two teams of four part-time testers and equipment moved between two pairs of hospitals to achieve four periods with neonatal screening and four without neonatal screening, each of 4-6 months' duration. Babies did or did not undergo neonatal screening dependent on during which periods they were born. We used a transient evoked otoacoustic emissions test and, in babies who failed this test, an automated auditory brainstem response test on the same day. We referred babies with positive results for audiological assessment. FINDINGS: 53,781 babies were included in the trial, and 25,609 were born during periods with neonatal screening. Neonatal screening achieved 87% coverage of births, with a false-alarm rate of 1.5%, and an overall yield of 90 cases of bilateral PCHI of 40 dB or more relative to hearing threshold level per 100,000 target population, equivalent to 80% of the expected prevalence of the disorder in the population. 71 more babies with moderate or severe PCHI per 100,000 target population were referred before age 6 months during periods with neonatal screening than during periods without. Early confirmation and management of PCHI were significantly increased. The rate of false-negative results from neonatal screening was significantly lower than that for the distraction test (4 vs 27% p=0.041). INTERPRETATION: Neonatal screening is effective in identification of congenital PCHI early and may be particularly useful for babies with moderate and severe PCHI for whom early management may have the most benefit.

England↗

Neonatal neutrophil host defense. Prospects for immunologic enhancement during neonatal sepsis.

Neonatal host defense simulates a clinical state of immunodeficiency that predisposes the preterm and term newborn to overwhelming bacterial sepsis. There are various immunologic components that are deficient in the newborn and new methods to enhance their function. Defects in both the quantitative and qualitative aspects of the neonatal phagocyte contribute substantially to the immaturity of neonates' immune systems. The neonate lacks an adequate number of granulocyte bone marrow progenitor cells, and has a decreased neutrophil storage pool and an increased tendency to peripheral neutropenia during neonatal sepsis. Additionally, the neonatal granulocyte demonstrates altered physiologic function compared with that found in the adult with respect to chemotaxis, phagocytosis, oxidative metabolism, and bacterial killing. Some recent clinical studies have suggested the benefit of using adult neutrophil transfusions as adjuvant treatment during neonatal bacterial sepsis, yet other studies have found the use of polymorphonuclear neutrophil leukocyte transfusions to be inconclusive. Reduced circulating immunoglobulins and impaired production of specific antibody have also led to recent trials in the use of prophylactic intravenous immunoglobulin in preterm infants predisposed to sepsis. Recently, hematopoietic colony-stimulating factors have been demonstrated to improve in vitro neonatal neutrophil physiologic activity. Future therapy of neonatal sepsis will depend on new nontoxic methods for enhancing neonatal host defense.

Blood Transfusion↗

4-Aminobiphenyl induces liver DNA adducts in both neonatal and adult mice but induces liver mutations only in neonatal mice.

The mechanisms underlying the susceptibility of neonatal mice to genotoxic carcinogens were investigated by analyzing the DNA adducts and mutations induced in the livers of neonatal and adult Big Blue transgenic mice by 4-aminobiphenyl (4-ABP), a potent human and rodent carcinogen. Neonatal and adult mice were treated with a regimen of 4-ABP known to induce tumors in neonatal mice. Animals were sacrificed 1 day after the last treatment for DNA adduct analysis and 8 weeks after the last treatment for analysis of lacI and cII mutant frequency (MF). N-(Deoxyguanosin-8-yl)-4-ABP was the major DNA adduct identified in the livers of the 4-ABP-treated mice and levels of this adduct were significantly higher in treated animals than in the controls for both the neonates and adults. Adduct levels for adult females (44.0 +/- 4.8 adducts/10(6) nucleotides) were higher than in neonatal females (25.9 +/- 2.2 adducts/10(6) nucleotides), while adduct levels in adult males (13.5 +/- 2.0 adducts/10(6) nucleotides) were lower than in neonatal males (33.8 +/- 4.1 adducts/10(6) nucleotides). 4-ABP treatment significantly increased the liver cII MFs in both sexes of neonatal mice but not in adult mice. Sequence analysis of cII mutant DNA revealed that 4-ABP induced a unique spectrum of mutations in neonatal mice, characterized by a high frequency of G:C-->T:A transversion, while the mutation spectrum in 4-ABP-treated adults was similar to that of control mice. Our results indicate that DNA adduct formation by 4-ABP depends as much on sex as it does on age, whereas the conversion of DNA adducts into mutations differed with animal age. These observations suggest that neonates are more sensitive than adults to genotoxic carcinogens because the relatively high levels of cell division in the developing animal facilitate the conversion of DNA damage into mutation. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html

Aging↗

Predictors of neonatal resuscitation, low Apgar scores, and umbilical artery pH among growth-restricted neonates.

