Abstracts en Pediatrics

Diciembre 2006

 

 

Abstracts en Journal Pediatrics Diciembre  2006 relacionados con Neonatología

 

December 2006 | Volume 118 | Issue 6

 

 

Abstract 1 of 13  

 

Herpes Simplex Virus Infections in Preterm Infants

 

Declan P. O'Riordan, MD y Cols.

 

OBJECTIVE. Neonatal herpes simplex virus infections cause significant neonatal mortality and morbidity, but the course and prognosis in preterm infants is not well documented. We performed a retrospective review of herpes simplex virus infections at out institution within the first 30 days after birth in infants who were born at <37 weeks to help better define the symptoms and signs of herpes simplex virus infections in preterm infants and to assist in prognosis.

METHODS. Hospital databases were reviewed to identify culture- or polymerase chain reaction–proven cases of herpes simplex virus-1 or herpes simplex virus-2 infections that occurred in preterm newborns between 1989 and 2003. Maternal and neonatal histories, clinical features, and laboratory results were reviewed systematically.

RESULTS. Ten preterm singletons and a set of twins were infected with herpes simplex virus-2 during the first month after birth. No mother had herpes simplex virus lesions at delivery, but a history of genital herpes simplex or other sexually transmitted infections was prevalent among the mothers. Infants presented with either disseminated disease or encephalitis. All infants with disseminated disease (n = 9) died, whereas the 3 infants with encephalitis survived. All infants in the cohort developed respiratory distress, and consistent with the prominence of respiratory symptoms, viral cultures of the respiratory tract were consistently positive. Ten of 12 infants received acyclovir, but despite treatment within 48 hours of symptoms, infants with disseminated disease deteriorated rapidly and died. Two of 3 infants who received high-dosage (60 mg/kg per day) acyclovir survived.

CONCLUSIONS. Herpes simplex virus infections in preterm infants usually present during the first 2 weeks of life with respiratory distress and a high incidence of disseminated disease. Viral respiratory cultures have a high yield for documentation of infection. The morbidity of herpes simplex virus in this population may be attributable to a relatively immature immune system in this population. Additional studies are necessary to delineate the evolution of herpes simplex virus disease in preterm infants and the role of antiviral therapy in mitigating the sequelae of herpes simplex virus infections in this population.

 

 

Abstract 2 of 13 

 

Increasing Prevalence of Cerebral Palsy Among Very Preterm Infants: A Population-Based Study

 

Michael J. Vincer, MD y Cols.  

 

OBJECTIVES. It is unclear whether declines in neonatal and infant mortality have led to changes in the occurrence of cerebral palsy. We conducted a study to examine and investigate recent temporal changes in the prevalence of cerebral palsy in a population-based cohort of very preterm infants who were 24 to 30 weeks of gestational age.

METHODS. A population-based cohort of very preterm infants who were born between January 1, 1993, and December 31, 2002, was evaluated by the Perinatal Follow-up Program of Nova Scotia. Follow-up extended to age 2 years to ascertain the presence or absence of cerebral palsy and for overall survival. Infant survival and cerebral palsy rates were compared by year and also in two 5-year periods, 1993–1997 and 1998–2002. Logistic regression analyses were used to identify factors that potentially were responsible for temporal changes in cerebral palsy rates.

RESULTS. A total of 672 liveborn very preterm infants were born to mothers who resided in Nova Scotia between 1993 and 2002. Infant mortality among very preterm infants decreased from 256 per 1000 live births in 1993 to 114 per 1000 live births in 2002, whereas the cerebral palsy rates increased from 44.4 per 1000 live births in 1993 to 100.0 per 1000 live births in 2002. Low gestational age, postnatal dexamethasone use, patent ductus arteriosus, severe hyaline membrane disease, resuscitation in the delivery room, and intraventricular hemorrhage were associated with higher rates of cerebral palsy, whereas antenatal corticosteroid use was associated with a lower rate.

CONCLUSION. Cerebral palsy has increased substantially among very preterm infants in association with and possibly as a consequence of large declines in infant mortality.

 

 

Abstract 3 of 13 

 

Vitamin K Prophylaxis for Preterm Infants: A Randomized, Controlled Trial of 3 Regimens

 

Paul Clarke, MB  y Cols.

