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The pattern of eosinophilia in premature infants. A prospective study in premature infants using the absolute eosinophil count.

The incidence and severity of eosinophilia was prospectively studied in 45 premature infants, who were divided into three groups according to their gestational age. The incidence and severity of eosinophilia was higher in small preterm infants. A significantly higher number of infants with eosinophilia received total parenteral nutrition, endotracheal intubation, or blood transfusions. The duration of total parenteral nutrition or endotracheal intubation and the number of blood transfusions were also significantly higher in infants with eosinophilia. Eosinophilia in premature infants is not associated with neutropenia.

Birth Weight↗

Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

BACKGROUND: There exists no reliable information that allows the ophthalmologist to predict with any degree of certainty a particular infant's chances of requiring surgical treatment for retinopathy of prematurity (ROP) or of reaching an unfavorable outcome on the basis of the retinal findings at the time of the nursery examination. METHODS: In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), 4099 infants weighing less than 1251 g at birth underwent eye examinations that began at 4 to 6 weeks after birth and subsequently continued at 2-week intervals. Independent variables in the population were studied using multiple logistic regressions. RESULTS: An increased risk of reaching threshold ROP was found associated with lower birth weights, younger gestational age, white race, multiple birth, and being born outside a study center nursery. For infants who developed ROP (66%), corresponding probabilities are presented for developing severe ("threshold") ROP or of having an unfavorable macular outcome. The risk of an unfavorable macular outcome was increased with zone 1 ROP, "plus" disease, the severity of the stage, and the amount of circumferential involvement. A higher risk also was associated with a rapid rate of progression of ROP to prethreshold disease but not with the postconceptional age at which ROP was first noted. CONCLUSION: The findings indicate that the ocular characteristics of ROP, along with some easily identifiable and available basic systemic and demographic information about an infant, can assist the ophthalmologist in understanding variations in an individual baby's chance for a good or poor macular outcome.

Child, Preschool↗

[Effect and correlation of various risk factors in the development of retinopathy of prematurity. A retrospective study of 338 premature infants].

The statistical significance of ophthalmological and pediatric findings in the development of retinopathy of prematurity (ROP) was evaluated in a retrospective study of 338 premature infants. Short gestation time, frequent hypoxia, and low birthweight were strongly correlated with advanced stages of ROP. The influence of Vitamin E treatment, duration of oxygen therapy, and need for transfusions was less significant. Neither multiple births nor the infant's sex had any influence on the development of ROP. Cryotherapy appears to reduce ROP, but the number of cases in the present study was too small to permit statistical analysis.

Birth Weight↗

Premature infants require additional folate and vitamin B-12 to reduce the severity of the anemia of prematurity.

One hundred eighty-four premature infants, < 1800 g at birth and < 36 wk gestation, were entered into a study investigating the role of additional folate and vitamin B-12 supplementation of the anemia of prematurity. All patients initially received vitamin E and iron in accordance with accepted standards. Patients were randomly assigned to four groups to receive orally 0.1 mg folate/d for 4 mo, 100 micrograms vitamin B-12 intramuscularly monthly for 4 mo, both supplements, or neither. All other activities including parenteral nutrition were carried out according to established practices, irrespective of study group. By 10-12 wk, infants treated with vitamin B-12 alone or combined with folate had higher hemoglobin values than the untreated (P < 0.0005) or solely folate-treated (P < 0.01) groups. These findings held true irrespective of wide variations in treatment and feeding practices. The only uncontrolled hematologic nutritional factor, selenium, showed a similar pattern of decline for 10-12 wk in all study patients, whether or not they received additional vitamin supplements.

Anemia↗

Methylxanthine therapy for apnea of prematurity: evaluation of treatment benefits and risks at age 5 years in the international Caffeine for Apnea of Prematurity (CAP) trial.

Methylxanthine therapy reduces the frequency of apnea and the need for mechanical ventilation. Recent research has raised concerns about the safety of methylxanthines in very preterm infants. Possible adverse effects include poor growth, worsening of hypoxic-ischemic brain damage and abnormal childhood behavior. Over 2,000 infants with birth weights 500-1,250 g have been randomized in the international placebo-controlled Caffeine for Apnea of Prematurity (CAP) trial to examine the long-term efficacy and safety of methylxanthine therapy for the management of apnea of prematurity. Additional therapies such as continuous positive airway pressure were used as necessary to control apneic attacks. At 18 months we measure the combined rate of death or survival with one or more of the following impairments: cerebral palsy, cognitive deficit, blindness and deafness. This outcome was chosen because of the need to evaluate the impact of common neonatal therapies beyond discharge from the intensive care unit. However, several potential long-term consequences of methylxanthine therapy may not become apparent until the study cohort reaches pre-school age. We will therefore extend the follow-up to age 5 years. The main outcome at 5 years will be a composite of death or survival with severe disability in at least one of six domains: cognition, neuromotor function, vision, hearing, behavior, and general health. Once this project is completed, caffeine will be one of the most rigorously evaluated neonatal therapies.

