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Serum concentrations of 25-hydroxyvitamin D in rickets of extremely premature infants.

Nine premature infants developed radiographic and biochemical rickets at a mean +/- SD of 12.6 +/- 2.8 weeks of age. Serum 25-hydroxyvitamin D concentrations were all low, with a mean of less than 3.6 +/- 2.1 ng/ml. The mean average daily intake of vitamin D since birth had been 300 +/- 181 IU, and the mean average daily intake during the week of diagnosis was 587 +/- 313 IU. All of the infants were extremely premature (mean weight 948 +/- 153 gm, mean gestation 27.7 +/- 1.1 weeks), and were being fed either a low-calcium "human milk-like" formula or a soy formula. It is postulated that low-calcium intake may have increased 25-OHD utilization in the face of a decreased ability of the extremely premature infant to produce 25-OHD. Because of multiple factors leading to both decreased production and possible increased utilization of 25-OHD, such infants have an increased requirement for vitamin D to maintain normal serum 25-OHD concentrations, and daily intakes of at least 400 IU vitamin D orally must be assured. Serum 25-OHD measurements and radiographs may be important in following infants at risk.

Humans

Coagulation studies in extremely premature infants.

Evidence of developmental evolution of coagulation can be seen when the studies of 10 thriving extremely premature (EPT) infants are compared to normal full-term (FT) infants. The prothrombin time, partial thromboplastin time, and thrombin time all became shorter with increasing gestational age. Fibrinogen levels and platelet counts appear to be comparable to term infant and adult levels. Fibrin degradation products (FDP) of 10 micrograms/ml or less were found in the thriving EPT infants. When compared to healthy full-term infants, there is a definite gestational dependency of anti-thrombin III levels. Factors II and VII appear to be related to intrauterine maturation after the age of viability (24 wk), but factor VII-X complex does not. The contact factors XI, XII, high molecular weight kininogen (Fitzgerald factor), and prekallikrein (Fletcher factor) are all markedly decreased in thriving EPT infants. The mean factor V level is lower than that found in FT infants. This study confirms a gestational age dependency of factor VIII activity. The ratio of factor VIII antigen to factor VIII clotting activity is increased (2.8 vs 1.01 in FT and adults). Thriving small for gestational age (SGA) infants had coagulation studies which were not statistically different from those of thriving EPT infants. The coagulation changes which occurred in severely ill EPT were mainly in the factors which decrease during intravascular coagulation (factors I, V, and VIII). The present study suggests that because of the high antigen to activity ratio seen in thriving EPT infants, a dysfunctional or fetal factor VIII may have been produced. However, the further elevation of this ratio in the severely ill EPT infants is in keeping with a pathologic proteolysis or increased endothelial release of factor VIII antigen.

Blood Coagulation Factors

Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial.

IMPORTANCE: Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. OBJECTIVE: To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. DESIGN, SETTING, AND PARTICIPANTS: This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. EXPOSURES: All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. MAIN OUTCOMES AND MEASURES: Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage &#x2265;3 and/or treated) and postnatal age. RESULTS: A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; &#x3b2;&#x2009;=&#x2009;0.68; 95% CI,&#x2009;0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; &#x3b2;&#x2009;=&#x2009;0.21; 95% CI,&#x2009;0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. CONCLUSIONS AND RELEVANCE: In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03201588.

Humans

Apnea in the premature infant: an overview of causes and treatment.

In summary, apnea of prematurity is both a primary and a secondary disorder--a reflection of CNS immaturity as well as a response to an underlying problem. Premature infants are extremely vulnerable to developing apnea. Close monitoring by the nursing staff and early detection and treatment of apnea and its associated disorders are essential to insure optimal growth and development of these tiny infants.

Anemia, Neonatal

Long-term motor outcomes after parent-administered early physiotherapy in children born very preterm.

