Skip to main content
SpringerLink
Log in

Prenatal alcohol exposure and offspring liver dysfunction: a systematic review and meta-analysis

  • Review
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Limited studies have reported the effect of prenatal alcohol exposure (PAE) on fetal liver development or liver dysfunction. The current review was conducted to systematically review published studies of PAE and liver dysfunction.

Methods

Pub Med, Embase and Web of Science database were searched using terms of “prenatal alcohol exposure” and “liver” or “fetal alcohol spectrum disease” and “liver”. The pooled effect size of alcohol exposure was assessed by Hedges’s g and 95 % confidence interval (CI) using fixed model or random model depending on the heterogeneity determined by Q test and I 2 statistic.

Results

A total of 23 studies were included. The results indicated that gestation alcohol exposure resulted in significant reduction of fetal body weight (Hedges’s g = −6.854 ± 1.149, 95 % CI −9.106 to −4.602, P < 0.001), but not fetal liver weight reduction (Hedges’s g = −0.076 ± 0.878, 95 % CI −1.799 to 1.647, P = 0.931). PAE resulted in significant decline in protein synthesis or enzyme activity of offspring fetal liver including glutathione and 25(OH)2D (Hedges’s g = −1.149 ± 0.108, 95 % CI −1.361 to −0.938, P < 0.001), as well as significant increase in proteins including oxidants and collagen (Hedges’s g = 1.330 ± 0.146, 95 % CI 1.044–1.616, P < 0.001).

Conclusion

These results suggested that PAE affects fetal body weight but not liver weight, and that PAE may result in offspring fetal liver dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pan B, Zhu J, Lv T, Sun H, Huang X, Tian J (2014) Alcohol consumption during gestation causes histone3 lysine9 hyperacetylation and an alternation of expression of heart development-related genes in mice. Alcohol Clin Exp Res 38(9):2396–2402. doi:10.1111/acer.12518

    Article  CAS  PubMed  Google Scholar 

  2. Gil-Mohapel J, Titterness AK, Patten AR, Taylor S, Ratzlaff A, Ratzlaff T et al (2014) Prenatal ethanol exposure differentially affects hippocampal neurogenesis in the adolescent and aged brain. Neuroscience 273:174–188. doi:10.1016/j.neuroscience.2014.05.012

    Article  CAS  PubMed  Google Scholar 

  3. Sozo F, Dick AM, Bensley JG, Kenna K, Brien JF, Harding R et al (2013) Alcohol exposure during late ovine gestation alters fetal liver iron homeostasis without apparent dysmorphology. Am J Physiol Regul Integr Comp Physiol 304(12):R1121–R1129. doi:10.1152/ajpregu.00479.2012

    Article  CAS  PubMed  Google Scholar 

  4. Yao XH, Nguyen HK, Nyomba BL (2013) Prenatal ethanol exposure causes glucose intolerance with increased hepatic gluconeogenesis and histone deacetylases in adult rat offspring: reversal by tauroursodeoxycholic acid. PLoS One 8(3):e59680. doi:10.1371/journal.pone.0059680 (PubMed PMID: 23544086; PubMed Central PMCID: PMC3609812)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. doi:10.1371/journal.pmed.1000097 (PubMed PMID: 19621072; PubMed Central PMCID: PMC2707599)

    Article  PubMed  PubMed Central  Google Scholar 

  6. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  7. Milne M, Baran DT (1985) Inhibitory effect of maternal alcohol ingestion on rat pup hepatic 25-hydroxyvitamin D production. Pediatr Res 19(1):102–104. doi:10.1203/00006450-198501000-00027

    Article  CAS  PubMed  Google Scholar 

  8. Witek-Janusek L (1986) Maternal ethanol ingestion: effect on maternal and neonatal glucose balance. Am J Physiol 251(2 Pt 1):E178–E184

    CAS  PubMed  Google Scholar 

  9. Harris JE (1990) Hepatic glutathione, metallothionein and zinc in the rat on gestational day 19 during chronic ethanol administration. J Nutr 120(9):1080–1086

    CAS  PubMed  Google Scholar 

  10. Reyes E, Ott S, Robinson B (1993) Effects of in utero administration of alcohol on glutathione levels in brain and liver. Alcohol Clin Exp Res 17(4):877–881

    Article  CAS  PubMed  Google Scholar 

  11. Mauceri HJ, Lee WH, Conway S (1994) Effect of ethanol on insulin-like growth factor-II release from fetal organs. Alcohol Clin Exp Res 18(1):35–41

    Article  CAS  PubMed  Google Scholar 

  12. Burdge GC, Postle AD (1995) Effect of maternal ethanol consumption during pregnancy on the phospholipid molecular species composition of fetal guinea-pig brain, liver and plasma. Biochim Biophys Acta 1256(3):346–352

    Article  PubMed  Google Scholar 

  13. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ (1996) Mitochondrial dysfunction after fetal alcohol exposure. Alcohol Clin Exp Res 20(6):1029–1032

