Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using ...different oral glucose tolerance test (OGTT) thresholds.
This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-h OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1 h ≥ 10.0 or 2-h glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1-5.2 mmol/L and/or 2-h glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-h glucose 7.8-8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Controls were normoglycaemic according to all criteria (fasting glucose < 5.1 mmol/L, 1-h glucose < 10.0 mmol/L and 2-h glucose < 8.5 mmol/L, n = 3031). Untreated mild hyperglycemia groups were compared to controls and treated GDM groups. The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality - was analysed using multivariate logistic regression.
The risk for the adverse neonatal outcome in untreated mild hyperglycemia was not increased compared to controls (adjusted odds ratio aOR: 1.01, 95% confidence interval CI: 0.71-1.44, using the IADPSG criteria; aOR: 1.05, 95% CI: 0.60-1.85, using the NICE criteria). The risk was lower compared to the treated IADPSG (aOR 0.38, 95% CI 0.27-0.53) or the treated NICE group (aOR 0.32, 95% CI 0.18-0.57).
The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia compared to normoglycaemic controls and was lower than in the treated GDM groups. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 h seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.
Abstract
Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case–control study including 1040 women ...with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides—Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)—were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression were used to analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among women with subsequent GDM than among controls. After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors of GDM, women in their highest quartile had 1.44-fold (95% CI 1.07–1.95), 2.17-fold (95% CI 1.57–3.00) and 1.63-fold (95% CI 1.19–2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM.
Abstract
Background
Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the ...association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring.
Methods
This Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status.
Results
The risk of major CAs was higher in the GDM-exposed (
n
= 336, 5.09%) than in the non-exposed group (
n
= 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05–1.33,
p
= 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30,
p
= 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69–3.66,
p
< 0.001). The aOR was 1.93 (95% Cl: 1.25–2.99,
p
= 0.003).
Conclusions
Offspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking.
Objective To study the roles of self-reported symptoms and/or prior diagnosis of polycystic ovary syndrome (PCOS) and other potential risk factors for gestational diabetes mellitus (GDM) and to ...clarify whether the screening of GDM in early pregnancy is beneficial for all women with PCOS. Design The FinnGeDi multicentre case-control study including 1146 women with singleton pregnancies diagnosed with GDM and 1066 non-diabetic pregnant women. There were 174 women with PCOS (symptoms and/or diagnosis self-reported by a questionnaire) and 1767 women without PCOS (data missing for 271). Methods The study population (N = 1941) was divided into four subgroups: GDM + PCOS (N = 105), GDM + non-PCOS (N = 909), non-GDM + PCOS (N = 69), and controls (N = 858). The participants’ characteristics and their parents’ medical histories were compared. Results The prevalence of PCOS was 10.4% among GDM women and 7.4% among non-diabetics (odds ratios (OR) 1.44, 95% CI: 1.05–1.97), but PCOS was not an independent risk for GDM after adjustments for participants’ age and pre-pregnancy BMI (OR 1.07, 95% CI: 0.74–1.54). In a multivariate logistic regression analysis, the most significant parameters associated with GDM were overweight, obesity, age ≥35 years, participant’s mother’s history of GDM, either parent’s history of type 2 diabetes (T2D) and participant’s own preterm birth. Conclusions The increased risk of GDM in women with PCOS was related to obesity and increased maternal age rather than to PCOS itself, suggesting that routine early screening of GDM in PCOS women without other risk factors should be reconsidered. Instead, family history of GDM/T2D and own preterm birth were independent risk factors for GDM.
Background:
Pre-pregnancy obesity, excess gestational weight gain (GWG), and gestational diabetes (GDM) increase fetal growth. Our aim was to assess whether normal GWG is associated with lower risk ...for a large-for-gestational-age (LGA; over the 90th percentile of birth weight for sex and gestational age) infant and lower birth weight standard deviation (SD) score in the presence of GDM and maternal obesity.
Methods:
This multicenter case-control study is part of the Finnish Gestational Diabetes (FinnGeDi) Study and includes singleton pregnancies of 1,055 women with GDM and 1,032 non-diabetic controls. Women were divided into 12 subgroups according to their GDM status, pre-pregnancy body mass index (BMI; kg/m
2
), and GWG. Non-diabetic women with normal BMI and normal GWG (according to Institute of Medicine recommendations) served as a reference group.
