Continuous association of total bile acid levels with the risk of small for gestational age infants

Li, Li; Chen, Wei; Ma, Li; Liu, Zhi Bing; Xue, Lingxiao; Gao, Xing; Liu, Yan; Wang, Hua; Zhao, Mingqiu; Li, Xiao Lan; Liu, Cong; Xu, De Xiang; Chen, Yuan Hua

doi:10.1038/s41598-020-66138-y

Cited by 16 publications

(21 citation statements)

References 52 publications

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“… 16 A recent study also reported that birth weight decreased with increasing sTBA levels in a cohort of 13 801 pregnant individuals in China. 15 In this study, we observed a J-shaped nonlinear association between sTBA and birth weight and a negative association between sTBA concentrations of 4.08 μg/mL or greater and birth weight in a larger cohort (ie, with 68 245 pregnant individuals). The inconsistencies among these studies may partially be explained by differences in sample sizes, population ethnicity, and the diagnostic criteria for ICP or gestational hypercholanemia.…”

Section: Discussionmentioning

confidence: 47%

Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Song

Chen²,

Chen

et al. 2021

JAMA Netw Open

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IMPORTANCE Bile acids play essential roles in metabolic modulation. Excessive serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes; however, their association with the risk of intrauterine growth restriction (IUGR) remains unclear. OBJECTIVE To investigate the association between maternal sTBA concentration during pregnancy and the risk of IUGR. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included pregnant individuals who delivered live singleton neonates and had regular antenatal examination records available at a hospital-based center in Shanghai, China, from 2014 to 2018. Data were analyzed from July to November 2020. EXPOSURES Maternal sTBA concentration during pregnancy. MAIN OUTCOMES AND MEASURES Fetal birth weight and probability of low birth weight (LBW) and IUGR. RESULTSThis study included 68 245 singleton pregnancies with live births for analysis. The mean (SD) age of the pregnant individuals was 30.5 (3.8) years, 67 168 patients (98.4%) were Han, and 50 155 (73.5%) were nulliparous. Nonlinear regression models suggested that there was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight, with a steep decrease in birth weight at high sTBA levels (estimated mean [SE] birth weight for sTBA of 40.8 ug/mL, 2879 [39.9] g) and greater birth weights at lower sTBA levels (estimated mean [SE] birth weight for sTBA 0.4 μg/mL, 3290 [3.9] g; and for 4.1 μg/mL, 3334 [1.6] g). Lower birth weight and a higher incidence of IUGR were observed in patients with gestational hypercholanemia (sTBA Ն4.08 μg/mL) compared with those without gestational hypercholanemia (birth weight: estimated adjusted mean [SE], 3309 [3.32] vs 3338 [0.80] g; P = .005; incidence of IUGR: 62 of 4467 [1.4%] vs 312 of 63 778 [0.5%]; P < .001). Moreover, compared with patients with sTBA concentrations of less than 4.08 μg/mL, those with gestational hypercholanemia had an increased risk of LBW (adjusted odds ratio [aOR], 1.29; 95% CI, 1.09-1.53) and IUGR (aOR, 2.18; 95% CI, 1.62-2.91). In addition, there was an additive interaction between hypertensive disorders in pregnancy (HDP) and hypercholanemia on LBW and IUGR risk. The highest risks of LBW and IUGR were found in pregnant individuals with both HDP and hypercholanemia compared with those with normotensive pregnancies with sTBA concentrations less than 4.

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Section: Discussionmentioning

confidence: 47%

Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Song

Chen²,

Chen

et al. 2021

JAMA Netw Open

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“…Serum TBA levels were measured by an automatic biochemical analyzer (Dirui CS-T300, Ltd, Changchun, China) according to our previous protocol 44 .…”

