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PubMed1997

Margin of safety for discharge after apnea in preterm infants.

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at </=32 weeks' gestational age or weighing </=1500 g at birth from two institutions to determine the intervals between the day on which the last apnea occurred and the previous two days on which apnea occurred. One hundred seventy-five infants were excluded because they never experienced apnea, or data about the last apnea was missing, or they were on xanthines during the period encompassing the last 3 apnea days, or they weighed <1500 g or were <34 weeks' postmenstrual age at the time of the last apnea. Of the 91 remaining infants, gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and discharge weight were not different between the two institutions. For each infant we determined the longest of the intervals between the 2 days on which apnea occurred previous to the day of the last apnea (MAXINT for maximum interval). The infants were then ordered by MAXINT and, starting at the longest MAXINT, the medical records of each infant were carefully examined for other conditions known to be associated with apnea (eg, recovering from anesthesia, sepsis, chronic lung disease, and so forth). The minimal safe observation period was then defined as the longest MAXINT in which there was at least 1 infant with no other explanation for the apnea other than prematurity. RESULTS: The median duration of the intervals between the 2 days on which apnea occurred previous to the day on which the last apnea occurred were 3. 0 and 2.0 days and the median duration of the MAXINT was 4.0 days. On careful examination of the charts, it was determined that each of 13 infants with a MAXINT preceding the day on which the last apnea occurred of greater than 8 days had some other condition that might result in apnea, including residual lung disease, sepsis, surgery, and so forth. In contrast, among the group of infants with a MAXINT of </=8 days, at least 1 infant at each MAXINT (eg, 1 to 8) had significant apnea with no other explanation other than prematurity. CONCLUSIONS: We conclude that otherwise healthy preterm infants continue to have apneas separated by as many as 8 days before the last apnea before discharge. Conversely, infants with longer apnea intervals often have identifiable risk factors other than apnea of prematurity.

Apnea↗

PubMed1998

Analgesia for neonatal circumcision: a randomized controlled trial of EMLA cream versus dorsal penile nerve block.

OBJECTIVE: To compare the efficacy of the dorsal penile nerve block (DPNB) with a less invasive form of local anesthesia, eutectic mixture of local anesthetic (EMLA) cream, for reduction of pain during neonatal circumcision. DESIGN: Prospective, blinded, randomized, controlled trial. SETTING: Tertiary referral, neonatal intensive care nursery in a university teaching hospital. PATIENTS: Fifty infants >/=341/2 weeks postmenstrual age and stable for discharge at time of circumcision; gestational age at birth 25 to 41 weeks; birth weight 600 to 4390 g; age at study 3 to 105 days. An additional cohort of term newborns (n = 20), who were not randomized, were circumcised without anesthesia. INTERVENTIONS: Administration of either EMLA cream (0.5 g topically 1 hour before circumcision) or 1% lidocaine (0.7-1.0 mL subcutaneously 3 minutes before circumcision). OUTCOME MEASURES: Primary: Neonatal Infant Pain Scale (NIPS) score; secondary: heart rate, respiratory rate. All outcome measures were assessed by an individual who was blinded to the group assignment and did not perform the circumcision. RESULTS: NIPS scores were significantly lower in the DPNB infants (2.3 +/- 1.8) compared with the EMLA infants (4.8 +/- 0.7). NIPS scores in patients circumcised without anesthesia indicated severe pain. There was a significantly greater increase in heart rate over the duration of the circumcision in the EMLA group than in the DPNB group (49 vs 9 beats per minute). Adverse effects included small hematomas at the site of injection in DPNB infants (10/23), mild erythema at 1 and/or 24 hours after circumcision in the EMLA infants (3/21), and penile edema noted 5 days after circumcision requiring removal of the circumcision bell in 1 DPNB infant. CONCLUSIONS: DPNB provides better pain reduction during neonatal circumcision than EMLA cream. EMLA cream may provide pain reduction compared with no anesthesia during neonatal circumcision.

Anesthesia, Local↗

PubMed1999

Longitudinal growth of hospitalized very low birth weight infants.