 

OBJECTIVE. Preterm infants may be at particular risk from either inadequate or excessive vitamin K prophylaxis. Our goal was to assess vitamin K status and metabolism in preterm infants after 3 regimens of prophylaxis.

METHODS. Infants <32 weeks’ gestation were randomized to receive 0.5 mg (control) or 0.2 mg of vitamin K1 intramuscularly or 0.2 mg intravenously after delivery. Primary outcome measures were serum vitamin K1, its epoxide metabolite (vitamin K1 2,3-epoxide), and undercarboxylated prothrombin assessed at birth, 5 days, and after 2 weeks of full enteral feeds. Secondary outcome measures included prothrombin time and factor II concentrations.

RESULTS. On day 5, serum vitamin K1 concentrations in the 3 groups ranged widely (2.9–388.0 ng/mL) but were consistently higher than the adult range (0.15–1.55 ng/mL). Presence of vitamin K1 2,3-epoxide on day 5 was strongly associated with higher vitamin K1 bolus doses. Vitamin K1 2,3-epoxide was detected in 7 of 29 and 4 of 29 infants from the groups that received 0.5 mg intramuscularly and 0.2 mg intravenously, respectively, but in none of 32 infants from group that received 0.2 mg intramuscularly. After 2 weeks of full enteral feeding, serum vitamin K1 was lower in the infants who received 0.2 mg intravenously compared with the infants in the control group. Three infants from the 0.2-mg groups had undetectable serum vitamin K1 as early as the third postnatal week but without any evidence of even mild functional deficiency, as shown by their normal undercarboxylated prothrombin concentrations.

CONCLUSIONS. Vitamin K1 prophylaxis with 0.2 mg administered intramuscularly maintained adequate vitamin K status of preterm infants until a median age of 25 postnatal days and did not cause early vitamin K1 2,3-epoxide accumulation. In contrast, 0.2 mg administered intravenously and 0.5 mg administered intramuscularly led to vitamin K1 2,3-epoxide accumulation, possibly indicating overload of the immature liver. To protect against late vitamin K1 deficiency bleeding, breastfed preterm infants given a 0.2-mg dose of prophylaxis should receive additional supplementation when feeding has been established.

 

 

Abstract 4 of 13

 

Effect of Opening Midlevel Neonatal Intensive Care Units on the Location of Low Birth Weight Births in California

 

Corinna A. Haberland, MD y Cols.

 

OBJECTIVE. Despite evidence and recommendations encouraging the delivery of high-risk newborns in hospitals with subspecialty or high-level NICUs, increasing numbers are being delivered in other facilities. Causes for this are unknown. We sought to explore the impact of diffusion of specialty or midlevel NICUs on the types of hospitals in which low birth weight newborns are born.

DESIGN. We used birth certificate, death certificate, and hospital discharge data for essentially all low birth weight, singleton California newborns born between 1993 and 2000. We identified areas likely to have been affected by the opening of a new nearby midlevel unit, analyzed changes over time in the share of births that took place in midlevel NICU hospitals, and compared patterns in areas that were and were not likely affected by the opening of a new midlevel unit. We also tracked the corresponding changes in the share of births in high-level hospitals and in those without NICU facilities (low-level).

RESULTS. The probability of a 500- to 1499-g infant being born in a midlevel unit increased by 17 percentage points after the opening of a new nearby unit. More than three quarters of this increase was accounted for by reductions in the probability of birth in a hospital with a high-level unit (–15 points), and the other portion was resulting from reductions in the share of newborns delivered in hospitals with low-level centers (–2 points). Similar patterns were observed in 1500- to 2499-g newborns.

CONCLUSIONS. The introduction of new midlevel units was associated with significant shifts of births from both high-level and low-level hospitals to midlevel hospitals. In areas in which new midlevel units opened, the majority of the increase in midlevel deliveries was attributable to shifts from high-level unit births. Continued proliferation of midlevel units should be carefully assessed.

 

 

Abstract 5 of 13 

 

Accuracy of the Diagnosis of Physical Features of Fetal Alcohol Syndrome by Pediatricians After Specialized Training

 

Kenneth Lyons Jones, MD y Cols.