Aging↗

In vitro effects of inosine-pyruvate-phosphate on P50 values and DPG contents of fresh and stored blood from healthy neonates, symptom-free premature infants and premature infants with respiratory distress syndrome.

A study was made of the effect of a 3-hour incubation with inosine-pyruvate-phosphate (IPP) on the P50 values and 2,3-DPG contents of fresh blood and blood which had stood for 96 h, from healthy adults, term neonates, 1-2-week-old symptom-free premature infants and RDS premature infants. It was found that the P50 value and the 2,3-DPG content could be increased considerably by IPP treatment in both the fresh and the stood blood in the various groups of neonates. The question remains open as to whether the effect of IPP, in significantly improving the O2 transport in neonates, is a consequence of the 2,3-DPG alone or of some other metabolite. In RDS the stimulating effect of the IPP mixture is appreciably lower.

Adult↗

Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. METHODS: Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). RESULTS: Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. CONCLUSION: Severity of neonatal ROP seems to be a marker for functional disability at age 5. 5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Child, Preschool↗

[Humoral immune response to the retinal S-antigen in premature infants and its role in the development and course of retinopathy of prematurity].

The humoral immune response to the retinal S-antigen was studied in premature babies with active and cicatricle stages of retinopathy of the premature (RP) and in the controls (102 serum test). The presence of antibodies to the S-antigen of classes IgG and IgM was established by the enzyme multiplied analysis and by an authors' developed test-system. A definite specific humoral response to the S-antigen correlated with the nature of the course and prognosis of the disease was found in 71% of cases. The first peak of IgM-antibodies was found in babies of the risk-group (preretinopathy), it correlated with a poor prognosis (progression of RP). The second peak was highly pronounced in babies with the terminal cicatricle stages of RP. The wave-like dynamics of IgG-antibodies suggests that specific circulating immune complexes shape up. The role of immune responses, induced by the retinal S-antigen, in the RP pathogenesis is discussed.

Antibody Formation↗

[Effect of gentle nursing care of premature infants on bonding and emotional development of the child. Follow-up of premature infants in Dr. Marina Marcovich's study].

The study was set out to investigate whether the Marcovich model of a "soft treatment" of premature infants encourages the parent-infant-relationship to such an extent that, at school age, the Marcovich-children would be found to differ significantly from children treated with standard care with regard to the quality of their attachment and the prevalence of emotional and behavioural disorders. The Marcovich-children of the present sample had been discharged from hospital much earlier than the standard group, they were less frequently treated with artificial respiration, infant-parent body contact was encouraged significantly earlier, and, although they were less frequently breast-fed, those who were breast-fed were allowed to do so at a much earlier stage. The Marcovich-children were found to display higher social competence, more emotional openness, more emotional coherence, less dismissal of attachment and less preoccupied anger. The two samples did not differ with regard to their total attachment quality as well as their emotional and behavioural problems. The fact that no significant differences could be established with regard to the quality of the attachment suggests that the complex life-saving attachment system is not irreversibly affected by the early separation and distress and that the months and years after the hospital stay have the power to make up with any experienced trauma. It seems, however, that special aspects of the attachment system, such as the communication and interaction, are positively encouraged and enhanced by the soft treatment of the premature infant, which leads to greater emotional openness and social competence, as well as less preoccupied anger against the attachment figures.

Adolescent↗

[Observation and follow-up of premature rupture of the membranes. A pilot study of women at term with immature cervix and premature rupture of the membranes, without contractions].

In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer.

Adult↗

[Risk of infection in premature infants with premature rupture of fetal membranes in correlation to respiratory distress syndrome].