BACKGROUND: The interpretation of growth rates for very low birth weight infants is obscured by limited data, recent changes in perinatal care, and the uncertain effects of multiple therapies. OBJECTIVES: To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight, nutritional practices, fetal growth status (small- or appropriate-for-gestational-age), and major neonatal morbidities (chronic lung disease, nosocomial infection or late-onset infection, severe intraventricular hemorrhage, and necrotizing enterocolitis). DESIGN: Large, multicenter, prospective cohort study. METHODS: Growth was prospectively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31, 1994 and August 9, 1995. Infants were included if they survived >7 days (168 hours) and were free of major congenital anomalies. Anthropometric measures (body weight, length, head circumference, and midarm circumference) were performed from birth until discharge, transfer, death, age 120 days, or a body weight of 2000 g. To obtain representative data, nutritional practices were not altered by the study protocol. RESULTS: Postnatal growth curves suitable for clinical and research use were constructed for body weight, length, head circumference, and midarm circumference. Once birth weight was regained, weight gain (14.4-16.1 g/kg/d) approximated intrauterine rates. However, at hospital discharge, most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age. Gestational age, race, and gender had no effect on growth within 100-g birth weight strata. Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease, severe intraventricular hemorrhage, necrotizing enterocolitis, or late onset-sepsis gained weight faster than comparable infants with those morbidities. More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75% of the total daily fluid volume, an earlier age at the initiation of enteral feedings, and an earlier age at achievement of full enteral feedings. CONCLUSIONS: These growth curves may be used to better understand postnatal growth, to help identify infants developing illnesses affecting growth, and to aid in the design of future research. They should not be taken as optimal. Randomized clinical trials should be performed to evaluate whether different nutritional management practices will permit birth weight to be regained earlier and result in more rapid growth, more appropriate body composition, and improved short- and long-term outcomes.

Anthropometry↗

PubMed1999

Population-based study of chronic lung disease in very low birth weight infants in North Carolina in 1994 with comparisons with 1984. The North Carolina Neonatologists Association.

OBJECTIVE: To assess the pulmonary outcomes of very low birth weight (VLBW) infants in North Carolina in 1994 and to compare rates of survival and chronic lung disease (CLD) between 1994 and 1984 (see reference 2). METHODS: Data were collected prospectively by collaborators from all 13 neonatal intensive care units in North Carolina to determine survival and pulmonary outcomes of infants with birth weights of 500 to 1500 g. State vital statistics data were used to confirm completeness of the sample. CLD was defined as oxygen or ventilator therapy at 36 weeks' postmenstrual age (PMA). For comparisons with the 1984 cohort, survival and pulmonary outcomes of infants defined to be at risk for CLD (ventilated >48 hours and survived 30 days) were recorded at 30 days, 3 months, and 6 months of postnatal age. RESULTS: Outcome data were available for 1413 (92%) of the in-state VLBW live births. Of VLBW infants, 224 (15%) died before 48 hours of age. The overall rate of CLD in 1994 at 36 weeks' PMA was 25%. Rates by birth weight group were 57% for 500 to 750 g birth weight (BW), 41% for 751 to 1000 g BW, 19% for 1001 to 1250 g BW, and 8% for 1251 to 1500 g BW. Infants who received ventilator therapy for >48 hours accounted for 89% of the CLD cases. The CLD rate at 36 weeks' PMA in infants weighing 751 to 1500 g was 37% for those ventilated >48 hours versus 5% for those ventilated <48 hours (OR: 7.1; 95% CI: 4.4-11.3). Overall survival in 1994 was significantly higher for infants than in 1984 (78% vs 74%), most notably in infants 500 to 750 g BW (37% vs 24%), and 751 to 1000 g BW (82% vs 65%). When compared with 1984, the CLD rates in those infants defined to be at risk were significantly higher in 1994 at 30 days (68% vs 54%) and at 3 months (24% vs 15%) of postnatal age. For at-risk infants in 1994, there were fewer infants on the ventilator, but more infants on oxygen alone at all measured time points compared with 1984. CONCLUSION: Survival of VLBW infants has improved since 1984. Ventilator therapy for >48 hours remains a significant risk factor for CLD. The incidence of CLD has increased from 1984 to 1994 but has shifted from ventilator to oxygen therapy. bronchopulmonary dysplasia, epidemiology, infant, low birth weight, intensive care units, neonatal statistics, infant mortality, prospective studies.

Chronic Disease↗

PubMed2000

Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes.