 

OBJECTIVES. Accurate and early diagnosis of the fetal alcohol syndrome is important for secondary prevention, intervention, and treatment, yet many pediatricians lack expertise in recognition of the characteristic features of this disorder. After a structured training program for pediatricians, we examined the ability to accurately diagnose fetal alcohol syndrome.

METHODS. Two dysmorphologists conducted a 2-day training program in the diagnosis of the physical features of fetal alcohol syndrome for 4 pediatricians in Moscow. Dysmorphologists and pediatricians worked in teams to examine children, demonstrate techniques, and validate that pediatricians could identify physical features of this disorder under direct observation. Subsequently, pediatricians independently evaluated children in 41 boarding schools and orphanages. Those children diagnosed with fetal alcohol syndrome or deferred (possible fetal alcohol syndrome) by the pediatricians were then evaluated by the dysmorphologists. Accuracy of the diagnosis of fetal alcohol syndrome or deferred was assessed, as well as the interrater agreement for specific selected features of the disorder.

RESULTS. A total of 110 children were examined by both the pediatricians and the dysmorphologists. Of these, 79 were identified with fetal alcohol syndrome by the pediatricians; in 66 (83.5%) of these children, the diagnosis was confirmed by the dysmorphologists. Among 31 children who were classified as deferred by the pediatricians, 21 (67.7%) were confirmed with either fetal alcohol syndrome or deferred by the dysmorphologists. With respect to selected structural features characteristic of fetal alcohol syndrome, good interrater agreement was noted for height and head circumference ≤10th centile, whereas moderate-to-fair agreement was noted for smooth philtrum, long philtrum, presence of "hockey-stick" palmar crease, and palpebral fissure length ≤10th centile. Poor agreement was noted for thin upper lip.

CONCLUSIONS. After a relatively short training session, pediatricians were reasonably accurate in diagnosing fetal alcohol syndrome on the basis of physical features and in recognizing most of the selected specific features associated with the disorder.

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    Abstract 6 of 13  

     

    The Development and Testing of a Performance Checklist to Assess Neonatal Resuscitation Megacode Skill

     

    Jocelyn Lockyer, PhD y Cols.

     

    PURPOSE. The purpose of this work was to develop and assess the feasibility, reliability, and validity of a brief performance checklist to evaluate skills during a simulated neonatal resuscitation ("megacode") for the Neonatal Resuscitation Program of the American Academy of Pediatrics.

    METHODS. A performance checklist of items was created, validated, and modified in sequential phases involving: an expert committee, review, and feedback by Neonatal Resuscitation Program instructors for feasibility and criticality and use of the performance checklist by Neonatal Resuscitation Program instructors reviewing videotaped megacodes. The final 20-item performance checklist used a 3-point scale and was assessed by student and instructor volunteers. Megacode scores, the NRP multiple-choice examination scores, student assessments of their ability and performance, and sociodemographic descriptors for both students and instructors were collected. Data were analyzed descriptively. In addition, we assessed the megacode score internal consistency reliability, the correlations between megacode and multiple-choice examination scores, and the variance in scores based on instructor and student characteristics.

    RESULTS. A total of 468 students and 148 instructors volunteered for the study. The instrument was reliable and internally consistent. Student's scores were high on most items. There was a significant but low correlation between the megacode score and the written knowledge examination. Instructor and student characteristics had little effect on the variance in scores.

    CONCLUSIONS. This performance checklist provides a feasible assessment tool. There is evidence for its reliability and validity.

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    Abstract 7 of 13 

     

    Earlier Apgar Score Increase in Severely Depressed Term Infants Cared for in Swedish Level III Units With 40% Oxygen Versus 100% Oxygen Resuscitation Strategies: A Population-Based Register Study

     

    Lena Hellström-Westas, MD y Cols.

     

    OBJECTIVES. The aim of this study was to evaluate whether a resuscitation strategy based on administration of 40% oxygen influences mortality rates and rates of improvement in 5-minute Apgar scores, compared with a strategy based on 100% oxygen administration.

    METHODS. A population-based study evaluated data from 4 Swedish perinatal level III centers during the period of 1998 to 2003. During this period, the centers used either of 2 resuscitation strategies (initial oxygen administration of 40% or 100%). Live-born, singleton, term infants with 1-minute Apgar scores of <4, with a birth weight appropriate for gestational age, and without major malformations were included in the study (n = 1223).