The spectrum of infective agents in 58 preterm deliveries with premature rupture of the membranes (PROM) is examinated by assessment of bacteriological swabs. In the earliest weeks of gestation all children had severe RDS. Nearly 40% of the detected pathogens belonged to the non pathogenic vaginal flora. E. coli, Streptococcus species, Klebsiella and Candida were predominant in the group of facultative pathogenic infective agents. There is an enlarged colonization in maternal swabs after greater than 24 h. In nearly 80% of the children with severe RDS pathogens could be detected. Ascending infection is followed more often by severe RDS. In case of premature labor refractory to tocolytic therapy or slight vaginal bleeding, cervical swabs should be taken. Pathological findings must be treated by local antiseptic agents or antibiotic therapy. If there are any signs of intrauterine infection the pregnancy must be terminated to avert damage from the newborn.

Bacteria↗

Thyroid function in premature infants. The hypothyroxinemia of prematurity.

Advances of perinatal and neonatal medicine have been associated with a progressive reduction in mortality of premature infants and a progressive increase in number of the surviving very low birth weight (VLBW) cohort less than 28 to 32 weeks gestation age. Hypothalamic-pituitary-thyroid (HPT) function is immature in most premature infants, and this is particularly true of the VLBW group. Accumulated information has allowed development of a unique nosology of HPT system disorders in these infants to facilitate thyroid function testing, test interpretation, and patient management.

Congenital Hypothyroidism↗

Central nervous system damage and retinopathy of prematurity--an ophthalmic follow-up of prematures born in 1982-84.

Retinopathy of prematurity (ROP) was observed in 28 of 185 pre-term infants born in 1982-84 and under regular ophthalmic surveillance after delivery; their gestational age (GA) range was 25-35 weeks; four became blind. All 28 attended ophthalmic reassessment at age 7-10 years and were compared with 60 pre-term subjects of the same cohort who had not developed ROP. Considering psychomotor development, 45 (51%) of the total 88 had evidence of central nervous system (CNS) damage; minor in 24 and major in 21 (cerebral palsy in particular). With correction for drop-outs, the regional frequency of severe CNS damage was 24% for birth weight below 1500 g and 29.6% for GA less than 32 weeks. Except for the selection due to initial inclusion for ROP surveillance, we have no explanation for the high frequency at the present follow-up. Statistically, the ocular damage of ROP appeared unassociated with CNS impairment. An analysis of perinatal factors based on matched pairs did not indicate any definite association with subsequent development of ROP and/ or CNS damage.

Central Nervous System Diseases↗

Premature expression of cyclin B sensitizes human HT1080 cells to caffeine-induced premature mitosis.

Eukaryotic cells do not normally initiate mitosis when DNA replication is blocked. This cell cycle checkpoint can be bypassed in some cells, however, by treatment with caffeine and certain other chemicals. Although S-phase arrested hamster cells undergo mitosis-specific events such as premature chromosome condensation (PCC) and nuclear envelope disassembly when exposed to caffeine, human cells show little response under the same conditions. To further investigate the molecular basis of this cell type specificity, a panel of hamster/human whole cell hybrids was created. The frequency of caffeine-induced PCC and the level of cyclin-B-associated H1 kinase activity in the various hybrids were directly correlated with the extent of cyclin B synthesis during S-phase arrest. To determine whether expression of cyclin B alone could sensitize human cells to caffeine, cyclin B1 was transiently overexpressed in S-phase arrested HT1080 cells. The transfected cell population displayed a 5-fold increase in the frequency of caffeine-induced PCC when compared with normal HT1080 cells, roughly equivalent to the frequency of cells expressing exogenous epitope-tagged cyclin B1. In addition, immunofluorescent microscopy showed that individual cells overexpressing cyclin B1 during S phase arrest underwent PCC when exposed to caffeine. These results provide direct evidence that premature expression of cyclin B1 can make cells more vulnerable to chemically-induced uncoupling of mitosis from the completion of DNA replication.

Animals↗

Stimulation of premature retinoic acid synthesis in Xenopus embryos following premature expression of aldehyde dehydrogenase ALDH1.