OBJECTIVE: To determine the efficacy and safety of supplemental therapeutic oxygen for infants with prethreshold retinopathy of prematurity (ROP) to reduce the probability of progression to threshold ROP and the need for peripheral retinal ablation. METHODS: Premature infants with confirmed prethreshold ROP in at least 1 eye and median pulse oximetry <94% saturation were randomized to a conventional oxygen arm with pulse oximetry targeted at 89% to 94% saturation or a supplemental arm with pulse oximetry targeted at 96% to 99% saturation, for at least 2 weeks, and until both eyes were at study endpoints. Certified examiners masked to treatment assignment conducted weekly eye examinations until each study eye reached ophthalmic endpoint. An adverse ophthalmic endpoint for an infant was defined as reaching threshold criteria for laser or cryotherapy in at least 1 study eye. A favorable ophthalmic endpoint was regression of the ROP into zone III for at least 2 consecutive weekly examinations or full retinal vascularization. At 3 months after the due date of the infant, ophthalmic findings, pulmonary status, growth, and interim illnesses were again recorded. RESULTS: Six hundred forty-nine infants (325 conventional and 324 supplemental) were enrolled from 30 centers over 5 years. Five hundred ninety-seven (92.0%) infants attained known ophthalmic endpoints, and 600 (92%) completed the ophthalmic 3-month assessment. The rate of progression to threshold in at least 1 eye was 48% in the conventional arm and 41% in the supplemental arm. After adjustment for baseline ROP severity stratum, plus disease, race, and gestational age, the odds ratio (supplemental vs conventional) for progression was.72 (95% confidence interval:.52, 1.01). Final structural status of all study eyes at 3 months of corrected age showed similar rates of severe sequelae in both treatment arms: retinal detachments or folds (4.4% conventional vs 4.1% supplemental), and macular ectopia (3.9% conventional vs 3.9% supplemental). Within the prespecified ROP severity strata, ROP progression rates were lower with supplemental oxygen than with conventional oxygen, but the differences were not statistically significant. A post hoc subgroup analysis of plus disease (dilated and tortuous vessels in at least 2 quadrants of the posterior pole) suggested that infants without plus disease may be more responsive to supplemental therapy (46% progression in the conventional arm vs 32% in the supplemental arm) than infants with plus disease (52% progression in conventional vs 57% in supplemental). Pneumonia and/or exacerbations of chronic lung disease occurred in more infants in the supplemental arm (8.5% conventional vs 13.2% supplemental). Also, at 50 weeks of postmenstrual age, fewer conventional than supplemental infants remained hospitalized (6.8% vs 12.7%), on oxygen (37.0% vs 46.8%), and on diuretics (24.4% vs 35. 8%). Growth and developmental milestones did not differ between the 2 arms. CONCLUSIONS: Use of supplemental oxygen at pulse oximetry saturations of 96% to 99% did not cause additional progression of prethreshold ROP but also did not significantly reduce the number of infants requiring peripheral ablative surgery. A subgroup analysis suggested a benefit of supplemental oxygen among infants who have prethreshold ROP without plus disease, but this finding requires additional study. Supplemental oxygen increased the risk of adverse pulmonary events including pneumonia and/or exacerbations of chronic lung disease and the need for oxygen, diuretics, and hospitalization at 3 months of corrected age. Although the relative risk/benefit of supplemental oxygen for each infant must be individually considered, clinicians need no longer be concerned that supplemental oxygen, as used in this study, will exacerbate active prethreshold ROP.

Disease Progression↗

PubMed2000

Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network.

OBJECTIVE: To explore the hypothesis that variation in respiratory management among newborn intensive care units (NICUs) explains differences in chronic lung disease (CLD) rates. DESIGN: Case-cohort study. SETTING: NICUs at 1 medical center in New York (Babies' and Children's Hospital [Babies']) and 2 in Boston (Beth Israel Hospital and Brigham and Women's Hospital [Boston]). STUDY POPULATION: Four hundred fifty-two infants born at 500 to 1500 g birth weight between January 1991 and December 1993, who were enrolled in an epidemiologic study of neonatal intracranial white matter disorders. CASE DEFINITION: Supplemental oxygen required at 36 weeks' postmenstrual age. RESULTS: The prevalence rates of CLD differed substantially between the centers: 4% at Babies' and 22% at the 2 Boston hospitals, despite similar mortality rates. Initial respiratory management at Boston was more likely than at Babies' to include mechanical ventilation (75% vs 29%) and surfactant treatment (45% vs 10%). Case and control infants at Babies' were more likely than were those at Boston to have higher partial pressure of carbon dioxide and lower pH values on arterial blood gases. However, measures of oxygenation and ventilator settings among case and control infants were similar at the 2 medical centers in time-oriented logistic regression analyses. In multivariate logistic regression analyses, the initiation of mechanical ventilation was associated with increased risk of CLD: after adjusting for other potential confounding factors, the odds ratios for mechanical ventilation were 13.4 on day of birth, 9.6 on days 1 to 3, and 6.3 on days 4 to 7. Among ventilated infants, CLD risk was elevated for maximum peak inspiratory pressure >25 and maximum fraction of inspired oxygen = 1.0 on the day of birth, lowest peak inspiratory pressure >20 and maximum partial pressure of carbon dioxide >50 on days 1 to 3, and lowest white blood count <8 K on days 4 to 7. Even after adjusting for white blood count <8 K and the 4 respiratory care variables, infants in Boston continued to be at increased risk of CLD, compared with premature infants at Babies' Hospital. CONCLUSION: In multivariate analyses, a number of specific measures of respiratory care practice during the first postnatal week were associated with the risk of a very low birth weight infant developing CLD. However, after adjusting for baseline risk, most of the increased risk of CLD among very low birth weight infants hospitalized at 2 Boston NICUs, compared with those at Babies' Hospital, was explained simply by the initiation of mechanical ventilation.

