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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeine therapy reduces apnea of prematurity, promotes successful extubation from invasive positive-pressure ventilation, and decreases the incidence of bronchopulmonary dysplasia. The recommended dosing for caffeine is a loading dose of 20 mg/kg followed by a 5 mg/kg/d maintenance dose. However, controversy exists about the optimal dosing regimen and data on serum caffeine concentrations in extremely immature infants are scant. We determined serum caffeine concentrations approximately 7 days after starting therapy with a 20 or 25 mg/kg loading dose and a 6 mg/kg/d maintenance dose in 154 infants with a mean gestational age of 29 weeks. The 25th to 75th percentile range for the serum caffeine concentrations with the two dosing regimens was equivalent, approximately 18 to 23 mg/L. Within the first 14 postnatal days, the serum caffeine concentrations were not dependent on postmenstrual age, weight, or postnatal age, and were in a range that is safe and therapeutic. This latter observation remained valid over the ranges of clinical and laboratory assessments of renal and hepatic functions that are usually found in practice. Routine measurement of steady-state serum caffeine concentrations in infants 24 to 35 weeks gestational age is not required in the absence of ongoing apnea/hypopnea or signs compatible with toxicity.
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PMID:Serum caffeine concentrations in preterm neonates. 1719 51

Postnatal caffeine treatment of rats can influence brain excitability during development. To study the mechanism involved in the alterations of seizure susceptibility, we used an animal model that corresponds to the infants treated with caffeine for apnea of prematurity. Seizure susceptibility to four convulsant drugs (pentetrazol, picrotoxin, bicuculline and aminophylline) was assessed in 12- and 25-day-old rats exposed to caffeine at a daily dose of 10 and/or 20 mg/kg s.c. at postnatal days 7-11. Our results demonstrated that the changes in generalized tonic-clonic seizures (GTCS) are more expressed than changes in minimal clonic seizures. There are marked differences among individual convulsants with the highest sensitivity of aminophylline-induced seizures and nearly complete resistance of bicuculline-induced seizures. The changes in individual models are age specific: aminophylline- and picrotoxin-induced seizures are more affected in 12- than in 25-day-old rats whereas PTZ-induced seizures are more changed by early postnatal caffeine exposure in 25- than in 12-day-old animal. Taken together, repeated caffeine treatment from postnatal day 7 to 11 reduces the seizure susceptibility during development and this reduction is also model specific.
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PMID:Effects of postnatal caffeine exposure on seizure susceptibility in developing rats. 1743 12

This article reports on a systematic review of studies on caffeine intake during pregnancy and prevalence of low birth weight and prematurity, focusing on methods to quantify intake and control for confounding. The review consisted of an article search from 1996 to 2006 in MEDLINE, LILACS, and PubMed, using the key words: "caffeine", "coffee", "low birth weight", "birth weight", "preterm", "premature", and "prematurity". Ten articles were selected. Methods used to quantify caffeine consumption were: semi-quantitative food frequency questionnaires for diet or only caffeinated products, including one self-applied questionnaire; food recall; questions on type and method of preparation; analysis of samples; and urine and plasma caffeine levels. In three studies, high caffeine consumption was associated with low birth weight and/or prematurity. Contradictions between studies may be due to difficulties in measuring caffeine consumption; assessment of different caffeine sources; variations in the mode of preparation and amount consumed; and sample size. Association between moderate caffeine consumption and fetal growth was not demonstrated, so a more precise measurement of caffeine intake is necessary.
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PMID:[Caffeine consumption during pregnancy and prevalence of low birth weight and prematurity: a systematic review]. 1815 23