In order for nuclear retinoic acid receptors to mediate retinoid signaling, the ligand retinoic acid must first be produced from its vitamin A precursor retinal. Biochemical studies have shown that retinal can be metabolized in vitro to retinoic acid by members of the aldehyde dehydrogenase enzyme family, including ALDH1. Here we describe the first direct evidence that ALDH1 plays a physiological role in retinoic acid synthesis by analysis of retinoid signaling in Xenopus embryos, which have plentiful stores of maternally derived retinal. The Xenopus ALDH1 gene was cloned and shown to be highly conserved with chick and mammalian homologs. Xenopus ALDH1 was not expressed at blastula and gastrula stages, but was expressed at the neurula stage. We used a retinoic acid bioassay to demonstrate that retinoic acid is normally undetectable in embryos from fertilization to the initial gastrula stage, but that a tremendous increase in retinoic acid occurs during neurulation when ALDH1 is first expressed. Overexpression of ALDH1 by injection of Xenopus embryos with mRNAs encoding the mouse, chick or Xenopus ALDH1 homologs induced high levels of retinoic acid detection during the blastula stage. Thus, premature expression of ALDH1 stimulates premature synthesis of retinoic acid. These findings reveal an important conserved role for ALDH1 in retinoic acid synthesis in vivo, and demonstrate that conversion of retinoids from the aldehyde form to the carboxylic acid form is a crucial regulatory step in retinoid signaling.

Aldehyde Dehydrogenase↗

Temporal and spatial dispersion of repolarization during premature impulse propagation in human intact ventricular muscle: comparison between single vs double premature stimulation.

AIMS: This study was performed to determine whether or not the kinetics of action potential duration restitution during double premature stimuli (S3) differ from that during single premature stimuli (S2) in the human intact right ventricle. METHODS AND RESULTS: A monophasic action potential (MAP) was simultaneously recorded from the right ventricular apex (RVA) and outflow tract (RVOT) during programmed ventricular pacing in 11 patients with symptomatic bradyarrhythmias (five males, six females, mean age 58 years). In the five most recent patients, the RV pressure and its dp/dt were also obtained during the protocol. A substantial difference in the restitution of the MAP duration (MAPD) between S2 and S3 was observed at short diastolic intervals (< l00 ms), that is, the restitution curve of S2 showed an early biphasic pattern (upward hump), while such a phenomenon was not seen during the restitution of S3. All the quantitative parameters of MAPD restitution representing its kinetics were significantly greater in S3 than S2. Maximum attainable dispersion of repolarization between the two MAPs was significantly greater during S3 than S2 (76 +/- 17 vs 59 +/- 17 ms, P<0.05) and was mainly caused by the difference in the MAPD difference, thus by the difference in the restitution kinetics of S2 and S3. The dp/dt of the RV pressure was significantly greater during S3 than S2 for all diastolic intervals tested. CONCLUSION: It was concluded that similar to previously reported canine experimental studies, the APD restitution of S3 is substantially different from that of S2 in the human intact ventricle (endocardium).

Action Potentials↗

Normal and almost normal precocious variations in pubertal development premature pubarche and premature thelarche revisited.

Premature pubarche, premature thelarche and complete precocious puberty are usually simply normal phenomena occurring at an early age. This is not necessarily the case, however, and they may sometimes be harbingers of reproductive endocrine disturbances in adulthood. Consequently, girls with these complaints cannot be entirely reassured that they are of no consequence, and they should be followed to ascertain whether pubertal reproductive function is eventually normal.

Androgens↗

Mechanisms for absence of inverse relationship between coupling intervals of premature impulses initiating reentrant ventricular tachycardia and intervals between premature and first tachycardia impulses.

BACKGROUND: During initiation of tachycardias by programmed stimulation (PES), an inverse relationship between the coupling interval of the premature impulse (V1V2) and the interval between the premature impulse and the first impulse of tachycardia (V2T1) has been proposed to be a specific indicator of reentry. However, an inverse relationship has not always been observed during initiation of clinical reentrant ventricular tachycardias (VTs). METHODS AND RESULTS: Reentrant VT was initiated by PES in twelve 4-day-old infarcted dog hearts. The relationship between V1V2 and V2T1 was always direct. Mapping of the epicardial border zone (EBZ) indicated that initiation of VT was secondary to functional orthodromic block of V2, propagation of V2 around the line of block, and antidromic propagation through the original location of the block. In 7 dogs, the line of orthodromic block and the pathway of orthodromic propagation were similar for different V1V2 coupling intervals. Orthodromic conduction time around the line to its distal side was longer at shorter V1V2 intervals, but a shorter antidromic delay in the area of unidirectional block for shorter V1V2 intervals, possibly reflecting small changes in the conduction pathway involving deeper layers of the EBZ, resulted in shorter V2T1 intervals. In the other 5 dogs, the orthodromic conduction pathway of V2 around the line of block changed markedly, with a shorter pathway for shorter V1V2 intervals resulting in shorter V2T1 intervals. CONCLUSIONS: An inverse relationship between V1V2 and V2T1 is not a specific indicator of functional reentry.

Animals↗