Fetal macrosomia in a Hispanic/Latinx predominant cohort and altered expressions of genes related to placental lipid transport and metabolism

Yang, Haiyan; He, Bin; Yallampalli, Chandra; Gao, Haijun

doi:10.1038/s41366-020-0610-y

Cited by 14 publications

(8 citation statements)

References 56 publications

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“…Among others, intensified placental transport of glucose and amino acids to the fetus and its higher mass were found in women and animals using a diet that favors obesity [ 45 , 49 , 50 , 51 ]. Changed transport of lipids in the placenta was found in obese women with GDM which can contribute to fetus overgrowth [ 52 ]. In the literature, the need for effective control of glycaemia is also emphasized during pregnancy in women without GDM, as a factor which is connected with macrosomia risk [ 7 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Maternal Weight in the Hierarchy of Macrosomia Predictors; Overall Effect of Analysis of Three Prediction Indicators

Lewandowska

2021

Nutrients

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So far it has not been established which maternal features play the most important role in newborn macrosomia. The aim of this study is to provide assessment of a hierarchy of twenty six (26) maternal characteristics in macrosomia prediction. A Polish prospective cohort of women with singleton pregnancy (N = 912) which was recruited in the years 2015−2016 has been studied. Two analyses were performed: for probability of macrosomia >4000 g (n = 97) (vs. 755 newborns 2500−4000 g); and for birthweight >90th percentile (n = 99) (vs. 741 newborns 10−90th percentile). A multiple logistic regression was used (with 95% confidence intervals (CI)). A hierarchy of significance of potential predictors was established after summing up of three prediction indicators (NRI, IDI and AUC) calculated for the basic prediction model (maternal age + parity) extended with one (test) predictor. ‘Net reclassification improvement’ (NRI) focuses on the reclassification table describing the number of women in whom an upward or downward shift in the disease probability value occurred after a new factor had been added, including the results for healthy and ill women. ‘Integrated discrimination improvement’ (IDI) shows the difference between the value of mean change in predicted probability between the group of ill and healthy women when a new factor is added to the model. The area under curve (AUC) is a commonly used indicator. Results. The macrosomia risk was the highest for prior macrosomia (AOR = 7.53, 95%CI: 3.15−18.00), p < 0.001). A few maternal characteristics were associated with more than three times higher macrosomia odds ratios, e.g., maternal obesity and gestational age ≥38 weeks. A different hierarchy was shown by the prediction study. Compared to the basic prediction model (AUC = 0.564 (0.501−0.627), p = 0.04), AUC increased most when pre-pregnancy weight (kg) was added to the base model (AUC = 0.706 (0.649−0.764), p < 0.001). The values of IDI and NRI were also the highest for the model with maternal weight (IDI = 0.061 (0.039−0.083), p < 0.001), and NRI = 0.538 (0.33−0.746), p < 0.001). Adding another factor to the base model was connected with significantly weaker prediction, e.g., for gestational age ≥ 38 weeks (AUC = 0.602 (0.543−0.662), p = 0.001), IDI = 0.009 (0.004; 0.013), p<0.001), and NRI = 0.155 (0.073; 0.237), p<0.001). After summing up the effects of NRI, IDI and AUC, the probability of macrosomia was most strongly improved (in order) by: pre-pregnancy weight, body mass index (BMI), excessive gestational weight gain (GWG) and BMI ≥ 25 kg/m2. Maternal height, prior macrosomia, fetal sex-son, and gestational diabetes mellitus (GDM) occupied an intermediate place in the hierarchy. The main conclusions: newer prediction indicators showed that (among 26 features) excessive pre-pregnancy weight/BMI and excessive GWG played a much more important role in macrosomia prediction than other maternal characteristics. These indicators more strongly highlighted the differences between predictors than the results of commonly used odds ratios.

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Section: Discussionmentioning

confidence: 99%

The Role of Maternal Weight in the Hierarchy of Macrosomia Predictors; Overall Effect of Analysis of Three Prediction Indicators

Lewandowska

2021

Nutrients

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“…The lipid-transport related genes are selectively activated in macrosomia placenta, and the lipid transport function may be enhanced, which suggests that altered placental lipid transport may contribute to fetal overgrowth in healthy women without GDM. It has been reported that the expression of these genes is also increased in the placenta of GDM women (28) and the changes of placental lipid transport may be related to fetal overgrowth in obese women with GDM [29]. And a previous study found that the expression of FATP6 and FAT/CD36 is increased in placental microvillous plasma membrane of individuals with intrauterine growth restriction (IUGR) [30].…”

Section: Discussionmentioning

confidence: 99%

Relationships Between Placental Lipid Transporters and Macrosomia in Healthy Pregnancy