Barotrauma↗

PubMed2001

Association of plasma cortisol and chronic lung disease in preterm infants.

BACKGROUND: It has been suggested that preterm infants may have developmental immaturity of the hypothalamic-pituitary-adrenal axis, and that decreased cortisol response to stress increases risk of chronic lung disease (CLD) secondary to inflammatory lung injury. METHODS: To investigate the relationship between endogenous corticosteroid and CLD, we measured plasma cortisol during the first 28 days of life in a subset of neonates in the North American Thyrotropin-Releasing Hormone (TRH) Collaborative Trial. Analyses were performed on 314 infants, 24 to 32 weeks' gestation, whose mothers received 1 or 2 courses of antenatal corticosteroids plus TRH or placebo. RESULTS: Mean cortisol was 3.1 microg/dL (range: 0.1-17.9) at birth, reached maximal levels at 24 hours (19.4 microg/dL, range: 0.8-124.6), and decreased to 5.9 microg/dL (range: 0.2-24.7) at 14 to 28 days of age; levels during the first week were not associated with gestational age. The Clinical Risk Index for Babies (CRIB), a neonatal assessment tool that is correlated with risk of mortality, was positively associated with cortisol level on days 1 and 3 through 7. TRH versus placebo treatment did not influence cortisol levels at any time point. To examine the relationship between cortisol and adverse outcome of death or CLD at 36 weeks' postmenstrual age (CLD36), logistic regression models adjusting for known contributing clinical factors (gestational age and CRIB score) were fit. There was a statistically borderline negative association between median cortisol level at 3 to 7 days and CLD36. After adjusting for gestational age and CRIB score, the predicted probability of CLD36 was only minimally influenced by the cortisol concentration. CONCLUSION: In preterm infants, basal plasma cortisol concentration during the first week is a weak predictor for CLD36. Possible benefits as well as risks of supplemental, low-dose cortisol treatment of high-risk preterm infants remain to be determined.

Bronchopulmonary Dysplasia↗

PubMed2001

Screening guidelines for retinopathy of prematurity: the need for revision in extremely low birth weight infants.

OBJECTIVE: To determine whether significant retinopathy of prematurity (ROP) can be detected before 31 to 33 weeks' postmenstrual age (PMA) in extremely low birth weight (ELBW) infants. METHODS: Medical records of all ELBW infants (<1000 g at birth) admitted to our regional perinatal center between April 1995 and January 1999 were reviewed retrospectively. Screening examinations for ROP were routinely performed at 4 to 6 weeks' chronological age (CA) from birth and followed at least every other week. Data were collected for infants who developed ROP. We determined the PMA at which the first screening eye examination demonstrated prethreshold disease and the subsequent examination that showed threshold disease (if it occurred). The percentages of infants who developed prethreshold ROP diagnosed at </=31 weeks' PMA and of those who progressed to threshold ROP before 34 weeks' PMA were determined. RESULTS: All 258 ELBW infants were screened for ROP. Seventy-eight infants (30%) were diagnosed with prethreshold ROP. Twenty-seven of these infants (35%) progressed to threshold ROP. Ten infants who progressed to threshold ROP were <34 weeks' PMA at the time of this diagnosis. Of these 10 infants, 3 were diagnosed at 31 weeks' PMA, 4 at 32 weeks', and 3 at 33 weeks'. CONCLUSION: More than 80% of ELBW infants who developed prethreshold disease in this cohort were </=33 weeks' PMA. The joint statement screening option of independently using 31 to 33 weeks' PMA for the first eye examination would have led to a diagnosis of threshold ROP on first examination in as many as 13% (10/78) of our patients. Early identification of prethreshold ROP is important for providing timely intervention in this rapidly progressive disease. Therefore, ELBW infants should receive initial ROP screening using the CA guideline of 4 to 6 weeks rather than the 31- to 33-week postconceptional age guideline.