OBJECTIVE: To identify risk factors associated with poorer immediate neonatal outcomes among growth-restricted neonates. METHODS: Records of all 530 growth-restricted neonates born between January 1989 and February 1995 were reviewed. Outcomes included resuscitation measures, Apgar scores, and umbilical blood gas values. Neonates were assigned to one of six anesthetic groups, and outcomes were compared. Predictors of poorer outcomes were examined using logistic and linear regression. RESULTS: Neonates exposed to general anesthesia were more likely to be intubated (37.9% versus 4.1%, P < .001, Pearson chi2) and had lower mean 1- (4.0 versus 7.0) and 5-minute (6.5 versus 8.4) Apgar scores (P < .01, Scheffé) than those in all other anesthetic groups. They also had significantly lower umbilical artery (UA) pH values than neonates who received nalbuphine, epidural, or no anesthesia (7.21 versus 7.28, 7.26, 7.29, respectively; P < .01, Scheffé). Factors that significantly and independently predicted intubation among all neonates included exposure to general anesthesia (odds ratio [OR] 4.1; 95% confidence interval [CI] 1.9, 8.9) and lower infant weight (OR 10.1 per kg decrease; CI 5.1, 20). Factors predicting UA pH at most 7.15 included preeclampsia (OR 3.0; CI 1.5, 5.9) and older maternal age (OR 1.3 per 5 years; CI 1.02, 1.64); vertex delivery (OR 0.5; CI 0.2, 0.9) was protective. Factors predicting a 5-minute Apgar less than 7 were meconium (OR 1.5 per category going from none to terminal to light to heavy; CI 1.04, 2.3), general anesthesia (OR 6.9; CI 2.6, 18.2), lower infant weight (OR 16.5 per kg decrease; CI 7.8, 34.5), and vaginal breech delivery (OR 7.0; CI 1.8, 28.6); cesarean delivery (OR 0.2; CI 0.08, 0.66) was protective. Spontaneous vertex delivery raised the UA pH, and preeclampsia, amnioinfusion, breech delivery, and general anesthesia significantly and independently lowered the UA pH among all neonates. For infants delivered by cesarean, "fetal distress," preeclampsia, previous spontaneous abortion, failed forceps use, and nalbuphine significantly and independently predicted lower UA pH. CONCLUSION: Risk factors for poorer immediate neonatal outcomes among growth-restricted neonates include preeclampsia, fetal distress, breech delivery, forceps use, nalbuphine during labor, lower infant weight, and general anesthesia.

Analgesics, Opioid↗

Maternal, neonatal and community factors influencing neonatal mortality in Brazil.

Child mortality (the mortality of children less than five years old) declined considerably in the developing world in the 1990s, but infant mortality declined less. The reductions in neonatal mortality were not impressive and, as a consequence, there is an increasing percentage of infant deaths in the neonatal period. Any further reduction in child mortality, therefore, requires an understanding of the determinants of neonatal mortality. 209,628 birth and 2581 neonatal death records for the 1998 birth cohort from the city of São Paulo, Brazil, were probabilistically matched. Data were from SINASC and SIM, Information Systems on Live Births and Deaths of Brazil. Logistic regression was used to find the association between neonatal mortality and the following risk factors: birth weight, gestational age, Apgar scores at 1 and 5 minutes, delivery mode, plurality, sex, maternal education, maternal age, number of prior losses, prenatal care, race, parity and community development. Infants of older mothers were less likely to die in the neonatal period. Caesarean delivery was not found to be associated with neonatal mortality. Low birth weight, pre-term birth and low Apgar scores were associated with neonatal death. Having a mother who lives in the highest developed community decreased the odds of neonatal death, suggesting that factors not measured in this study are behind such association. This result may also indicate that other factors over and above biological and more proximate factors could affect neonatal death.

Adolescent↗