Gestational diabetes modifies the association between PlGF in early pregnancy and preeclampsia in women with obesity.
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ABSTRACT: Objective
To identify clinical and biomarker risk factors for preeclampsia in women with obesity and to explore interactions with gestational diabetes, a condition associated with preeclampsia.Study design
In women with obesity (body mass index ≥ 30 kg/m2) from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we examined 8 clinical factors (socio-demographic characteristics, BMI, waist circumference and clinical variables) and 7 biomarkers (HDL cholesterol, hemoglobin A1c, adiponectin, interleukin-6, high sensitivity C-reactive protein, and placental growth factor (PlGF)) in the early second trimester for association with later development of preeclampsia using logistic regression. Factors were selected based on prior association with preeclampsia. Interaction with gestational diabetes was assessed.Main outcome measure
Preeclampsia.Results
Prevalence of preeclampsia was 7.3% (59/824). Factors independently associated with preeclampsia were higher mean arterial blood pressure (Odds Ratio (OR) 2.22; 95% Confidence Interval (CI) 1.58-3.12, per 10 mmHg) and lower PlGF (OR 1.39; 95% CI 1.03-1.87, per each lower 1 log2). The association of PlGF with preeclampsia was present amongst obese women without gestational diabetes (OR 1.91; 95% CI 1.32-2.78), but not in those with GDM (OR 1.05; 95% CI 0.67-1.63), p = 0.04 for interaction.Conclusion
The relationship between PlGF and preeclampsia differed in women with obesity according to gestational diabetes status, which may suggest different mechanistic pathways to preeclampsia. Whilst replication is required in other populations, this study suggests that performance of prediction models for preeclampsia should be confirmed in pre-specified subgroups.
SUBMITTER: Vieira MC
PROVIDER: S-EPMC6130745 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo analyze the interactions between maternal gestational diabetes mellitus (GDM) and genetically determined maternal body mass index (BMI) during pregnancy on offspring childhood obesity.Research design and methodsA total of 1114 Chinese mother-child pairs (560 GDM and 554 non-GDM) were included between August 2009 and July 2011. Maternal genetic risk score (GRS) of BMI during pregnancy was derived on the basis of 12 single nucleotide polymorphisms identified from a genome-wide association study. Offspring's BMI, BMI-for-age z score, weight, weight-for-age z score, waist circumference, sum of skinfolds, and body fat percentage during childhood were measured or calculated.ResultsMaternal GRS of BMI during pregnancy significantly interacted with maternal GDM status on childhood risks of overweight and obesity (all P for interaction <.05). After multivariable adjustment, per unit of GRS was associated with a 24% (P<.001) and a 28% (P<.001) increased risk of overweight and obesity among children of GDM mothers, whereas no significant associations were observed among children of mothers without GDM. In addition, per unit GRS of BMI during pregnancy was significantly associated with 0.16 kg/m2 higher BMI (P=.002), 0.09 higher BMI-for-age z score (P=.002), 0.24 kg higher weight (P=.04), 0.06 higher weight-for-age z score (P=.02), 0.28 cm higher waist circumference (P=.03), 0.94 mm higher sum of skinfolds (P=.004), and 0.37% higher body fat percentage (P=.03) among children of GDM mothers. There were no significant associations between maternal GRS of BMI during pregnancy and offspring's obesity-related outcomes among children of mothers without GDM.ConclusionOur findings for the first time indicate that maternal GDM status may modify the relation between genetically determined maternal BMI during pregnancy and offspring's obesity risk during childhood.
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Project description:AimsTo evaluate the clinical utility of first and second trimester prenatal screening biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM) risk in nulliparous women.MethodsWe conducted a population-based cohort study of nulliparous women participating in the California Prenatal Screening Program from 2009 to 2011 (n = 105,379). GDM was ascertained from hospital discharge records or birth certificates. Models including maternal characteristics and prenatal screening biomarkers were developed and validated. Risk stratification and reclassification were performed to assess clinical utility of the biomarkers.ResultsDecreased levels of first trimester pregnancy-associated plasma protein A (PAPP-A) and increased levels of second trimester unconjugated estriol (uE3) and dimeric inhibin A (INH) were associated with GDM. The addition of PAPP-A only and PAPP-A, uE3, and INH to maternal characteristics resulted in small, yet significant, increases in area under the receiver operating characteristic curve (AUC) (maternal characteristics only: AUC 0.714 (95% CI 0.703-0.724), maternal characteristics + PAPP-A: AUC 0.718 (95% CI 0.707-0.728), maternal characteristics + PAPP-A, uE3, and INH: AUC 0.722 (0.712-0.733)); however, no net improvement in classification was observed.ConclusionsPAPP-A, uE3, and INH have limited clinical utility for prediction of GDM risk in nulliparous women. Utility of other readily accessible clinical biomarkers in predicting GDM risk warrants further investigation.