Diagnostic Techniques, Ophthalmological↗

PubMed2001

Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.

OBJECTIVES: Preterm infants are frequently discharged from the hospital growth retarded and show reduced growth throughout childhood. In a large efficacy and safety trial, we tested the hypothesis that nutritional intervention in the first 9 months postterm would reverse postdischarge growth deficits and improve neurodevelopment without adverse safety outcomes. PARTICIPANTS AND INTERVENTION: Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229 were randomly assigned a protein, energy, mineral, and micronutrient-enriched postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9 months (Knobloch, Passamanick, and Sherrard's developmental screening inventory) and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm. RESULTS: At 9 months, compared with the TF group, those fed PDF were heavier (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head circumference. The effect of diet was greatest in males; at 9 months length deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI: 0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months' postterm. CONCLUSIONS: 1) Improving postdischarge nutrition in the first 9 months may "reset" subsequent growth-at least until 18 months for body length. We intend to follow-up the children at older ages. The observed efficacy of PDF was not associated with adverse safety outcomes. 2) We cannot reject the hypothesis that postdischarge nutrition benefits motor development and this requires additional study. 3) Our data raise the possibility that breastfed postdischarge preterm infants may require nutritional supplementation, currently under investigation.

Anthropometry↗

PubMed2001

Inter-neonatal intensive care unit variation in discharge timing: influence of apnea and feeding management.

BACKGROUND: Premature infants need to attain both medical stability and maturational milestones (specifically, independent thermoregulation, resolution of apnea of prematurity, and the ability to feed by mouth) before safe discharge to home. Current practice also requires premature infants to be observed in hospital before discharge for several days (margin of safety) after physiologic maturity is recognized. OBJECTIVE: To compare postmenstrual age (PMA) at discharge in a homogeneous population of premature infants cared for in different neonatal intensive care units (NICUs) and to assess the impact on hospital stay of the recognition and recording of physiologic maturity and the required margin of safety. METHODS: We studied premature infants delivered at 30 to 34 6/7 weeks gestational age (GA), free of significant medical or surgical complications. Medical records of 30 eligible infants consecutively discharged from the hospital before July 1997 from each of 15 NICUs in Massachusetts (9 level 2 and 6 level 3) were reviewed. RESULTS: A total of 435 infants were included in the study sample. Mean (+/- standard deviation) GA and birth weight of the study population were 33.2 +/- 1.2 weeks and 2024 +/- 389 g, respectively. Infants were discharged at a similar PMA regardless of GA at birth. Considerable variation in the PMA at discharge between hospital sites was observed (range, 35.2 +/- 0.5 weeks to 36.5 +/- 1.2 weeks). Despite the homogeneous study population, hospitals in which infants had the latest PMA at discharge also recorded mature cardiorespiratory and feeding behavior at an older age. Longer duration of pulse oximetry use was associated with later resolution of apnea. Differences in the duration of the margin of safety between sites did not contribute to variation in hospital stay. CONCLUSION: NICUs vary widely in length of hospital stay for healthy premature infants. We speculate that this variation results in part from differences in monitoring for and documentation of apnea of prematurity and feeding behavior.

Age Factors↗

PubMed2001

Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial.

OBJECTIVES: Infants of </=1250 g birth weight receive multiple erythrocyte transfusions during their hospitalization. We hypothesized that early erythropoietin (Epo) and iron therapy would 1) decrease the number of transfusions received (infants 401-1000 g birth weight; trial 1) and 2) decrease the percentage of infants who received any transfusions (1001-1250 g birth weight; trial 2). METHODS: A total of 172 infants in trial 1 and 118 infants in trial 2 were randomized to treatment (Epo, 400 U/kg 3 times weekly) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Complete blood and reticulocyte counts were measured weekly, and ferritin concentrations were measured monthly. Transfusions were administered according to protocol. Phlebotomy losses and transfusion data were recorded. RESULTS: Treated and placebo/control infants in trial 1 received a similar number of transfusions (4.3 +/- 3.6 vs 5.2 +/- 4.2, respectively). A similar percentage of treated and control infants in trial 2 received at least 1 transfusion (37% vs 46%). Reticulocyte counts were higher in treated infants during each week of the study in both trials. Hematocrits were higher among treated infants from week 2 on in both trials. Ferritin concentrations were higher in placebo/controls than in treated infants at weeks 4 and 8 in trial 1 and at week 4 in trial 2. No adverse effects of Epo or supplemental iron occurred. CONCLUSION: The combination of early Epo and iron as administered in this study stimulated erythropoiesis in infants who were </=1250 g at birth. However, the lack of impact on transfusion requirements fails to support routine use of early Epo.neonate, intravenous iron, donor exposure.