OBJECTIVE: This observational follow-up study investigated whether early parent-administered physiotherapy during the neonatal period was associated with motor outcomes in childhood, and compared these outcomes between two preterm groups and a term-born control group. STUDY DESIGN: This is a follow-up of a pragmatic randomised controlled trial that initially included 153 infants born very preterm (&#x2264;32&#xa0;weeks' gestation), randomised to either early parent-administered physiotherapy or standard care, between 34 and 37&#xa0;weeks' gestation. At 7-10&#xa0;years, motor outcomes were assessed in 92 children (intervention, n&#xa0;=&#xa0;43; standard care, n&#xa0;=&#xa0;49) and in 83 term-born controls. The primary outcome was the Movement Assessment Battery for Children-Second Edition (MABC-2). Group differences were analysed using linear mixed models adjusted for age, sex, and parental education. Odds ratios (ORs) were calculated for scores &#x2264;5th and&#xa0;&#x2264;&#xa0;15th percentiles to estimate the likelihood of having or being at risk for movement difficulties. RESULTS: Mean MABC-2 total score was 9.0 (SD3.0) in the intervention group, 9.6 (SD3.0) in the standard care group, and 10.8 (SD2.9) in the control group. Adjusted mean difference between the intervention and the standard care groups did not differ but both the intervention and standard care groups had lower scores than the control group (-1.2; 95% CI: -2.3 to -0.2 and -0.6; 95% CI: -1.6 to 0.3, respectively). Adjusted ORs for scoring &#x2264;5th or &#x2264;15th percentile did not differ in either preterm group compared with the control group. CONCLUSION: At 7-10&#xa0;years, motor outcomes did not differ between children born very preterm who received three-week parent-administered physiotherapy and those who received standard care during the neonatal period. However, both preterm groups had lower motor scores than term-born peers.

Humans

[Intrauterine growth retardation of newborns with congenital anomalies].

The authors examined 11,799 newborns whose intrauterine life lasted from 28 to 42 weeks. In the group of dysmature infants (443) malformations were present in 11% and in the group of prematures (841) in 4.3%. Malformations were divided according to localization. The most significant difference was observed in the occurrence of malformations of the extremities (dysmature infants 27.17% and prematures 15.79%). It is concluded that malformations appear to be considerably more frequent in dismature infants than in prematures and that by their presence they affect the child's intrauterine growth.

Congenital Abnormalities

Measles as a cause of fetal defects. A retrospective study of tem measles epidemics in Greenland.

In a retrospective study of ten epidemics of measles in virgin-soil populations in Greenland, 368 women were found to be pregnant at the time of their infection with measles. Information on the course of the pregnancies was obtained in 327 of these women and a clinical examination was made of 252 of their children. The risk of fetal death among women infected in the first trimester was found to be high. About half of 20 women infected during their first two months of pregnancy and a fifth of 31 women infected in the third month had abortions. 9% of 64 women infected in the first trimester and going to term had stillbirths. 28 women infected in the first two months of pregnancy had live children, but four of these had congenital malformations, three of extreme rarity and severity, leading to death. The rate of perinatal mortality and prematurity was equal among infants exposed to measles in the first, second and third trimester of fetal life.

Congenital Abnormalities

[Campomelic syndrome (author's transl)].

A female premature infant with dwarfism, peculiar facial features, cleft palate and bone anomalies including bowing of the lower extremities with pretibial skin dimpling, the so called "campomelic syndrome" is presented. Other symptoms were hypotonia and respiratory distress. The radiological and autopsy findings in this child are described. The lack of known teratogenic factors during the pregnancy and the available data about the familial occurance of this malformation syndrome suggest the possibility of an autosomal recessive mode of inheritance in this patient. This is the first case of campomelic syndrome reported from Iran.

Abnormalities, Multiple

Acute pneumonia in the newborn: changing picture.

Pneumonia is one of the most serious infections in the neonate and is responsible for a large percentage of neonatal mortality. Pneumonia in a premature or term infant who is debilitated by an underlying problem such as hyaline membrane disease carries an extremely high morbidity and mortality. Since most of the bacterial pneumonias are treatable, early recognition and diagnosis and vigorous treatment are essential. X-ray findings, though helpful, serve only as a guideline. Prognosis is adversely affected if pneumonia results in generalized sepsis, leading to meningitis, disseminated intravascular coagulation, and osteomyelitis. Prompt antibiotic treatment should be begun before the etiologic agent or drug susceptibility is known.

Acute Disease

Femoral bifurcation with tibial aplasia. A case report and review of the literatures.

An extremely rare femoral bifurcation in combination with ipsilateral tibial aplasia, lumbosacral myelomeningocele, anomalies of hand and feet occurred in a premature infant. Review of the pertinent literature suggests that femoral bifurcation usually occurs in association with ipsilateral tibial aplasia. The pathogenesis of this rare congenital anomaly may be associated with an ectopic tibial anlage in the femur and insertions of disorganized muscles.

Abnormalities, Multiple

[The estimation of thyroxine, triiodothyronine, thyro-binding-index, and free-thyroxine-index in the newborn (author's transl)].

