Serum levels of caffeine in umbilical cord and apnea of prematurity

Hentges, Cláudia Regina; Guedes, Renata Rostirola; Silveira, Rita C.; Procianoy, Renato S.

doi:10.2223/jped.1990

Cited by 5 publications

(7 citation statements)

References 26 publications

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“…Since the 2006 publication of the results of caffeine therapy for AOP, caffeine has been routinely used in neonate care with the noted safety. Of note, plasma caffeine and metabolite levels in dams that we obtained in our study are 0.3 mg/L, which is consistent with earlier studies (32, 33) and comparable with regular human consumption (1.5 mg/L) (20), with reported umbilical cord plasma in the newborns of mothers who consumed coffee (0.5–2 mg/L) (54), and with the serum from breast‐fed infants and caffeine‐exposed mothers (0.25–3.2 mg/L) (48, 55)—all being, in fact, 10‐ to 20‐fold lower than caffeine levels achieved by caffeine treatment for AOP infants (~15 mg/L) (45, 46, 48, 49). Currently, caffeine treatment for AOP is usually initiated within the first 10 d of life in the preterm infant (56).…”

Section: Resultssupporting

confidence: 93%

“…Caffeine has a complex pharmacology, with multiple molecular targets. Caffeine at levels of 0.1 to 1.0 g/L in drinking water fed dams in this study can give plasma caffeine and metabolite levels in dams at the concentration of 0.2 to 1 mM (mg/L) (32,33), which is comparable with concentrations obtained from the umbilical cord plasma of newborns whose mothers consumed coffee [0.5-2 mM (mg/L)] (54) and in the serum of breast-fed infants of caffeine-exposed mothers (48,55). Among multiple molecular targets of caffeine, adenosine receptor blockade by caffeine occurs at concentrations (2-50 mM) that are 20-to 100-fold less than that required for phosphodiesterase or GABA A receptor inhibition and calcium release (.200 mM) (20,57).…”

Section: Caffeine Protects Against Oir By a 2a Rdependent And -Indepesupporting

confidence: 81%

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Caffeine preferentially protects against oxygen‐induced retinopathy

Zhang

Zhou

et al. 2017

FASEB j.

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Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and brain development of preterm infants. The clinical observation of reduced ROP severity in premature infants after caffeine treatment for apnea suggests that caffeine may protect against ROP. Here, we demonstrate that caffeine did not interfere with normal retinal vascularization development but selectively protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia-induced vaso-obliteration, which suggests a novel protection window by caffeine. At the hyperoxic phase, caffeine reduced oxygen-induced neural apoptosis by adenosine A receptor (AR)-dependent mechanism, as revealed by combined caffeine and AR-knockout treatment. At the hypoxic phase, caffeine reduced microglial activation and enhanced tip cell formation by AR-dependent and -independent mechanisms, as combined caffeine and AR knockout produced additive and nearly full protection against OIR. Together with clinical use of caffeine in neonates, our demonstration of the selective protection against OIR, effective therapeutic window, adenosine receptor mechanisms, and neuroglial involvement provide the direct evidence of the novel effects of caffeine therapy in the prevention and treatment of ROP.-Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y., Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L., Chen, J.-F. Caffeine preferentially protects against oxygen-induced retinopathy.

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Section: Resultssupporting

confidence: 93%

Section: Caffeine Protects Against Oir By a 2a Rdependent And -Indepesupporting

confidence: 81%

Caffeine preferentially protects against oxygen‐induced retinopathy

Zhang

Zhou

et al. 2017

FASEB j.

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“…For instance, a mean blood caffeine concentration of ∼ 22 µM was reported in pregnant women at 36 weeks of gestation [44], while a plasma concentration of 40 µM caffeine and 20 µM paraxanthine was observed in humans after ingestion of 250 mg of caffeine [45]. Recently, one study showed that plasma levels of caffeine were between 1–50 µM in umbilical cords of preterm newborns [46]. Thus, if these in vitro findings could be extrapolated to human pregnancies in vivo , they would suggest that caffeine might inhibit fetal growth at least in part by down-regulating placental 11β-HSD2 directly and/or indirectly through its major metabolite, paraxanthine.…”