    RESULTS. Infants born in hospitals using a 40% oxygen strategy had a more rapid Apgar score increase than did infants born in hospitals using a 100% oxygen strategy; however, no difference remained at 10 minutes. The mean Apgar score increased from 2.01 at 1 minute to 6.74 at 5 minutes in the 2 hospitals initiating resuscitation with 40% oxygen, compared with 2.01 to 6.38 in the 2 hospitals using 100% oxygen, with a mean difference in Apgar score increases of 0.36. At 5 minutes, 44.3% of infants born in the hospitals using 100% oxygen had an Apgar score of <7, compared with 34.0% of infants at the hospitals using 40% oxygen. At 10 minutes, the mean Apgar scores were 8.16 at the hospitals using 40% oxygen and 8.07 at the hospitals using 100% oxygen. There were no significant differences in rates of neonatal death, hypoxic ischemic encephalopathy, or seizures in relation to the 2 oxygen strategies.

    CONCLUSION. Severely depressed term infants born in hospitals initiating resuscitation with 40% oxygen had earlier Apgar score recovery than did infants born in hospitals using a 100% oxygen strategy.

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    Abstract 8 of 13 

     

    Magnetic Resonance Imaging of Neonatal Encephalopathy at 4.7 Tesla: Initial Experiences

     

    Enrico De Vita, PhD y Cols.

     

    OBJECTIVES. The goals were to develop safe 4.7-T MRI examination protocols for newborn infants and to explore the advantages of this field strength in neonatal encephalopathy.

    METHODS. Nine ventilated newborn infants with moderate or severe encephalopathy were studied at 4.7 T, with ethical approval and informed parental consent. The custom-made, 4.7-T-compatible, neonatal patient management system included acoustic noise protection and physiologic monitoring. An adult head coil was used. Acquisition parameters for T2-weighted fast spin echo MRI and a variety of T1-weighted methods were adapted for MRI of neonatal brain at 4.7 T. The pulse sequences used had a radiofrequency specific absorption rate of <2 W/kg.

    RESULTS. Physiologic measures were normal throughout each scan. T2-weighted fast spin echo imaging provided better anatomic resolution and gray/white matter contrast than typically obtained at 1.5 T; T1-weighted images were less impressive.

    CONCLUSIONS. With appropriate safety precautions, MRI of newborn infants undergoing intensive care is as feasible at 4.7 T as it is at 1.5 T; our initial studies produced T2-weighted fast spin echo images with more detail than commonly obtained at 1.5 T. Although T1-weighted images were not adequately informative, additional pulse sequence optimization may be advantageous. A smaller neonatal head coil should also permit greater flexibility in acquisition parameters and even more anatomic resolution and tissue contrast. In neonatal encephalopathy, interpretation of the T2-weighted pathologic detail in combination with comprehensive neurodevelopmental follow-up should improve prognostic accuracy and enable more patient-specific therapeutic interventions. In addition, more precise relationships between structural changes and functional impairment may be defined.

     

     

    Abstract 9 of 13 

     

    Survival Rates and Mode of Delivery for Vertex Preterm Neonates According to Small- or Appropriate-for-Gestational-Age Status

     

    Henry Chong Lee, MD y Cols.

     

    OBJECTIVE. The goal was to characterize the relationship between cesarean section delivery and death for preterm vertex neonates according to intrauterine growth.

    METHODS. Maternal and infant data from the National Center for Health Statistics for 1999 and 2000 were analyzed. Neonates with gestational ages of 26 to 36 weeks were characterized as small for gestational age (<10th percentile) or appropriate for gestational age (10th to 90th percentile). Mortality rates at 28 days and relative risks were calculated for each gestational age group according to mode of delivery.

    RESULTS. Cesarean section rates were higher for small-for-gestational-age neonates compared with appropriate-for-gestational-age neonates, most prominently from 26 weeks to 32 weeks of gestation, at which small-for-gestational-age neonates had cesarean section rates of 50% to 67%, whereas appropriate-for-gestational-age neonates had rates of 22% to 38%. Small-for-gestational-age neonates at gestational ages of <31 weeks had increased survival rates associated with cesarean section, whereas small-for-gestational-age neonates at >33 weeks and appropriate-for-gestational-age neonates overall had decreased survival rates associated with cesarean section. After adjustment for sociodemographic and medical factors, the survival advantage for small-for-gestational-age neonates at gestational ages of 26 to 30 weeks persisted.