    Article  CAS  PubMed  Google Scholar 

  14. Addolorato G, Gasbarrini A, Marcoccia S, Simoncini M, Baccarini P, Vagni G et al (1997) Prenatal exposure to ethanol in rats: effects on liver energy level and antioxidant status in mothers, fetuses, and newborns. Alcohol 14(6):569–573

    Article  CAS  PubMed  Google Scholar 

  15. Renau-Piqueras J, Guasch R, Azorin I, Segui JM, Guerri C (1997) Prenatal alcohol exposure affects galactosyltransferase activity and glycoconjugates in the Golgi apparatus of fetal rat hepatocytes. Hepatology 25(2):343–350. doi:10.1002/hep.510250215

    Article  CAS  PubMed  Google Scholar 

  16. La Grange L, Wang M, Watkins R, Ortiz D, Sanchez ME, Konst J et al (1999) Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver. J Ethnopharmacol 65(1):53–61

    Article  PubMed  Google Scholar 

  17. Edwards J, Grange LL, Wang M, Reyes E (2000) Fetoprotectivity of the flavanolignan compound siliphos against ethanol-induced toxicity. Phytother Res 14(7):517–521

    Article  CAS  PubMed  Google Scholar 

  18. Robinson RS, Seelig LL Jr (2002) Effects of maternal ethanol consumption on hematopoietic cells in the rat fetal liver. Alcohol 28(3):151–156

    Article  CAS  PubMed  Google Scholar 

  19. Garcia-Rodriguez S, Arguelles S, Llopis R, Murillo ML, Machado A, Carreras O et al (2003) Effect of prenatal exposure to ethanol on hepatic elongation factor-2 and proteome in 21 day old rats: protective effect of folic acid. Free Radic Biol Med 35(4):428–437

    Article  CAS  PubMed  Google Scholar 

  20. Chen L, Zhang T, Nyomba BL (2004) Insulin resistance of gluconeogenic pathways in neonatal rats after prenatal ethanol exposure. Am J Physiol Regul Integr Comp Physiol 286(3):R554–R559. doi:10.1152/ajpregu.00076.2003

    Article  CAS  PubMed  Google Scholar 

  21. Azorin I, Portoles M, Marin P, Lazaro-Dieguez F, Megias L, Egea G et al (2004) Prenatal ethanol exposure alters the cytoskeleton and induces glycoprotein microheterogeneity in rat newborn hepatocytes. Alcohol Alcohol 39(3):203–212

    Article  CAS  PubMed  Google Scholar 

  22. Nammi S, Dembele K, Nyomba BL (2007) Increased 11beta-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero. Am J Physiol Regul Integr Comp Physiol 292(3):R1101–R1109. doi:10.1152/ajpregu.00255.2006

    Article  CAS  PubMed  Google Scholar 

  23. Yao XH, Nyomba BL (2008) Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring. Am J Physiol Regul Integr Comp Physiol 294(6):R1797–R1806. doi:10.1152/ajpregu.00804.2007

    Article  CAS  PubMed  Google Scholar 

  24. Ojeda ML, Vazquez B, Nogales F, Murillo ML, Carreras O (2009) Ethanol consumption by Wistar rat dams affects selenium bioavailability and antioxidant balance in their progeny. Int J Environ Res Public Health 6(8):2139–2149. doi:10.3390/ijerph6082139 (PubMed PMID: 19742151; PubMed Central PMCID: PMC2738878)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hewitt AJ, Walker KR, Kobus SM, Poklewska-Koziell M, Reynolds JN, Brien JF (2010) Differential effects of chronic ethanol exposure on cytochrome P450 2E1 and the hypothalamic-pituitary-adrenal axis in the maternal-fetal unit of the guinea pig. Neurotoxicol Teratol 32(2):164–170. doi:10.1016/j.ntt.2009.12.002

    Article  CAS  PubMed  Google Scholar 

  26. Murillo-Fuentes ML, Artillo R, Ojeda ML, Murillo ML, Carreras O (2010) Different effects on zinc redistribution if ethanol is consumed before or immediately after birth. J Trace Elem Med Biol 24(3):200–206. doi:10.1016/j.jtemb.2009.12.002

    Article  CAS  PubMed  Google Scholar 

  27. Drever N, Yin H, Kechichian T, Costantine M, Longo M, Saade GR et al (2012) The expression of antioxidant enzymes in a mouse model of fetal alcohol syndrome. Am J Obstet Gynecol 206(4):358 e19–358 e22. doi:10.1016/j.ajog.2012.01.017 (PubMed PMID: 22365038; PubMed Central PMCID: PMC3433754)