Anemia, Neonatal↗

PubMed2001

Diaphragm dimensions of the healthy preterm infant.

BACKGROUND: The diaphragm is the major inspiratory muscle in the neonate; however, human neonatal diaphragm development has not been extensively studied. We hypothesized that diaphragm thickness (t(di)) would be positively related to postmenstrual age (PMA), body weight, body length, head circumference, and nutritional intake. OBJECTIVES: To evaluate the evolution of diaphragm growth and motion in the healthy, preterm infant. METHODS: We used ultrasound to measure t(di) at the zone of apposition to the rib cage and diaphragm excursion (e(di)) during inspiration. Thirty-four stable, preterm infants (16 males and 18 females) between 26 and 37 weeks' PMA were studied during quiet sleep at weekly intervals until the time of discharge or transfer from the neonatal intensive care unit. All infants were clinically stable and not receiving ventilatory support. RESULTS: We found that 1) t(di) increased from 1.2 +/- 0.1 to 1.7 +/- 0.05 mm between 26 to 28 and 35 to 37 weeks' PMA; 2) t(di) was positively correlated with PMA (r = 0.40), body weight (r = 0.52), body length (r = 0.53), and head circumference (0.49), but not with postnatal nutritional intake (r = 0.09); and 3) e(di) decreased with increasing PMA. CONCLUSIONS: Our findings suggest that diaphragm development in premature infants scales with body dimensions. We speculate that the increase in t(di) with age is likely attributable to increased diaphragm muscle mass, and the reduced e(di) with age may be resulting from a reduction in chest wall compliance.

Analysis of Variance↗

PubMed2002

Correlates of lactation in mothers of very low birth weight infants.

OBJECTIVE: We sought to determine the correlates of intent to breastfeed and of successful lactation and nursing at the breast in mothers of very low birth weight (VLBW; <1.5 kg) infants. METHODS: We conducted a prospective observational study of 119 mothers of singleton VLBW infants (mean birth weight: 1056 g; mean gestational age: 28 weeks), 87 (73%) of whom intended to breastfeed. Mothers completed questionnaires at 3 weeks' postnatal age and at 35 and 40 weeks' (term) and 4 months' corrected ages (CAs). RESULTS: Of the 87 mothers who intended to breastfeed, 30 mothers (34%) continued lactation beyond 40 weeks' CA (postmenstrual plus postnatal age). Compared with mothers who discontinued lactation before this time, those who continued were older (31 vs 26 years), more were married (80% vs 39%), they had more than a high school education (70% vs 42%), and they were white (63% vs 35%). There were no significant differences in their infants' birth data or rates of neonatal morbidity. Significant correlates of lactation beyond 40 weeks' CA included beginning milk expression before 6 hours postdelivery, expressing milk > or =5 times per day, and kangaroo care. These correlates remained significant after controlling for maternal age, race, marital status, and education beyond high school. At 4 months' CA, 14 mothers (16%) were still lactating, 12 of whom were nursing at the breast. CONCLUSIONS: Increased maternal support specifically directed toward behavioral factors, including early and more frequent milk expression and kangaroo care, may improve the rates of successful lactation among mothers of VLBW infants who choose to breastfeed.

Adult↗

PubMed2003

Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase.