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Project description:In the face of the obesity epidemic around the world, attention should be focused on the role of maternal obesity in the development of pregnancy. The purpose of this analysis was to evaluate the prediction of preeclampsia (PE) and isolated gestational hypertension (GH) for a number of maternal factors, in order to investigate the importance of pre-pregnancy obesity (body mass index, BMI ≥ 30 kg/m2), compared to other risk factors (e.g., prior PE, pregnancy weight gain (GWG), infertility treatment, interpregnancy interval, family history, the lack of vitamin supplementation, urogenital infection, and socioeconomic factors). In total, 912 women without chronic diseases were examined in a Polish prospective cohort of women with a single pregnancy (recruited in 2015-2016). Separate analyses were performed for the women who developed GH (n = 113) vs. 775 women who remained normotensive, as well as for those who developed PE (n = 24) vs. 775 controls. The probability of each disease was assessed for the base prediction model (age + primiparity) and for the model extended by one (test) variable, using logistic regression. Three measures were used to assess the prediction: area under curve (AUC) of the base and extended model, integrated discrimination improvement (IDI) (the index shows the difference between the value of the mean change in the predicted probability between the group of sick and healthy women when a new factor is added to the model), and net reclassification improvement (NRI) (the index 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 results for healthy and sick women). In the GH prediction, AUC increased most strongly when we added BMI (kg/m2) as a continuous variable (AUC = 0.716, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.068, p < 0.001). The addition of BMI as a continuous variable or BMI ≥ 25 kg/m2 improved the classification for healthy and sick women the most (NRI = 0.571, p < 0.001). In the PE prediction, AUC increased most strongly when we added BMI categories (AUC = 0.726, p < 0.001) to the base model. The highest IDI index was obtained for prior GH/PE (IDI = 0.050, p = 0.080). The addition of BMI categories improved the classification for healthy and sick women the most (NRI = 0.688; p = 0.001). After summing up the results of three indexes, the probability of hypertension in pregnancy was most strongly improved by BMI, including BMI ≥ 25 kg/m2 for the GH prediction, and BMI ≥ 30 kg/m2 for the PE prediction. Main conclusions: Pre-pregnancy BMI was the most likely factor to increase the probability of developing hypertension in pregnancy, compared to other risk factors. Hierarchies of PE and GH risk factors may suggest different (or common) mechanisms of their development.
| S-EPMC7551880 | biostudies-literature
Project description:Introduction:Pre-pregnancy obesity, gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are associated with each other. This is the first study to investigate whether genetic variants were associated with having GDM, and whether genetic variants-related GDM were associated with adiposity including pre-pregnancy obesity and excessive GWG in Turkish women. Patients and methods:Women with GDM (n?=?160) and without GDM (n?=?145) were included in case-controlled study. Genotyping of the HNF1A gene (p.I27L rs1169288, p.98V rs1800574, p.S487N rs2464196), the VDR gene (p.BsmI rs1544410, p.ApaI rs7975232, p.TaqI rs731236, p.FokI rs2228570), and FTO gene (rs9939609) SNPs were performed by using RT-PCR. Results:The FTO AA genotype was associated with an increased risk of having GDM (AA vs. AT?+?TT, 24.4% vs. 12.4%, OR?=?2.27, 95% CI [1.23-4.19], p?=?0.007). The HNF1A p.I27L GT/TT genotype was associated with increased GDM risk (GT?+?TT vs. GG-wild, 79.4% vs. 65.5%, OR?=?2.02, 95% CI 1.21-3.38], p?=?0.007). However, all VDR gene SNPs and the HNF1A p.A98V, p.S487N were not associated with having GDM (p?>?0.05). The FTO AA genotype was associated with an increased risk for pre-pregnancy overweight/obesity (OR?=?1.43, 95% CI [1.25-3.4], p?=?0.035), but not associated with excessive GWG after adjusting for pre-pregnancy weight (p?>?0.05). Pre-pregnancy weight, weight at delivery, and GWG did not differ in both VDR and HNF1A gene carriers (p?>?0.05). HOMA-IR and HbA1c were increased in both p.I27L TT and FTO AA genotype carriers (p?<?0.05). Conclusion:The adiposity-related gene FTO is associated with GDM by the effect of FTO on pre-pregnancy obesity. The diabetes-related p.I27L gene is associated with GDM by increasing insulin resistance.
| S-EPMC6518700 | biostudies-literature
Project description:Excessive pre-pregnancy weight is a known risk factor of pregnancy complications. The purpose of this analysis was to assess the relationship between several categories of maternal weight and the risk of developing hypertension and diabetes in pregnancy, and the relationship of these complications with the results of the newborn. It was carried out in a common cohort of pregnant women and taking into account the influence of disturbing factors. Our analysis was conducted in a prospective cohort of 912 Polish pregnant women, recruited during 2015-2016. We evaluated the women who subsequently developed diabetes with dietary modification (GDM-1) (n = 125) and with insulin therapy (GDM-2) (n = 21), as well as the women who developed gestational hypertension (GH) (n = 113) and preeclampsia (PE) (n = 24), compared to the healthy controls. Odds ratios of the complications (and confidence intervals (95%)) were calculated in the multivariate logistic regression. In the cohort, 10.8% of the women had pre-pregnancy obesity (body mass index (BMI) ? 30 kg/m2), and 36.8% had gestational weight gain (GWG) above the range of the Institute of Medicine recommendation. After correction for excessive GWG and other confounders, pre-pregnancy obesity (vs. normal BMI) was associated with a higher odds ratio of GH (AOR = 4.94; p < 0.001), PE (AOR = 8.61; p < 0.001), GDM-1 (AOR = 2.99; p < 0.001), and GDM-2 (AOR = 11.88; p <0.001). The threshold risk of development of GDM-2 occurred at lower BMI values (26.9 kg/m2), compared to GDM-1 (29.1 kg/m2). The threshold point for GH was 24.3 kg/m2, and for PE 23.1 kg/m2. For GWG above the range (vs. GWG in the range), the adjusted odds ratios of GH, PE, GDM-1, and GDM-2 were AOR = 1.71 (p = 0.045), AOR = 1.14 (p = 0.803), AOR = 0.74 (p = 0.245), and AOR = 0.76 (p = 0.672), respectively. The effect of maternal edema on all the results was negligible. In our cohort, hypertension and diabetes were associated with incorrect birth weight and gestational age at delivery. Conclusions: This study highlights the importance and influence of excessive pre-pregnancy maternal weight on the risk of pregnancy complications such as diabetes and hypertension which can impact fetal outcomes.
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