Han¹,

Wang²,

Yan³

et al. 2021

Preprint

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Background: Macrosomia is a serious public health problem worldwide, the underlying etiology and mechanism of macrosomia born to healthy mothers are still unclear. Abnormal lipid transport during pregnancy exerts potential and adverse impacts on fetus, our study aimed to assess associations between macrosomia and placental expression levels of lipid transport-related genes and umbilical cord blood lipid concentrations in healthy pregnancy.Methods: We conducted a case-control study of 38 macrosomia and 39 normal-birth-weight newborns in healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Results: The single factor analysis showed that placental mRNA and protein expression levels of PPARα, PPARγ, FABPpm, LXRα, FABP3, FABP4 and FAT/CD36 were significantly higher and cord blood total cholesterol, low-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) concentrations were significantly lower in macrosomia group. Further analysis found that placental PPARγ, FABP4 and FABP3 mRNA expression levels were positively correlated with high-density lipoprotein cholesterol, NEFA and triglycerides concentrations in macrosomia cord blood, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (AOR=3.022; 95%CI:1.032-8.853) and FAT/CD36 (AOR=2.989; 95%CI:1.029-8.679) expression increased the risk of delivering macrosomia. Conclusions: The increase of PPARα and FAT/CD36 mRNA expression levels is associated with the occurrence of macrosomia, suggesting that they may be important regulators during placental lipid transport in macrosomia.

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“…It undoubtedly exacerbated the fetal overgrowth, thereby linking the formation of macrosomia and LGA. Second, the increase of placental lipid metabolism may act a regulatory role in the fat accumulation of the fetus in turn forming macrosomia (50,51). Third, epigenetic regulation occurs via numbers of procedures including DNA methylation (DNAm) and so on.…”

Section: Adverse Infant Birth Weightmentioning

confidence: 99%

Impact of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus: A systematic review and meta-analysis

Zhu

Pan²,

Jiang³

et al. 2022

Preprint

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Background Pre-pregnancy BMI and gestational weight gain are associated with pregnancy outcomes. This review aimed to explore pregestational BMI and gestational weight gain and their association with pregnancy complications in Chinese women with gestational diabetes mellitus. Moreover, the prevalence of inappropriate weight gain during pregnancy among them was estimated. Methods Nine databases including PubMed, Web of Science, Cochrane Library, Embase, Scopus, CNKI, Wangfang, VIP, and China Biology Medicine disc were searched from inception to March 2022. Outcomes evaluated were macrosomia, large for gestational age (LGA), small for gestational age (SGA), low birth weight (LBW), preterm birth, cesarean section (CS), and gestational hypertension (GH). Two researchers independently assessed the eligibility and quality of included studies and extracted data. Fixed and random effect models were used to pool the results. I2 index was used to assess the statistical heterogeneity. All analyses were performed using Stata software. Results 13,831 potential studies were identified, and 19 studies remain after removing duplicate and unrelated articles. Pregestational obesity and excess gestational weight gain are association with a higher risk of macrosomia (OR=2.83[2.13 to 3.77]; OR=2.13[1.92 to 2.38]), LGA (OR=3.38[2.71 to 4.23]; OR=2.15[1.82 to 2.53]), CS (OR=2.46[2.04 to 2.98]; OR=1.38[1.41 to 1.66]), and GH (OR=4.42[1.72 to 11.34]; OR=2.20[1.71 to 2.82]). Pregestational underweight and insufficient gestational weight gain are related to a higher risk of SGA (OR=1.90[1.63 to 2.22]; OR=1.34[1.22 to 1.48]) and LBW (OR=2.48[1.41 to 4.36]; OR=1.89[1.38 to 2.60]). As to preterm birth, the conclusion remains unclear. The prevalence of excess and below the weight gain recommendations of the Institute of Medicine is up to 35.5% and 27.3%. Gestational diabetes may have a potential synergistic effect with inappropriate weight changes, which needs to be further explored. Conclusion Weight management before and during pregnancy is crucial for all women including Chinese women with gestational diabetes.

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Fetal macrosomia in a Hispanic/Latinx predominant cohort and altered expressions of genes related to placental lipid transport and metabolism

Cited by 14 publications

References 56 publications

The Role of Maternal Weight in the Hierarchy of Macrosomia Predictors; Overall Effect of Analysis of Three Prediction Indicators

The Role of Maternal Weight in the Hierarchy of Macrosomia Predictors; Overall Effect of Analysis of Three Prediction Indicators

Relationships Between Placental Lipid Transporters and Macrosomia in Healthy Pregnancy

Impact of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus: A systematic review and meta-analysis

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