OBJECTIVE: To examine whether treatment of premature infants with intratracheal recombinant human CuZn superoxide dismutase (r-h CuZnSOD) reduces bronchopulmonary dysplasia and improves pulmonary outcome at 1 year corrected age. DESIGN: Three hundred two premature infants (600-1200 g birth weight) treated with exogenous surfactant at birth for respiratory distress syndrome were randomized to receive either intratracheal r-h CuZnSOD (5 mg/kg in 2 mL/kg saline) or placebo every 48 hours (as long as intubation was required) for up to 1 month of age. Short-term, as well as longer-term pulmonary outcome was assessed. RESULTS: There were no differences between groups in the incidence of death or the development of bronchopulmonary dysplasia (oxygen requirement with an Edwards chest radiograph score of >or=3) at 28 days of life or 36 weeks' postmenstrual age. r-h CuZnSOD was well-tolerated and not associated with significant increases in any adverse event. At a median of 1 year corrected age, health assessments and physical examinations were performed on 209 (80%) surviving infants, with complete data available on 189 infants. Thirty-seven percent of placebo-treated infants had repeated episodes of wheezing or other respiratory illness severe enough to require treatment with asthma medications such as bronchodilators and/or corticosteroids compared with 24% of r-h CuZnSOD-treated infants, a 36% reduction. In infants <27 weeks' gestation, 42% treated with placebo received asthma medications compared with 19% of r-h CuZnSOD-treated infants, a 55% decrease. Infants <27 weeks' gestation who received r-h CuZnSOD also had a 55% decrease in emergency department visits and a 44% decrease in subsequent hospitalizations. Growth measurements and the results of physical examinations were comparable between groups. CONCLUSIONS: These data indicate that treatment at birth with r-h CuZnSOD may reduce early pulmonary injury, resulting in improved clinical status when measured at 1 year corrected age. r-h CuZnSOD appears to be a safe and effective therapy that improves pulmonary outcome in high-risk premature infants.

Age Factors↗

PubMed2003

Chronic lung disease of prematurity and intrauterine growth retardation: a population-based study.

OBJECTIVE: To determine the risk of chronic lung disease (CLD) in small for gestational age (SGA) preterm infants in comparison to appropriately grown and large for gestational age (LGA) infants. METHODS: Observational study derived from a geographically defined population (Trent Health Region, United Kingdom). All preterm infants of or=90th centile). Both mortality and CLD rates (using both 28 days' and 36 weeks' postmenstrual age [PMA] definitions) were determined for these groups of infants. RESULTS: Four thousand fifty-one preterm infants <or=32 weeks' gestation were identified. SGA infants showed higher mortality before 28 days' postnatal age and 36 weeks' PMA as compared with reference group infants (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.49-2.72; and OR: 2.00, 95% CI: 1.49-2.69), respectively. SGA infants showed a significantly greater risk of developing CLD, both at 28 days' and 36 weeks' PMA as compared with the reference group infants (OR: 1.34, 95% CI: 1.03-1.74; and OR: 1.87, 95% CI: 1.39-2.51), respectively. LGA infants showed a trend toward a reduced incidence of CLD in comparison to the reference group, which was statistically significant for the 36 weeks' definition (OR: 0.76-28 weeks, 95% CI: 0.57-1.01; and OR: 0.55-36 weeks, 95% CI: 0.37-0.81). CONCLUSIONS: Fetal growth seems to influence mortality in general and morbidity, attributable to CLD, in particular in preterm infants. SGA preterm infants are at higher risk of death before 28 days' and 36 weeks' PMA and CLD by both definitions. LGA infants show reduced risk of CLD.

Birth Weight↗

PubMed2004

Perception of child vulnerability among mothers of former premature infants.

OBJECTIVES: Parents of premature infants often perceive their infants as medically vulnerable. High parental perception of child vulnerability (PPCV) is associated with disproportionately high health care utilization. The objectives of this study were to determine whether higher PPCV is correlated with worse developmental outcome in premature infants at 1-year adjusted age and to identify factors, present at neonatal discharge, that predict high PPCV. METHODS: This prospective cohort study assessed mothers of 116 premature infants who were </=32 weeks' gestation and required supplemental oxygen at 36 weeks postmenstrual age. At neonatal discharge, mothers completed the Spielberger State Anxiety Inventory, Beck Depression Inventory, Impact on Family Scale, Life Orientation Test, General Health Survey, and Medical Outcomes Study social support survey. At 1-year adjusted age, child development was assessed using the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales, and mothers completed the Vulnerable Child Scale, a 16-item self-report measure of PPCV. Chart review was performed to determine the presence or absence of specific indicators of medical vulnerability at 1-year adjusted age. RESULTS: Mean infant gestational age and birth weight were 26.5 +/- 2.5 weeks and 894 +/- 287 g. A total of 69% of mothers were white, and 78% were high school graduates. Higher PPCV (lower Vulnerable Child Scale score) was correlated with lower scores on the Vineland Adaptive Behavior Composite and Bayley Psychomotor Developmental Index but not on the Bayley Mental Developmental Index. After controlling for the presence of 1 or more indicators of medical vulnerability, higher PPCV was still correlated with lower adaptive development. This correlation was stronger in the group of children with no indicators of medical vulnerability. In univariate analyses, higher PPCV was predicted by nonfirstborn status; longer neonatal hospitalization; higher maternal anxiety and depression; greater impact of the illness on the family; and lower maternal optimism, life satisfaction, and social support. PPCV was not associated with maternal age, education, marital status, income, or ethnicity or with child gender, gestational age, birth weight, or length of mechanical ventilation. A linear regression model containing all variables significant at the univariate level explained 29% of the variance in PPCV. Maternal anxiety was the only variable that was statistically significant in the full model. CONCLUSIONS: Higher PPCV is associated with worse developmental outcome in premature infants at 1-year adjusted age. Maternal anxiety at neonatal discharge predicts later high PPCV. Interventions to prevent or decrease PPCV in premature infants should be targeted at parents who are more anxious at hospital discharge.

