Adverse effect of maternal caffeine ingestion on fetal cerebrum in rat

Tanaka, Harumi; Nakazawa, Kazuharu; Arima, Masataka

doi:10.1016/s0387-7604(83)80045-x

Cited by 31 publications

(14 citation statements)

References 24 publications

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“…Many studies have been per formed on the effects of maternal caffeine ingestion on various reproductive, terato genic and developmental characteristics in rats [1,2] and humans [3,4], However, even now, whether or not and if so how maternal caffeine ingestion is a risk factor in the de velopment of offspring is a matter of discus sion. In a previous study we demonstrated the adverse effect of maternal caffeine inges tion on the fetal cerebrum in the rat, which may be associated with the decreased appar ent volume of distribution of caffeine in ma ternal plasma and the high caffeine content of fetal cerebrum [5][6][7]. In the present study a low level of maternal caffeine consumption was maintained and an attempt was made to elucidate the factors related to cerebral func tion.…”

supporting

confidence: 47%

“…To our knowledge, these phenomena were not recognized in previously docu mented studies. In our pregnant rats, 0.04 and 0.02% caffeine intakes were calculated to correspond approximately to less than 50 and 25 mg caffcine/kg body weight/day, re spectively, because the consumed volume measurements were rough [5,6], When the maternal and fetal caffeine levels in the morning on gestational day 21 in the present study were compared with those in the eve ning on gestational day 20 in the previous study [5], it was considered that these levels were maintained at least during middle to late pregnancy. Therefore, an adverse effect of maternal caffeine on the fetal cerebrum is possible with a level of 1.5-3.0 jig caffeine/ml in maternal plasma, this concentra tion coinciding with that found on random plasma caffeine measurement in 600 adult outpatients [10].…”

Section: Discussionmentioning

confidence: 98%

“…The experimental procedures used for the prepa ration of fetal models were essentially as described previously [5,6], Virgin female albino rats of the Wistar strain were divided into caffeine (1,3,7-trimethylxanthine; Wako Chemical Industries Ltd., Osaka, Ja pan) and control groups, receiving 0.04% caffeine (C) or 0.02 % caffeine (c) via drinking water, and drinking water only (W), respectively. The groups are desig nated as follows; W or c before mating -W or C (c) during pregnancy.…”

Section: Methodsmentioning

confidence: 99%

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Effects of Maternal Caffeine Ingestion on the Perinatal Cerebrum

Tanaka¹,

Nakazawa²,

Arima³

1987

Neonatology

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The cerebra of fetal rats from dams given 0.04 or 0.02% caffeine in drinking water ad libitum before and/or during pregnancy were examined on gestational day 21. A low placental weight was induced by caffeine ingestion for a long time throughout premating and pregnancy. A greater reduction in the fetal weight of the cerebrum than that of the body was observed with caffeine ingestion during pregnancy of levels of 1.5–3.0 μg caffeine/ml or g wet weight in dams and fetuses. In the cerebra of offspring, the levels of caffeine and theophylline did not change for 4 h after birth, and theophylline was not detected at all after intraperitoneal injection of caffeine. Thus, maternal caffeine should be warned against the fetal cerebral function.

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supporting

confidence: 47%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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Effects of Maternal Caffeine Ingestion on the Perinatal Cerebrum

Tanaka¹,

Nakazawa²,

Arima³

1987

Neonatology

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“…DNA content in the caffeine-supple mented group during gestation and lactation periods showed no difference from the con trol group. The DNA content of the fetal cer ebrum when dams are given caffeine through drinking water during gestation [31] and that of the developing brain of the suckling pups whose dams are given a caffeine-supple mented diet [3] also showed no difference from the control. In contrast, the DNA con tent in the caffeine plus zinc group was higher than that of the control group.…”

