From pregnant women to infants: Non-alcoholic fatty liver disease is a poor inheritance
2020; Elsevier BV; Volume: 73; Issue: 6 Linguagem: Inglês
10.1016/j.jhep.2020.06.043
ISSN1600-0641
AutoresAntonella Mosca, Nadia Panera, Giuseppe Maggiore, Anna Alisi,
Tópico(s)Pregnancy and preeclampsia studies
ResumoIn their otherwise excellent study, Sarkar et al.[1]Sarkar M. Grab J. Dodge J.L. Gunderson E.P. Rubin J. Irani R.A. et al.Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomes.J Hepatol. 2020; 73: 516-522Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar do not analyze the possibility of long-term hepatic effects in children born to mothers with non-alcoholic fatty liver disease (NAFLD). In our preliminary study, we retrospectively analyzed available data from pregnancy and at birth in 100 consecutive overweight/obese children (average age 9.8 years, BMI 27.3 kg/m2) observed in our pediatric center from January 2017 to September 2019, with a biopsy-proven diagnosis of NAFLD. Forty-five percent of children with NAFLD were born to mothers with ultrasound evidence of steatosis, while the remaining were not. As shown in Table 1, during pregnancy, 45% of mothers were obese, 23% had impaired glucose tolerance (IGT), 22% had hypertransaminasemia, and 51% had hypertension. Moreover, 27% of children with NAFLD were born preterm, 15% were small gestational age (SGA), and 5% large gestational age. When considering only mothers with steatosis, all were obese, 33.3% had IGT, 40% hypertransaminasemia, and 84.4% hypertension (Table 1).Table 1Characteristics of mothers in pregnancy and children at birth and at diagnosis of NAFLD.All(100)Maternal steatosis(45)No maternal steatosis(55)p steatosis vs. no maternal steatosisMother comorbidities in pregnancy Obesity (%)45 (45)45 (100)0– IGT (%)∗23 (23)15 (33.3)8 (14.5)0.05 Hypertransaminasemia (%)∗22 (22)18 (40)4 (7.3)0.03 Hypertension (%)∗51 (51)38 (84.4)13 (23.6)0.02Children characteristics at birth Male/Female45/5521/2424/21– Preterm, n (%)∗27 (27)18 (40)8 (14.5)0.04 Birth weight, g; median (IQR)3,050 (1,600–4,050)3,010 (1,200–3,960)3,140 (1,750–4,100)0.65 Gestational age in months; median (IQR)38 (32–41)38 (30–40)38 (34–41)0.91 SGA, n (%)∗15 (15)10 (22.2)5 (9)0.05 LGA, n (%)∗5 (5)3 (6.6)2 (3.6)0.91Children anthropometrics at diagnosis of NAFLD Age, years; mean ± (SD)9.6 (1.3)9.5 (1.2)9.9 (1.1)0.76 Weight, kg; mean ± (SD)67.9 (5.3)69.2 (11.3)67.6 (10.3)0.84 BMI, kg/m2; mean ± (SD)25.6 (4.1)27.2 (3.3)25.9 (3.9)0.45 WC, cm; mean ± (SD)82.9 (12.7)82.1 (11.4)81.9 (10.3)0.63 z-BMI; mean ± (SD)1.99 (0.4)1.98 (0.5)1.97 (0.4)0.79Children liver histology Steatosis2.1 (0.8)1.98 (0.8)1.99 (0.9)0.47 Lobular Inflammation∗∗0.8 (0.4)1.2 (0.8)0.7 (0.5)0.05 Portal Inflammation1 (0.4)1.1 (0.3)0.99 (0.4)0.09 Ballooning∗∗1.1 (0.7)1.4 (0.6)1.1 (0.5)0.04 Fibrosis∗∗1.02 (0.6)1.4 (0.6)0.9 (0.4)0.03IGT, impaired glucose tolerance; LGA, large gestational age; NAFLD, non-alcoholic fatty liver disease; SGA, small gestational age; WC, waist circumference.Normally distributed data are described as means ± SDs and non-normally distributed data are expressed as medians and IQRs. Difference between proportions were tested using the Chi-square test∗. Data were tested for differences by Student's t test∗∗. Differences statistically significant at p ≤0.05 are reported in bold. Open table in a new tab IGT, impaired glucose tolerance; LGA, large gestational age; NAFLD, non-alcoholic fatty liver disease; SGA, small gestational age; WC, waist circumference. Normally distributed data are described as means ± SDs and non-normally distributed data are expressed as medians and IQRs. Difference between proportions were tested using the Chi-square test∗. Data were tested for differences by Student's t test∗∗. Differences statistically significant at p ≤0.05 are reported in bold. At the time of diagnosis of NAFLD in children most mothers had unresolved obesity, except 3 after bariatric surgery, and more than 50% of mothers had type 2 diabetes (T2D) and high blood pressure. In our cohort, 46% of children showed a histological picture of non-alcoholic steatohepatitis (NASH), and this prevalence increases to 64.4% if we consider only the group of children with a mother with steatosis. Interestingly, the children born to mothers with steatosis exhibited a significantly higher degree of inflammation, ballooning and fibrosis than children from mothers without steatosis. Recent studies have shown that several prenatal factors are responsible for the pathogenesis of pediatric NAFLD, including maternal obesity, gestational diabetes, and metabolic syndrome (MetS) in pregnancy, as well as low birth weight. High maternal BMI has been shown to be a predictive factor of increased liver lipid content in infants, measured by magnetic resonance imaging in early childhood.