    Article  PubMed  Google Scholar 

  28. Hill AJ, Drever N, Yin H, Tamayo E, Saade G, Bytautiene E (2014) The role of NADPH oxidase in a mouse model of fetal alcohol syndrome. Am J Obstet Gynecol 210(5):466 e1–466 e5. doi:10.1016/j.ajog.2013.12.019 (PubMed PMID: 24334207; PubMed Central PMCID: PMC4011987)

    Article  PubMed  Google Scholar 

  29. Chavez GF, Cordero JF, Becerra JE (1988) Leading major congenital malformations among minority groups in the US, 1981–1986. MMWR CDC Surveill Summ 37(3):17–24

    CAS  PubMed  Google Scholar 

  30. Morales A, Garcia-Ruiz C, Miranda M, Mari M, Colell A, Ardite E et al (1997) Tumor necrosis factor increases hepatocellular glutathione by transcriptional regulation of the heavy subunit chain of gamma-glutamylcysteine synthetase. J Biol Chem 272(48):30371–30379

    Article  CAS  PubMed  Google Scholar 

  31. Harbrecht BG, Di Silvio M, Chough V, Kim YM, Simmons RL, Billiar TR (1997) Glutathione regulates nitric oxide synthase in cultured hepatocytes. Ann Surg 225(1):76–87 (PubMed PMID: 8998123; PubMed Central PMCID: PMC1190609)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wong YC, Tay SS, McCaughan GW, Bowen DG, Bertolino P (2015) Immune outcomes in the liver: is CD8 T cell fate determined by the environment? J Hepatol. doi:10.1016/j.jhep.2015.05.033

    Google Scholar 

  33. Szabo G, Petrasek J (2015) Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol 12(7):387–400. doi:10.1038/nrgastro.2015.94

    Article  CAS  PubMed  Google Scholar 

  34. Maraslioglu M, Oppermann E, Blattner C, Weber R, Henrich D, Jobin C et al (2014) Chronic ethanol feeding modulates inflammatory mediators, activation of nuclear factor-kappaB, and responsiveness to endotoxin in murine Kupffer cells and circulating leukocytes. Mediators Inflamm 2014:808695. doi:10.1155/2014/808695 (PubMed PMID: 24623963; PubMed Central PMCID: PMC3928853)

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kawaratani H, Tsujimoto T, Douhara A, Takaya H, Moriya K, Namisaki T et al (2013) The effect of inflammatory cytokines in alcoholic liver disease. Mediators Inflamm 2013:495156. doi:10.1155/2013/495156 (PubMed PMID: 24385684; PubMed Central PMCID: PMC3872233)

    Article  PubMed  PubMed Central  Google Scholar 

  36. Huang J, Schriefer AE, Yang W, Cliften PF, Rudnick DA (2014) Identification of an epigenetic signature of early mouse liver regeneration that is disrupted by Zn-HDAC inhibition. Epigenetics 9(11):1521–1531. doi:10.4161/15592294.2014.983371

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lee YH, Seo D, Choi KJ, Andersen JB, Won MA, Kitade M et al (2014) Antitumor effects in hepatocarcinoma of isoform-selective inhibition of HDAC2. Cancer Res 74(17):4752–4761. doi:10.1158/0008-5472.CAN-13-3531 (PubMed PMID: 24958469; PubMed Central PMCID: PMC4155016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Niebergall LJ, Jacobs RL, Chaba T, Vance DE (2011) Phosphatidylcholine protects against steatosis in mice but not non-alcoholic steatohepatitis. Biochim Biophys Acta 1811(12):1177–1185. doi:10.1016/j.bbalip.2011.06.021

    Article  CAS  PubMed  Google Scholar 

  39. Tandy S, Chung RW, Kamili A, Wat E, Weir JM, Meikle PJ et al (2010) Hydrogenated phosphatidylcholine supplementation reduces hepatic lipid levels in mice fed a high-fat diet. Atherosclerosis 213(1):142–147. doi:10.1016/j.atherosclerosis.2010.07.050

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetric and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China

    Qunying Liu & Xietong Wang

  2. Department of Obstetrics, Eighth People’s Hospital of Qingdao, Qingdao, 266100, Shandong, China

    Qunying Liu, Yan Wang & Jun Han

  3. Department of Gastroenterology, Qingdao Hiser Medical Group, Qingdao, 266033, Shandong, China

    Fengyu Gao

  4. Department of Internal Medicine, Qingdao Women and Children Hospital, Qingdao, 266000, Shandong, China

    Xiangrong Liu

  5. Department of Obstetric and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China

    Jing Li

Authors
  1. Qunying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fengyu Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiangrong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xietong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xietong Wang.

Ethics declarations

Funding

There is no funding source for this study.

Conflict of interest

All authors declare that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Q., Gao, F., Liu, X. et al. Prenatal alcohol exposure and offspring liver dysfunction: a systematic review and meta-analysis. Arch Gynecol Obstet 294, 225–231 (2016). https://doi.org/10.1007/s00404-016-4109-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-016-4109-7

Keywords

Search

Navigation