Section: Discussionmentioning

confidence: 93%

Interaction between Caffeine and Zinc on Brain in Newborn Rats

Nakamoto

Joseph²

1991

Neonatology

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The purpose of this study was to determine whether adding zinc to the caffeine-supplemented diet of dams during gestation and lactation would affect brain development in newborn rats. On day 9 of gestation, dams of group 1 were fed a 20% protein diet as a control. Dams of group 2 were fed a 20% protein diet supplemented with caffeine. Dams of group 3 were fed a 20% protein diet supplemented with caffeine and zinc. The amount of caffeine added to the maternal diet was 2 mg/100 g of body weight. The amount of zinc chloride added to diet was 0.6 g/kg of diet. At birth, 8 randomly selected pups from each group were assigned to each dam of the respective group and were continuously fed the same diet. On day 15, the pups were killed and brains were removed. Zinc, protein, DNA, alkaline phosphatase activity and cholesterol contents were measured. Milk and maternal and neonatal blood were collected to determine caffeine levels. There was a significant correlation between the milk caffeine and brain caffeine concentrations in group 3. A significant correlation between the neonatal plasma caffeine and brain caffeine concentrations was observed in groups 2 and 3. There was no correlation between neonatal brain weight and zinc content per brain in each group. The correlation between neonatal brain weight and alkaline phosphatase activity was significant in groups 1 and 3. The neonatal zinc content and concentration of group 2 was less than that of group 1. The DNA content and concentration of group 3 was greater than that of either groups 1 or 2. Supplementation of zinc to the caffeine-added diet could restore the brain zinc levels observed in brains of newborn rats.

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“…Therefore, a correction factor relative to the metabolic body weight for the dose must be applied for comparing caffeine administration (2,7). In this context, Tanaka et al (6) demonstrated that a dose of caffeine of 70 mg⅐kg Ϫ1 ⅐d Ϫ1 ingested by pregnant rats is equivalent to a dose of~30 mg⅐kg Ϫ1 ⅐d Ϫ1 for humans. They also concluded that a dose of caffeine comparable to what is used in this study (49 mg⅐kg Ϫ1 ⅐d Ϫ1 ) is in the moderate range for a human model.…”

Section: General Observationsmentioning

confidence: 99%

Consequences of In Utero Caffeine Exposure on Respiratory Output in Normoxic and Hypoxic Conditions and Related Changes of Fos Expression: A Study on Brainstem-Spinal Cord Preparations Isolated From Newborn Rats

et al. 2003

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Several aspects of the central regulation of respiratory control have been investigated on brainstem-spinal cord preparations isolated from newborn rats whose dam was given 0.02% caffeine in water as drinking fluid during the whole period of pregnancy. Analysis of the central respiratory drive estimated by the recording of C4 ventral root activity was correlated to Fos pontomedullary expression. Under normoxic conditions, preparations obtained from the caffeine-treated group of animals displayed a higher respiratory frequency than observed in the control group (9.2 Ϯ 0.5 versus 7.2 Ϯ 0.6 burst/min). A parallel Fos detection tends to indicate that the changes of the respiratory rhythm may be due to a decrease in neuronal activity of medullary structures such as the ventrolateral subdivision of the solitary tract, the area postrema, and the nucleus raphe obscurus. Under hypoxic conditions, the preparations displayed a typical hypoxic respiratory depression associated with changes in the medullary Fos expression pattern. In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine. Taken together, these results support the idea that in utero caffeine exposure could affect central respiratory control. Caffeine, which belongs to the methylxanthine family, is commonly ingested in various beverages such as coffee, tea, or cola drink (1). It interacts with adenosine neuronal transmitter system as an A 1 and A 2A receptor antagonist (2) and has been shown to alter the adenosinergic transmission upon chronic administration (3-5).In rats, a positive correlation has been established between exposure to caffeine during gestation and a reduction of the fetal cerebral weight (6). Such an observation could lead to propose that caffeine modifies maturational neuronal processes. Moreover, various studies reported that a sustained maternal caffeine intake induces harmful physiologic effects on human newborns (for review, see 7). Among these effects, respiratory perturbations have been described (8 -10). Nevertheless, the existence of a relation between exposure to caffeine during pregnancy and the occurrence of respiratory perturbations in

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Adverse effect of maternal caffeine ingestion on fetal cerebrum in rat

Cited by 31 publications

References 24 publications

Effects of Maternal Caffeine Ingestion on the Perinatal Cerebrum

Effects of Maternal Caffeine Ingestion on the Perinatal Cerebrum

Interaction between Caffeine and Zinc on Brain in Newborn Rats

Consequences of In Utero Caffeine Exposure on Respiratory Output in Normoxic and Hypoxic Conditions and Related Changes of Fos Expression: A Study on Brainstem-Spinal Cord Preparations Isolated From Newborn Rats

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