Caffeine is widely used to treat apneas of prematurity during the neonatal period; however, the potential consequences of administering a neonatal caffeine treatment (NCT) during a critical period for respiratory control development are unknown. The present study therefore determined whether NCT in rats alters the hypoxic respiratory chemoreflex measured at adulthood. Newborn rats received either caffeine (15 mg/kg) or water (control) each day from postnatal day 3 to 12. The ventilatory response to a hypoxic challenge (inspired O(2) fraction = 0.12) was first evaluated in awake adult female and male rats using whole body plethysmography. Results showed that NCT increased the initial phase of the breathing frequency response to hypoxia in males only. This result was confirmed in anesthetized and artificially ventilated adult male rats where NCT also increased the phrenic burst frequency response to hypoxia. RT-PCR assessment of mRNA encoding for adenosine A(1A) and A(2A) receptors, dopamine D(2) receptors, and tyrosine hydroxylase in the rat carotid bodies showed that NCT enhanced mRNA expression levels of adenosine A(2A), dopamine D(2) receptors, and tyrosine hydroxylase of males but not females. Subsequent experiments on awake male rats showed that injection of the adenosine A(2A) receptor antagonist ZM2413855 (1 mg/kg ip) before ventilatory measurements abolished, in NCT rats, the enhanced respiratory frequency response observed during the early phase of hypoxia. We propose that NCT elicits a sex-specific increase in the hypoxic respiratory chemoreflex, which is related, at least partially, to an enhancement in adenosine A(2A) receptors in the rat carotid body.
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PMID:Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats. 1859 10

Caffeine is an adenosine receptor antagonist that is commonly used in the clinic as a respiratory stimulant to treat apnea of prematurity. A recent clinical study showed that newborns treated with caffeine present no neuro-developmental disabilities at 2 years of age in comparison to placebo-treated children [Schmidt, B., Roberts, R.S., Davis, P., Doyle, L.W., Barrington, K.J., Ohlsson, A., Solimano, A., Tin, W., 2007. Long-term effects of caffeine therapy for apnea of prematurity. N. Engl. J. Med. 357, 1893-1902]. Although neonatal caffeine administration in this population is associated with clear short- and long-term health improvements, the consequences of this treatment on basic homeostatic functions such as respiratory regulation are unknown. This article reviews evidence indicating that neonatal caffeine treatment modifies respiratory control development and that these changes persist until adulthood. The mechanisms contributing to this form of developmental plasticity are unknown but current data indicate that caffeine treatment, especially during the perinatal period, alters adenosinergic neuromodulation of the respiratory control system. While human data show that neonatal caffeine treatment is relatively safe for some aspects of neural development, the results obtained in animal studies raise important questions pertaining to the potential long-term effects of this treatment on the respiratory control system.
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PMID:Adenosinergic modulation of respiratory activity: developmental plasticity induced by perinatal caffeine administration. 1870 76

Caffeine is a common treatment for apnea of prematurity. Although relatively safe, little is known about the potential long-term effects of this treatment on respiratory control development. We previously showed that adult male (but not female) rats previously subjected to neonatal caffeine treatment (NCT; 15 mg/kg/day, postnatal days 3-12) show a higher breathing frequency response during the early phase of hypoxic exposure. To address the role of sexual hormones in this sexual dimorphism, the present study tested the hypothesis that in adult male rats, circulating testosterone contributes to NCT-related augmentation of the acute breathing frequency response to hypoxia. Whole body plethysmography was used to compare the acute ventilatory response to moderate hypoxia (FIO2=0.12; 20 min) between rats previously subjected to NCT or neonatal water treatment (NWT; same treatment as NCT but using water). In each group, rats were either sham-operated or gonadectomized (GDX) 14 days prior to ventilatory measurements. In sham-operated rats, the increase in breathing frequency measured during the first 8 min of hypoxia was greater in NCT rats versus NWT. The hypoxic ventilatory response measured at the end of the hypoxia was not affected by treatment, thus indicating that NCT mainly affected the peripheral component of the chemoreflex. Gonadectomy had no effect on NCT but augmented the frequency response of NWT rats to the same level of NCT, thus eliminating the between-group difference. NCT may interfere with the inhibitory effect of circulating testosterone on carotid body function. Although appealing, additional experiments are necessary to substantiate this interpretation.
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PMID:Enhancement of the breathing frequency response to hypoxia by neonatal caffeine treatment in adult male rats: the role of testosterone. 1904 35

