First trimester prenatal screening biomarkers and gestational diabetes mellitus: A systematic review and meta-analysis

Donovan, Brittney M.; Nidey, Nichole; Jasper, Elizabeth A.; Robinson, Jennifer G.; Bao, Wei; Saftlas, Audrey F.; Ryckman, Kelli K.

doi:10.1371/journal.pone.0201319

Cited by 42 publications

(29 citation statements)

References 42 publications

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“…Even a PAPP-A value <1 MoM was predictive of GDM, whereas a β-hCG value >2 MoM was inversely associated with GDM. Our findings are consistent with a couple of previous studies [11,16], other than a recent systematic review and meta-analysis [30], indicating that both reduced first trimester levels of PAPP-A and free β-hCG are associated with the risk of GDM development. In addition, our data are consistent with those reported in a large Thailandian population, indicating a specific protective effect against GDM of a β-hCG value >2 MoM [18].…”

Section: Discussionsupporting

confidence: 93%

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus

Visconti

Quaresima

Chiefari

et al. 2019

IJERPH

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Background—The first trimester combined test (FTCT) is an effective screening tool to estimate the risk of fetal aneuploidy. It is obtained by the combination of maternal age, ultrasound fetal nuchal translucency (NT) measurement, and the maternal serum markers free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein A (PAPP-A). However, conflicting data have been reported about the association of FTCT, β-hCG, or PAPP-A with the subsequent diagnosis of gestational diabetes mellitus (GDM). Research design and methods—2410 consecutive singleton pregnant women were retrospectively enrolled in Calabria, Southern Italy. All participants underwent examinations for FTCT at 11–13 weeks (plus 6 days) of gestation, and screening for GDM at 16–18 and/or 24–28 weeks of gestation, in accordance with current Italian guidelines and the International Association Diabetes Pregnancy Study Groups (IADPSG) glycemic cut-offs. Data were examined by univariate and logistic regression analyses. Results—1814 (75.3%) pregnant women were normal glucose tolerant, while 596 (24.7%) were diagnosed with GDM. Spearman univariate analysis demonstrated a correlation between FTCT values and subsequent GDM diagnosis (ρ = 0.048, p = 0.018). The logistic regression analysis showed that women with a FTCT <1:10000 had a major GDM risk (p = 0.016), similar to women with a PAPP-A <1 multiple of the expected normal median (MoM, p = 0.014). Conversely, women with β-hCG ≥2.0 MoM had a reduced risk of GDM (p = 0.014). Conclusions—Our findings indicate that GDM susceptibility increases with fetal aneuploidy risk, and that FTCT and its related maternal serum parameters can be used as early predictors of GDM.

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Section: Discussionsupporting

confidence: 93%

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus

Visconti

Quaresima

Chiefari

et al. 2019

IJERPH

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“…The relationship with metabolism has been studied especially for Gestational Diabetes Mellitus (GDM). Several studies found that, in the first trimester of pregnancy, the values of PAPP-A levels were lower in patients who developed GDM, compared to patients with normoglycemic pregnant, suggesting a possible role of this biochemical marker in GDM screening in early pregnancy 34,35 . From these data it can be deduced that low PAPP-A concentrations could be an indicator of a pathophysiological process that will lead to GDM and type 2 DM years after pregnancy, but which is already in place months before the disease becomes striking.…”

Section: Discussionmentioning

confidence: 99%

First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring

Fruscalzo

Cividino

Rossetti

et al. 2020

Sci Rep

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Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) are known to be associated with the development of pregnancy-related complications like small for gestational age infants, intrauterine fetal demise, gestational diabetes and preeclampsia. The study aims to find possible long-term correlations with the development of metabolic and cardiovascular complications in the mothers and their progeny in later life. This is a retrospective cohort study conducted on consecutive unselected women screened for chromosomal anomalies in the first trimester of pregnancy between 2004 and 2010. PAPP-A values as well as clinical data collected at childbirth were considered. A maternal and neonatal follow-up was performed through a telephone interview with the mother during 2015. The body-mass-index and the presence of cardiovascular diseases, dyslipidaemia and diabetes mellitus were evaluated. The analysis included 988 patients. The median time of follow-up was 7 years (IQR 6-9). Lower first trimester maternal blood PAPP-A quartiles were associated with small stature of the offspring (z-score 1st-2nd quartile 0.37 IQR −0.42 and 1.17 vs 3rd-4th quartile 0.67 IQR −0.17 and 1.36, p < 0.05). Furthermore, low first trimester PAPP-A in pregnancy without other gestations following the index one, in Kaplan-Meier analysis was associated to a significant increase of hypoglycemic agents use at 7 and 10 years (respectively 1.12% CI.95 0-2.38% and 5.45% CI.95 0-10.82%) compared to the control group of high first trimester PAPP-A values (0% CI.95 0-0%) (p < 0.05). Low PAPP-A serum levels in the first trimester of pregnancy are associated with short stature in offspring and de-novo development of maternal diabetes mellitus in later life.

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“…A systematic review and meta-analysis by Donovan et al [ 286 ] included 13 studies and 83,921 subjects (GDM n = 3786). While the study identified a high degree of heterogeneity mostly due to the analysis method, the GDM diagnostic criteria and the ethnicity of subjects involved, the overall analysis and sub-analysis identified significantly lower first-trimester PAPP-A levels in women who developed GDM compared with controls with even lower levels in GDM women diagnosed prior to 24 weeks of gestation.…”

Section: Cytokinesmentioning

confidence: 99%

Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes—A Scoping Review

Bogdanet

Reddin

Murphy

et al. 2021

JCM

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Introduction: Gestational diabetes (GDM), defined as hyperglycemia with onset or initial recognition during pregnancy, has a rising prevalence paralleling the rise in type 2 diabetes (T2DM) and obesity. GDM is associated with short-term and long-term consequences for both mother and child. Therefore, it is crucial we efficiently identify all cases and initiate early treatment, reducing fetal exposure to hyperglycemia and reducing GDM-related adverse pregnancy outcomes. For this reason, GDM screening is recommended as part of routine pregnancy care. The current screening method, the oral glucose tolerance test (OGTT), is a lengthy, cumbersome and inconvenient test with poor reproducibility. Newer biomarkers that do not necessitate a fasting sample are needed for the prompt diagnosis of GDM. The aim of this scoping review is to highlight and describe emerging protein biomarkers that fulfill these requirements for the diagnosis of GDM. Materials and Methods: This scoping review was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for scoping reviews using Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing & Allied Health Literature (CINAHL), PubMed, Embase and Web of Science with a double screening and extraction process. The search included all articles published in the literature to July 2020. Results: Of the 3519 original database citations identified, 385 were eligible for full-text review. Of these, 332 (86.2%) were included in the scoping review providing a total of 589 biomarkers studied in relation to GDM diagnosis. Given the high number of biomarkers identified, three post hoc criteria were introduced to reduce the items set for discussion: we chose only protein biomarkers with at least five citations in the articles identified by our search and published in the years 2017–2020. When applied, these criteria identified a total of 15 biomarkers, which went forward for review and discussion. Conclusions: This review details protein biomarkers that have been studied to find a suitable test for GDM diagnosis with the potential to replace the OGTT used in current GDM screening protocols. Ongoing research efforts will continue to identify more accurate and practical biomarkers to take GDM screening and diagnosis into the 21st century.

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First trimester prenatal screening biomarkers and gestational diabetes mellitus: A systematic review and meta-analysis

Cited by 42 publications

References 42 publications

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus

First Trimester Combined Test (FTCT) as a Predictor of Gestational Diabetes Mellitus

First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring

Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes—A Scoping Review

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