Previous clinical studies have shown that caffeine consumption during pregnancy is linked with lower birth weights, but new research in rats, reported by scientists at Wuhan University, China, now suggests that consuming an amount of caffeine equivalent to 2–3 cups of coffee per day during pregnancy may also impair fetal liver development and increase the risk that offspring will develop liver disease in adulthood. The study found that rat pups exposed to caffeine during pregnancy (prenatal caffeine exposure; PCE) had lower levels of the liver hormone insulin-like growth factor (IGF1), and higher levels of the stress hormone corticosteroid, at birth. Liver development after birth then went through a compensatory “catch up” phase, which was characterized by increased levels of IGF1.

“Our results indicate that prenatal caffeine causes an excess of stress hormone activity in the mother, which inhibits IGF1 activity for liver development before birth,” commented Yinxian Wen, PhD, co-author of the team’s published study in the Journal of Endocrinology. “However, compensatory mechanisms do occur after birth to accelerate growth and restore normal liver function, as IGF1 activity increases and stress hormone signaling decreases. The increased risk of fatty liver disease caused by prenatal caffeine exposure is most likely a consequence of this enhanced, compensatory postnatal IGF1 activity.” The researchers, headed by Hui Wang, PhD, reported their results in a paper titled, “Prenatal caffeine exposure induces liver developmental dysfunction in offspring rats.”

Caffeine is one of the most frequently ingested psychoactive substances worldwide, the authors wrote. And while caffeine consumption during pregnancy is common, studies in pregnant women have indicated that an intake of 300 mg/day or more, which is equivalent to about 2 to 3 cups coffee, is associated with lower infant birth weight. Research in rats by the Wuhan University team had also shown that PCE holds back fetal growth rate (intrauterine growth retardation), and is associated with high offspring susceptibility to non-alcoholic fatty liver disease (NAFLD), a condition that is normally associated with obesity and diabetes. Their studies indicated that underlying mechanisms are linked with fetal overexposure to maternal glucocorticoids.

“Studies have indicated that caffeine can elevate the levels of glucocorticoids in both humans and animals,” the investigators wrote. “High levels of glucocorticoids inhibit the expression of IGF1 in various tissues and cells. Research also indicates that IGF1 is the major mediator of prenatal and postnatal growth,” the researchers pointed out. “Previous studies have reported that glucocorticoids play vital roles in the regulation of fetal growth, development, and maturation and are also important factors in metabolic syndrome in adulthood.”

Their previous work had also found that PCE increased the susceptibility of offspring to metabolic syndrome under conditions of chronic stress, or high-fat diet feeding. “However, whether PCE-induced liver developmental dysfunction continues after birth, whether PCE possesses intrauterine programming alteration properties and the underlying molecular mechanisms are not yet known,” the team wrote. The latest studies aimed to verify whether PCE disrupts liver development before and after birth, and evaluate possible mechanisms in more detail. The Wuhan University researchers evaluated the effects of low (equivalent to 2–3 cups of coffee) and high (equivalent of 6–9 cups of coffee) doses of caffeine, given to pregnant rats, on liver function and hormone levels of their offspring.

The results showed that maternal caffeine consumption was associated with reduced fetal weights and increased IUGR rates, in parallel with dysfunction in fetal liver development, increased fetal serum corticosterone levels, and lower IGF1 levels. Gene expression analyses also found that impacted on liver development genes. “Analysis of development-related genes in the fetal liver showed decreased expression of development-promoting genes (such as PCNA, HFN4α, ALB) and enhanced expression of development-suppressing genes (such as caspse-3, AFP). These results suggested that PCE induces liver development toxicity in fetal rats.” The PCE offspring with IUGR exhibited rapid catch-up growth, “accompanied by a compensatory enhancement of liver structure and functional development.”

The authors conclude that their results point to maternal corticosterone overexposure inducing multiple gene expression changes in the fetal rat liver, accompanied by a reduction in total basal metabolic rate in the fetus which could then contribute to what is known as “thrifty phenotype” programing. “Thrifty phenotype programming is an initiative of multiple organ changes in the fetus, optimizing the use of reduced energy supplies to ensure survival,” the authors wrote. “In this study, we found that the fetal liver structure (decreased number of hepatocytes and Ki67 expression) and expression of fetal liver development-related genes (reduced development-promoting gene expression, increased development-suppressing gene expression) were altered induced by maternal corticosterone overexposure … This study not only clarified the molecular mechanisms of PCE-induced liver development toxicity but also provided an experimental and theoretical basis for addressing the susceptibility to adult metabolic syndrome and related metabolic diseases in PCE-induced IUGR offspring.”

The studies provide new insights into caffeine-related hormonal changes that may impact on birth weight and fetal liver development, and suggest potential mechanisms by which PCE offspring may be predisposed to liver disease later in life. The authors acknowledge that while their findings will need to be confirmed in humans, the results do indicate that expectant mothers may do well to steer clear of caffeine. “Our work suggests that prenatal caffeine is not good for babies and although these findings still need to be confirmed in people, I would recommend that women avoid caffeine during pregnancy,” Wen concluded.

This site uses Akismet to reduce spam. Learn how your comment data is processed.