[2]Gale C. Thomas E.L. Jeffries S. Durighel G. Logan K.M. Parkinson J.R. et al.Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study.Am J Clin Nutr. 2014; 99: 1034-1040Crossref PubMed Scopus (11) Google Scholar Moreover, it has been reported that children of women who were obese at the start of pregnancy were twice as likely to have NAFLD in adolescence.[3]Ayonrinde O.T. Oddy W.H. Adams L.A. Mori T.A. Beilin L.J. de Klerk N. et al.Infant nutrition and maternal obesity influence the risk of non-alcoholic fatty liver disease in adolescents.J Hepatol. 2017; 67: 568-576Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar An excess of maternal fatty acids could result in the accumulation of fetal ectopic fat, as the fetus is unable to expand fat deposits to buffer the release of transplacental lipids by the mother and thus could be a first mechanism of predisposition to obesity and insulin resistance underlying the multi-hit hypothesis of NAFLD onset in pediatrics.[4]Mann J.P. Valenti L. Scorletti E. Byrne C.D. Nobili V. Nonalcoholic fatty liver disease in children.Semin Liver Dis. 2018; 38: 1-13Crossref PubMed Scopus (58) Google Scholar Another prenatal factor, in accordance with the “thrifty phenotype” hypothesis, is that intrauterine growth retardation can lead to several postnatal metabolic problems such as obesity, NAFLD and MetS.[5]Hales C.N. Barker D.J. The thrifty phenotype hypothesis.Br Med Bull. 2001; 60: 5-20Crossref PubMed Scopus (1867) Google Scholar These conditions, as demonstrated by our research group, are also associated with many other factors, such as family socioeconomic status, genetics, breastfeeding and the family diet.[6]Mosca A. De Cosmi V. Parazzini F. Raponi M. Alisi A. Agostoni C. et al.The role of genetic predisposition, programing during fetal life, family conditions, and post-natal diet in the development of pediatric fatty liver disease.J Pediatr. 2019; 211: 72-77.e4Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Interestingly, our preliminary data suggest that children with pre-adolescent NAFLD born to mothers with liver steatosis are predisposed to perinatal complications, such as preterm birth and SGA. This data suggests that previous evidence of the association between pediatric NAFLD and intrauterine growth restriction could depend on maternal metabolic phenotype during pregnancy.[7]Bugianesi E. Bizzarri C. Rosso C. Mosca A. Panera N. Veraldi S. et al.Low birthweight increases the likelihood of severe steatosis in pediatric non-alcoholic fatty liver disease.Am J Gastroenterol. 2017; 112: 1277-1286Crossref PubMed Scopus (21) Google Scholar In summary, all these findings highlight that pre-natal and post-natal complications can endanger not only mothers but also newborns, and that children exposed in utero to a maternal steatosis niche are more likely to develop early obesity and NAFLD with more severe histologic liver damage. In conclusion, the study by Sarkar et al., opens a new question regarding the impact of maternal NAFLD on infant complications at birth. Long-term follow-up of their cohort could help establish if NAFLD in pregnant women may trigger the same disease in their offspring, as our preliminary data suggests. This research was funded by the Italian Ministry of Health (Fondi di Ricerca Corrente 2020) to Anna Alisi. AA designed and supervised the study, and drafted the manuscript. AM, NP acquired and analyzed data, and drafted the manuscript. GM authors critically revised the manuscript. All and approved the final version. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. We would like to thank Dr. Valerio Nobili for being a wonderful mentor who inspired this study and lives forever in our hearts. Download .pdf (.17 MB) Help with pdf files disclosures.pdf Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomesJournal of HepatologyVol. 73Issue 3PreviewThe prevalence of non-alcoholic fatty liver disease (NAFLD) is rising in young adults, with potential implications for reproductive-aged women. Whether NAFLD during pregnancy confers more serious risks for maternal or perinatal health is unclear. Full-Text PDF
Referência(s)