    CONCLUSIONS. Cesarean section delivery was associated with survival for preterm small-for-gestational-age neonates but not preterm appropriate-for-gestational-age neonates. We speculate that vaginal delivery may be particularly stressful for small-for-gestational-age neonates. We found no evidence that prematurity alone is a valid indication for cesarean section for preterm appropriate-for-gestational-age neonates.

     

     

    Abstract 10 of 13 

     

    Preventable Newborn Readmissions Since Passage of the Newborns’ and Mothers’ Health Protection Act

     

    Ian M. Paul, MD y Cols. ,

     

    BACKGROUND. Congress passed the Newborns’ and Mothers’ Health Protection Act in 1996, reversing the trend of shorter newborn nursery lengths of stay. Hope existed that morbidities would lessen for this vulnerable population, but some reports indicate that the timeliness and quality of postdischarge care may have worsened in recent years.

    OBJECTIVE. Our goal was to determine risk factors for the potentially preventable readmissions because of jaundice, dehydration, or feeding difficulties in the first 10 days of life in Pennsylvania since passage of the Newborns’ and Mothers’ Health Protection Act.

    PATIENTS AND METHODS. Birth records from 407826 newborns ≥35 weeks’ gestation from 1998 to 2002 were merged with clinical discharge records. A total of 2540 newborns rehospitalized for jaundice, dehydration, or feeding difficulties in the first 10 days of life were then compared with 5080 control infants. Predictors of readmission were identified by using multiple logistic regression analysis.

    RESULTS. An unadjusted comparison of baseline characteristics revealed numerous predictors of readmission. Subsequent adjusted analysis revealed that Asian mothers, those 30 years of age or older, nonsmokers, and first-time mothers were more likely to have a readmitted newborn, as were those with diabetes and pregnancy-induced hypertension. For neonates, female gender and delivery via cesarean section were protective for readmission, whereas vacuum-assisted delivery, gestational age <37 weeks, and nursery length of stay <72 hours were predictors of readmission in the first 10 days of life.

    CONCLUSIONS. Although readmissions for jaundice, dehydration, and feeding difficulties may be less common for some minority groups and Medicaid recipients in the era of the Newborns’ and Mothers’ Health Protection Act compared with nonminorities or privately insured patients, several predictors of newborn readmission have established associations with inexperienced parenting and/or breastfeeding difficulty. This is one indication that this well-intentioned legislation and current practice may not be sufficiently protecting the health of newborns and suggests that additional support for mothers and newborns during the vulnerable postdelivery period may be indicated.

     

    Abstract 11 of 13 

     

    Risk Factors for Progression to Invasive Fungal Infection in Preterm Neonates With Fungal Colonization

     

    Paolo Manzoni, MD y Cols.

     

    OBJECTIVE. Colonization by Candida spp is a major risk factor for development of fungal sepsis, but little is known about the variables associated with progression to invasive disease in already colonized neonates. We investigated such variables in a large number of colonized preterm neonates in an NICU.

    SETTING. This study was conducted in the Department of Neonatology and the NICU at Sant'Anna Hospital in Torino, Italy.

    DESIGN AND PATIENTS A database search of clinical charts and weekly surveillance cultures was used to identify all neonates with birth weights <1500 g (very low birth weight) who were admitted to our NICU during 1998–2005 and were colonized (≥1 site) by Candida spp during their stay, as well as infants with invasive fungal infection. The association between a number of factors with progression to invasive fungal infection was evaluated. Those shown to be significantly associated by univariate analysis were cross-checked by logistic regression.

    RESULTS. Colonization occurred in 201 infants (32.1% of very low birth weight admitted neonates), and invasive fungal infection occurred in 51 (8.1%) of them, with an overall progression rate of 0.25. At univariate analysis, 10 factors (namely low birth weight, low gestational age, use of third-generation cephalosporins, endotracheal intubation, duration of stay in the NICU, bacterial sepsis, colonization of central venous catheter, of endotracheal tube, of gastric aspirate, or in ≥3 [multiple] sites) were associated with an increased risk of progression, whereas prophylaxis with fluconazole was associated to a decreased risk. After logistic regression, only colonization of central venous catheter and colonization in multiple sites remained significantly associated with invasive fungal infection. Fluconazole prophylaxis remained an independent protective factor.