Caffeine, a nonspecific adenosine receptor (AR) antagonist is widely used to treat apnea of prematurity. Because adenosine modulates multiple biologic processes including inflammation, we hypothesized that AR blockade by caffeine would increase cytokine release from neonatal monocytes. Using cord blood monocytes (CBM), we investigated 1) the changes in AR mRNA profile by real time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and protein expression (western blot) after in vitro culture, caffeine or lipopolysaccharide (LPS) exposure, and 2) the modulation of cytokine release and cyclic adenosine monophosphate (cAMP) production by enzyme-linked immunosorbent assay (ELISA) induced by caffeine and specific AR antagonists: DPCPX(A1R), ZM241385(A2aR), MRS1754(A2bR), and MRS1220(A3R). After 48 h in culture, A2aR and A2bR gene expression increased 1.9 (p = 0.04) and 2.5-fold (p = 0.003), respectively. A1R protein expression directly correlated with increasing LPS concentrations (p = 0.01), with minimal expression preexposure. Only caffeine (50 microM) and DPCPX (10 nM) decreased tumor necrosis factor-alpha (TNF-alpha) release from LPS activated-CBM by 20 and 25% (p = 0.01) and TNF-alpha gene expression by 30 and 50%, respectively, in conjunction with a > or =2-fold increase in cAMP (p < 0.05). AR blockade did not modulate other measured cytokines. The induction of A1R after LPS exposure suggests an important role of this receptor in the control of inflammation in neonates. Our findings also suggest that caffeine, via A1R blockade, increases cAMP production and inhibits pretranscriptional TNF-alpha production by CBM.
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PMID:Caffeine modulates TNF-alpha production by cord blood monocytes: the role of adenosine receptors. 1904 57

The objective of this study was to develop a population model of the pharmacokinetics (PK) of caffeine after orogastric or intravenous administration to extremely premature neonates with apnea of prematurity who were to undergo extubation from ventilation. Infants of gestational age <30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d. Four blood samples were drawn at prerandomized times from each infant during caffeine treatment. Serum caffeine was assayed by enzyme-multiplied immunoassay technique. Concentration data (431 samples, median: 4 per subject) were obtained from 110 (52 male) infants of mean birth weight of 1009 g, current mean weight (WT) of 992 g, mean gestational age of 27.6 weeks, and mean postnatal age (PNA) of 12 days. Of 1022 doses given, 145 were orogastric, permitting estimation of absolute bioavailability. A 1-compartment model with first-order absorption was fitted to the data in NONMEM. Patient characteristics were screened (P < 0.01) in nested models for pharmacokinetic influence. Model stability was assessed by nonparametric bootstrapping. Clearance (CL) increased nonlinearly with increasing PNA, whereas volume of distribution (Vd) increased linearly with WT, according to the following allometric models: CL (L/h) = 0.167 (WT/70) (PNA/12); Vd (L) = 58.7 (WT/70). The mean elimination half-life was 101. Interindividual variability (IIV) of CL and Vd was 18.8 % and 22.3 %, respectively. Interoccasion variability (IOV) of CL and Vd was 35.1% and 11.1%, respectively. This study established that the elimination of caffeine was severely depressed in extremely premature infants but increased nonlinearly after birth up to age 6 weeks. Caffeine was completely absorbed, which has favorable implications for switching between intravenous and orogastric routes. The interoccasion variability about CL was twice the interindividual variability, which, among other factors, indicates that routine serum concentration monitoring of caffeine in these patients is not warranted.
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PMID:Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. 1905 73

Two approaches were taken to determine what is new and where we are going in terms of outcomes for the extremely premature infant: publications from 2004 to 2007 were reviewed, and the 30-year outcome at the authors' institutions was assessed. Recent literature documents improving early childhood outcomes in the face of improved survival. Childhood cerebral palsy prevalence rates have been reported to be as low as 19 per 1000 live births for infants born at 20-27 weeks gestation. Vision and hearing loss have been reported in fewer than 1% of survivors. The rate of overall intellectual impairment has not improved, although impairment was reduced in a recent trial of caffeine therapy for apnea of prematurity, and this remains an important area for study. In sum, recent findings herald a more positive perspective on the outcome for extremely premature survivors. It can thus be expected that new intensive-care trials will attempt to reduce the proportion of survivors with adverse outcomes. Childhood assessments will have a greater focus on function and participation. Information on improved outcomes for preterm infants will inform guidelines of decision making used to help parents to determine what is best for their child. The audit component of follow-up studies will expand and more cohort and trial studies will become multicenter, national, and international.
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PMID:Outcomes for the extremely premature infant: what is new? And where are we going? 1921 32

Considerable effort has been devoted to the development of strategies to reduce the incidence of bronchopulmonary dysplasia (BPD), including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent BPD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia, were evaluated for the improvement of other outcomes and found to reduce BPD. Cohort studies suggest that the use of continuous positive airway pressure as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce BPD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7-11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease.
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PMID:Prevention of bronchopulmonary dysplasia. 1973 53


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