Analysis of Variance↗

PubMed2004

Bias in reported neurodevelopmental outcomes among extremely low birth weight survivors.

OBJECTIVES: The purpose of this study was to investigate possible bias in the evaluation of neurodevelopment and somatic growth at 18 to 22 months' postmenstrual age among extremely low birth weight (ELBW) survivors (401-1000 g at birth). METHODS: Data from a cohort of 1483 ELBW infant survivors who were born January 1993 through December 1994 and cared for at centers in the Neonatal Research Network of the National Institute of Child Health and Human Development were examined retrospectively. Children who were compliant with an 18- to 22-month follow-up visit, who visited but were not measured, or who made no visit were compared regarding 4 outcomes: 1) Bayley Scales of Infant Development, 2nd edition, Mental Developmental Index (MDI) <70 and 2) Psychomotor Developmental Index (PDI) <70, 3) presence or absence of cerebral palsy, and 4) weight <10th percentile for age. Logistic regression models were used to predict likelihood of these outcomes for children with no follow-up evaluation, and predicted probability distributions were compared across the groups. RESULTS: Compared with children who were lost to follow-up, those who were compliant with follow-up were more likely to have been 1 of a multiple birth, to have received postnatal glucocorticoids, and to have had chronic lung disease. These factors were significantly associated with MDI and PDI <70 in the compliant group. Chronic lung disease was associated with increased risk of cerebral palsy (CP). MDI and PDI scores <70 were found in 37% and 29% of children who were evaluated at follow-up, respectively. Prediction models revealed that 34% and 26% of infants in the no-visit group would have had MDI and PDI scores <70. Compliant children tended to have greater incidence of MDI <70 compared with those predicted in the no-visit group but not PDI <70. CP was identified in 17% of the compliant group and predicted for 18% of the no-visit group. Predicted probabilities of having CP were marginally higher among the no-visit infants compared with those who were compliant with follow-up. There were no statistically significant somatic growth differences among the compliant, visit but not measured, and no-visit groups. CONCLUSION: ELBW infant survivors who weighed 401 to 1000 g at birth and who are compliant with follow-up evaluations may have worse Bayley Scales of Infant Development, 2nd edition, MDI scores than infants with no visit. Thus, follow-up studies based on infants who are compliant with follow-up care may lead to an overestimation of adverse outcomes in ELBW survivors.

Bias↗

PubMed2004

Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants.

OBJECTIVE: To compare the value of serial cranial ultrasound (US) with a single magnetic resonance imaging (MRI) before discharge in very low birth weight preterm infants to predict cerebral palsy (CP). METHODS: Infants who weighed <1250 g at birth and were <30 weeks' gestational age underwent conventional brain MRI at near term (36-40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner. Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient recalled echo images were obtained. Cranial US was also obtained at least twice during the first 2 weeks of life. MRI and US images were interpreted by 2 independent radiologists, who were masked to clinical outcome, and scored as follows: category 1, no abnormality; category 2, subependymal hemorrhage or mineralization; category 3, moderate to severe ventriculomegaly; category 4, focal parenchymal abnormality with or without ventriculomegaly. For the purpose of this study, 1 and 2 were categorized as "normal," and 3 and 4 were categorized as "abnormal." The infants were assessed at a mean age of 20 and 31 months using the Amiel-Tison standardized neurodevelopmental examination. RESULTS: The sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months. CONCLUSIONS: As a predictor of outcome for CP, MRI at near-term in very low birth weight preterm neonates is superior to US. However, both US and MRI demonstrate high specificity.

Brain↗