Because of the importance of early diagnosis of hypothyroidism normal values of thyroxine (T4), thyro-binding-index (TBI), free thyroxine-index (FTI) and triiodothyronine (T3) in the serum of newborns were established. In extremely premature babies as in early fetal life the total thyroxine is relatively low. The lowest serum thyroxine in newborns without hypothyroidism was found in a premature infant with a birth weight of 750 g, i.e. 4.8 mug/100 ml on the 4th day of life. Otherwise the T4 values were quite high during the neonatal period, without signs of hyperthyroidism. Our hypothyroid patients scarcely had higher T4 values (0.8-5.1 mug/100 ml) within the first month of life than older hypothyroid patients. Healthy newborns had a mean T4 value of about 15 mug/100 ml during the first week of life (two standard deviations 6.4-23.6 mug/100 ml). Afterwards the T4 values slowly came down to a mean of about 12 mug/100 ml in the 4th week of life. During the first month of life the FTI of hypothyroid patients was below two standard deviations of normal newborn values, whereas TBI-values showed an overlap. During the first 3 days of life newborns with goiter had T4-values in the lower normal or hypothyroid range without obvious signs of hypothyroidism. FTI was quite low, too, and TBI relatively high (as in hypothyroidism). Within the second week of life all these values normalized mostly after treatment with KI ointment, occasionally without this treatment. Where these values did not normalize, hypohtyroidism was assumed. Triiodothyronine in cord blood was very low (0.47 ng/1.6 ng/ml) during the neonatal period (one to two days after birth almost 2.0 mg/ml). Values in our hypothyroid patients fluctuated widely (zero to slightly elevated values with a mean of 0.78 ng/ml). Therefore, T4 seemed more reliable than T3 for the diagnosis of hypothyroidism (the opposite was true for hyperthyroidism.

Fetal Blood

[Therapy with an antibiotic combination mezlocillin/oxacillin and clinical experience/Second communication: Children (author's transl)].

Almost all infections of newborn have to be treated with antibiotics before the result of microbiological examination is available since there are either difficulties in identifying the causative organisms(s) or antibiotic treatment must be instituted without delay in view of the patient's life threatening condition. The present paper reports on the therapeutic results obtained in association with the multicentre study of 51 children affected by bacterial infections. 17 (33.0%) patients were newborn up to one week of age. 12 patients were classified as premature babies, some presenting a high degree of immaturity. Treatment with Optocillin (Bay 1-1330), a combination of 6-((R)-2-[3-Methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido)-penicillanic acid sodium salt (mezlocillin, Baypen) and 5-methyl-3-phenyl-4-isoxazolyl-penicillin (oxacillin, Stapenor), proved effective in 90% of the children, although 22 patients had been treated with other antibiotics prior to the use of this compound. An average daily dose of about 225 mg/kg bodyweight was found to be effective and perfectly tolerated even on long-term treatment, as became evident from two cases of extremely premature babies effected by neonatal septicaemia (duration of treatment 38 and 34 days, respectively). The combination showed a perfect local tolerance, exanthema appearing only in one infant.

Adolescent

Theophylline pharmacokinetics in premature infants with apnea.

The pharmacokinetics of theophylline were examined in eight low-birth-weight infants (gestation: 26-32 weeks: birth-weight: 887-1,480 gm), who received the drug for treatment of primary apnea. The drug was assayed by high pressure liquid chromatography. The final dosage was 1 to 3 mg/kg/6 hour at 25 to 37 days of age. At the time, theophylline had a prolonged half-life ranging from 13 to 29 hours, a relatively large volume of distribution of 0.65 to 2.86 1/kg, and a small body clearance of 23 to 68 ml/hr/kg. The extremely slow and variable elimination of theophylline must be considered in treatment of apneic infants. The initial dosage regimen suggested is a loading dose of 6 mg/kg and a maintenance dose of 2 mg/kg/ 12 hours, with adjustments made based on monitoring of the serum concentration and on an increased biotransformation capability as maturation occurs.

Apnea

Test strip meconium screening for cystic fibrosis.

The Boehringer-Mannheim Corporation (BMC) strip test is extremely reliable in indicating an albumin content above 20 mg/gm of dried meconium. All infants born during one year in 14 Milwaukee area hospitals were tested. Of 16,224 newborns, two were diagnosed correctly as suffering from cystic fibrosis and two were missed. False-positive tests were obtained in 0.9% of infants (prematurity, melena, gastroschisis, and intrauterine infection). The strip test is, at present, the best available but not the perfect screening method for cystic fibrosis.

Albumins