Section: Discussionmentioning

confidence: 99%

Caffeine Reduces 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in Human Trophoblast Cells through the Adenosine A2B Receptor

et al. 2012

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Maternal caffeine consumption is associated with reduced fetal growth, but the underlying molecular mechanisms are unknown. Since there is evidence that decreased placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is linked to fetal growth restriction, we hypothesized that caffeine may inhibit fetal growth partly through down regulating placental 11β-HSD2. As a first step in examining this hypothesis, we studied the effects of caffeine on placental 11β-HSD2 activity and expression using our established primary human trophoblast cells as an in vitro model system. Given that maternal serum concentrations of paraxanthine (the primary metabolite of caffeine) were greater in women who gave birth to small-for-gestational age infants than to appropriately grown infants, we also studied the effects of paraxanthine. Our main findings were: (1) both caffeine and paraxanthine decreased placental 11β-HSD2 activity, protein and mRNA in a concentration-dependent manner; (2) this inhibitory effect was mediated by the adenosine A2B receptor, since siRNA-mediated knockdown of this receptor prevented caffeine- and paraxanthine-induced inhibition of placental 11β-HSD2; and (3) forskolin (an activator of adenyl cyclase and a known stimulator of 11β-HSD2) abrogated the inhibitory effects of both caffeine and paraxanthine, which provides evidence for a functional link between exposure to caffeine and paraxanthine, decreased intracellular levels of cAMP and reduced placental 11β-HSD2. Taken together, these findings reveal that placental 11β-HSD2 is a novel molecular target through which caffeine may adversely affect fetal growth. They also uncover a previously unappreciated role for the adenosine A2B receptor signaling in regulating placental 11β-HSD2, and consequently fetal development.

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“…13,14 Even though there are studies identifying a diversity of risks related to neonatal morbidity and mortality and high-incidence rates of prematurity-related sequelae of varied natures, both L-PTNB and their diversity of high risk when compared to TNB deserved our special consideration in this systematic review. 11,13,15 It is a well-known fact that the main cause of maternal death is complications caused by high blood pressure during pregnancy or at the time of delivery, as well as hemorrhages and other morbidities. 16,17 However, studies on birth weight and changes in arterial blood pressure throughout the child's life were more unanimous in investigating possible risks, especially when compared with studies on GA and current infant weight.…”

Section: Prematurity Outcomesmentioning

confidence: 99%

Dyslipidemia and maternal obesity: Prematurity and neonatal prognosis

Nascimento

Souza

Silva

et al. 2018

Rev. Assoc. Med. Bras.

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NascimeNto iB et al. 264Rev assoc med Objective: To identify the changes caused by dyslipidemia and obesity in pregnancy suggesting causes for premature birth, and the prognosis for the newborn. Method: Systematic review based on the Medline, Lilacs, Embase and Cochrane library databases between 1996 and 2016. The search for studies included the following keywords: "dyslipidemia, pregnancy, obesity, preterm birth." A protocol was programmed and a protocol for inclusion/exclusion of studies was implemented. Results: Of the 5,789 articles initially selected between March 1996 and July 2016, only 32 were in accordance with the established criteria. Of these, 28.12% discussed risk factors of prematurity; 37.50%, metabolic alterations and gestational dyslipidemia; 21.87%, dyslipidemic complications in preterm birth; and 12,50%, lipid metabolism, glycemic and placental transfer. Conclusion:There is a reduced adaptation of obese pregnant women to the metabolic changes of gestation. This favors dyslipidemic intercurrences in the mother, which, directly or indirectly, suggests the occurrence of premature births and high lipid transfer to the fetus. Therefore, preterm newborns, whose mothers were dyslipidemic during pregnancy, have greater risk of epicardial fat, both in early (first year of life) and in later (adult) phases of life.

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Serum levels of caffeine in umbilical cord and apnea of prematurity

Abstract: Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Cited by 5 publications

References 26 publications

Caffeine preferentially protects against oxygen‐induced retinopathy

Caffeine preferentially protects against oxygen‐induced retinopathy

Caffeine Reduces 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in Human Trophoblast Cells through the Adenosine A2B Receptor

Dyslipidemia and maternal obesity: Prematurity and neonatal prognosis

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