Results:
The prevalence of LGA birth was 12.2% among women with GDM and 6.2% among non-diabetic women (
p
< 0.001). Among all women, normal GWG was associated with lower odds of LGA odds ratio (OR) 0.57, 95% CI: 0.41–0.78. Among women with both obesity and GDM, the odds for giving birth to a LGA infant was 2.25-fold (95% CI: 1.04–4.85) among those with normal GWG and 7.63-fold (95% CI: 4.25–13.7) among those with excess GWG compared with the reference group. Compared with excess GWG, normal GWG was associated with 0.71 SD (95% CI: 0.47–0.97) lower birth weight SD score among women with GDM and obesity. Newborns of normal weight women with GDM and normal GWG had 0.28 SD (95% CI: 0.05–0.51) lower birth weight SD scores compared with their counterparts with excess GWG. In addition, in the group of normal weight non-diabetic women, normal GWG was associated with 0.46 SD (95% CI: 0.30–0.61) lower birth weight SD scores compared with excess GWG.
Conclusion:
GDM, obesity, and excess GWG are associated with higher risk for LGA infants. Interventions aiming at normal GWG have the potential to lower LGA rate and birth weight SD scores even when GDM and obesity are present.
Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be ...partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.
Gestational diabetes mellitus (GDM) is associated with an increased risk of obesity and insulin resistance in offspring later in life, which might be explained by epigenetic changes in response to ...maternal hyperglycemic exposure.
We explored the association between GDM exposure and maternal blood and newborn cord blood methylation in 536 mother-offspring pairs from the prospective FinnGeDi cohort using Illumina MethylationEPIC 850K BeadChip arrays. We assessed two hypotheses. First, we tested for shared maternal and offspring epigenetic effects resulting from GDM exposure. Second, we tested whether GDM exposure and maternal methylation had an epigenetic effect on the offspring.
We did not find any epigenetic marks (differentially methylated CpG probes) with shared and consistent effects between mothers and offspring. After including maternal methylation in the model, we identified a single significant (false discovery rate 1.38 × 10
) CpG at the cg22790973 probe (
associated with GDM. We identified seven additional FDR-significant interactions of maternal methylation and GDM status, with the strongest association at the same cg22790973 probe (
, as well as cg03456133, cg24440941 (
), cg20002843 (
, cg19107264, and cg11493553 located within the
gene and cg17065901 in
both susceptibility genes for type 2 diabetes and BMI, and cg23355087 within the
gene, known to be involved in insulin resistance during pregnancy.
Our study reveals the potential complexity of the epigenetic transmission between mothers with GDM and their offspring, likely determined by not only GDM exposure but also other factors indicated by maternal epigenetic status, such as maternal metabolic history.
Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent ...diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 × 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10-54), TCF7L2 (P = 4.0 × 10-16), CDKAL1 (P = 1.6 × 10-14), CDKN2A-CDKN2B (P = 4.1 × 10-9) and HKDC1 (P = 2.9 × 10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
Aims
We studied whether androgen excess and low sex hormone‐binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post‐prandial hyperglycaemia, gestational ...diabetes (GDM), and its severity.
Materials and Methods
This nationwide case–control study included 1045 women with GDM and 963 non‐diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early‐onset GDM (<20 gestational weeks) and the need for anti‐diabetic medication.
Results
After adjustments for gestational weeks at sampling, pre‐pregnancy BMI, and age, women with GDM had 3.7% (95% CI 0.1%–7.3%) lower SHBG levels, 3.1% (95% CI 0.1%–6.2%) higher T levels, and 4.6% (95% CI 1.9%–7.3%) higher FAI levels than controls. SHBG was inversely associated with fasting glucose, whereas higher FAI and T were associated with higher post‐prandial glucose concentrations. Women with early‐onset GDM had 6.7% (95% CI 0.7%–12.7%) lower SHBG levels and women who needed insulin for fasting hyperglycaemia 8.7% (95% CI 1.8%–14.8%) lower SHBG levels than other women with GDM.
Conclusions
Lower SHBG levels were associated especially with early‐onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post‐prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post‐prandial insulin secretion.
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