    CONCLUSIONS. Central venous catheter colonization and multiple-site colonization are independent risk factors and predictors of progression to fungal sepsis in preterm very low birth weight neonates colonized by Candida spp during their stay in the NICU. Fluconazole prophylaxis is an independent protective factor. These findings can be used to improve the surveillance, prophylaxis, or preemptive measures in neonates at high risk.

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    Abstract 12 of 13 

     

    Direct Medical Costs of Bronchiolitis Hospitalizations in the United States

     

    Andrea J. Pelletier, MPH y Cols. 

     

    OBJECTIVES. Although bronchiolitis is the leading cause of hospitalization for infants, there are limited data describing the epidemiology of bronchiolitis hospitalizations, and the associated cost is unknown. Our objective was to determine nationally representative estimates of the frequency of bronchiolitis hospitalizations and its associated costs.

    PATIENTS AND METHODS. We analyzed the 2002 Health Care Utilization Project-National Inpatient Sample, a federal, stratified random survey of hospital discharges. For admissions age <2 years with a discharge diagnosis of bronchiolitis (International Classification of Diseases, Ninth Revision, Clinical Modification, code 466.1), we used nationally representative weighted estimates to determine frequency and total hospital charges. Costs were estimated from reported charges by applying hospital-specific cost/charge ratios based on all-payer inpatient cost.

    RESULTS. In 2002, an estimated 149000 patients were hospitalized with bronchiolitis. Frequency of hospitalizations was higher among children age <1 year of age, male gender, and nonwhite race. Mean length of stay was 3.3 days. Total annual costs for bronchiolitis-related hospitalizations were $543 million, with a mean cost of $3799 per hospitalization. Mean cost of bronchiolitis with a codiagnosis of pneumonia was $6191. In a multivariate analysis controlling for 3 confounding factors (including length of stay), cost per hospitalization was higher for children ³ 1 year and lower for those in the South versus Northeast.

    CONCLUSIONS. Bronchiolitis admissions cost more than $500 million annually. A codiagnosis of bronchiolitis and pneumonia almost doubles the cost of the hospitalization. Inpatient health care costs of bronchiolitis are higher than estimated previously and highlight the need for initiatives to safely reduce bronchiolitis hospitalizations and thereby decrease health care costs.

     

     

    Abstract 13 of 13 

     

    Alterations in Neurobehavior at Term Reflect Differing Perinatal Exposures in Very Preterm Infants

     

    Nisha C. Brown, BOT, PhD y Cols.

     

    OBJECTIVES. Preterm infants have higher rates of cognitive and behavioral difficulties at school age than their term-born peers. We hypothesized that neurobehavior at term would be different in very preterm infants compared with term infants and that perinatal exposures would be associated with these alterations in neurobehavior.

    PATIENTS AND METHODS. Two standardized neurobehavioral evaluations were completed on 207 infants at term equivalent, including 168 very preterm infants (<1250 g or <30 weeks' gestation) and 39 term control infants. The assessments used were the Neonatal Intensive Care Unit Network Neurobehavioral Scale and the revised Hammersmith Neonatal Neurologic Examination. The relationship of perinatal variables to preterm infant neurobehavioral scores for both evaluations was examined.

    RESULTS. Compared with term-born infants, preterm infant neurobehavior was significantly altered for the Hammersmith Neonatal Neurologic Examination total score and all of the subtotals. Similarly, preterm infants displayed altered neurobehavior for the majority of the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores. Complete perinatal data were available for 157 of 168 very preterm infants. The perinatal variables most strongly associated with altered preterm infant neurobehavior on multivariate regression analysis included the total number of days of assisted ventilation, intraventricular hemorrhage, and necrotizing enterocolitis. Positive perinatal influences on neurobehavioral performance at term on multivariate analysis included maternal antenatal steroids, female gender, and infants receiving breast milk at discharge home.

    CONCLUSIONS. Preterm infants at term equivalent showed alterations in motor behavior and higher cortically integrated functions. The pattern of abnormality in neurobehavior differed in relation to perinatal exposures. Neurobehavioral examination at term equivalent age is useful in evaluating the impact of neonatal intensive care.

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