Section: Methodsmentioning

confidence: 99%

Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population

Gao

Liu

et al. 2020

Sci Rep

Self Cite

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Studies on the risk factors for intrahepatic cholestasis of pregnancy (ICP) in a population-based cohort are lacking. We assess the prevalence and risk factors of ICP in a Chinese population. In this study, a cohort study was conducted that included 12,200 eligible pregnant women. The overall incidence of ICP in this cohort was 6.06%. With increasing maternal age, the incidence of ICP decreased in women younger than 30 years of age but increased in those older than 30. With increasing pre-pregnancy BMI, the incidence of ICP decreased if the pre-pregnancy BMI was less than 23 kg/m2 but increased if it was 23 kg/m2 or higher. Further analysis showed that the risk of ICP increased when maternal age was < 25 years (Adjusted RR 2.01; 95% CI 1.64–2.47) or ≥ 35 years (Adjusted RR 1.34; 95% CI 1.02–1.76). Furthermore, an increased risk of ICP was associated with pre-pregnancy underweight (adjusted RR 1.27; 95% CI 1.04–1.56), inadequate gestational weight gain (GWG) (adjusted RR 1.58; 95% CI 1.28–1.96), lower maternal education (adjusted RR 2.96; 95% CI 2.35–3.74), multiparity (adjusted RR 1.54; 95% CI 1.23–1.93), and twin/multiple pregnancies (adjusted RR 2.12; 95% CI 1.25–3.58). Maternal age (< 25 or ≥ 35 years), underweight, inadequate GWG, lower maternal education, multiparity, and twin/multiple pregnancies were identified as risk factors of ICP.

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“…ICP has been associated with adverse fetal outcomes, including spontaneous preterm birth, respiratory distress, low Apgar scores, fetal distress and fetal death [3][4][5][6][7]. For example, Li Li et al reported that birth size was reduced, whereas the rate of small-for-gestational-age infants was increased across increasing categories of serum total TBA [8]. It has been noted that approximately 2-4% of ICP pregnancies are affected by fetal mortality [9,10].…”

Section: Introductionmentioning

confidence: 99%

Whole-exome sequencing identifies novel mutations in ABC transporter genes associated with intrahepatic cholestasis of pregnancy disease: a case-control study

Liu

Lai

Xin

et al. 2021

BMC Pregnancy Childbirth

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Background Intrahepatic cholestasis of pregnancy (ICP) can cause premature delivery and stillbirth. Previous studies have reported that mutations in ABC transporter genes strongly influence the transport of bile salts. However, to date, their effects are still largely elusive. Methods A whole-exome sequencing (WES) approach was used to detect novel variants. Rare novel exonic variants (minor allele frequencies: MAF < 1%) were analyzed. Three web-available tools, namely, SIFT, Mutation Taster and FATHMM, were used to predict protein damage. Protein structure modeling and comparisons between reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively. Results We detected a total of 2953 mutations in 44 ABC family transporter genes. When the MAF of loci was controlled in all databases at less than 0.01, 320 mutations were reserved for further analysis. Among these mutations, 42 were novel. We classified these loci into four groups (the damaging, probably damaging, possibly damaging, and neutral groups) according to the prediction results, of which 7 novel possible pathogenic mutations were identified that were located in known functional genes, including ABCB4 (Trp708Ter, Gly527Glu and Lys386Glu), ABCB11 (Gln1194Ter, Gln605Pro and Leu589Met) and ABCC2 (Ser1342Tyr), in the damaging group. New mutations in the first two genes were reported in our recent article. In addition, compared to the wild-type protein structure, the ABCC2 Ser1342Tyr-modified protein structure showed a slight change in the chemical bond lengths of ATP ligand-binding amino acid side chains. In placental tissue, the expression level of the ABCC2 gene in patients with ICP was significantly higher (P < 0.05) than that in healthy pregnant women. In particular, the patients with two mutations in ABC family genes had higher average values of total bile acids (TBA), aspartate transaminase (AST), direct bilirubin (DBIL), total cholesterol (CHOL), triglycerides (TG) and high-density lipoprotein (HDL) than the patients who had one mutation, no mutation in ABC genes and local controls. Conclusions Our present study provide new insight into the genetic architecture of ICP and will benefit the final identification of the underlying mutations.

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Continuous association of total bile acid levels with the risk of small for gestational age infants

Cited by 16 publications

References 52 publications

Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population

Whole-exome sequencing identifies novel mutations in ABC transporter genes associated with intrahepatic cholestasis of pregnancy disease: a case-control study

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