Previous studies have demonstrated that gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2D) share common genetic polymorphisms. We conducted meta-analysis and subgroup analysis of ...all available variants and determined the effects of confounding and experimental components on the genetic association of GDM. Any case-controlled or cohort studies with genotype distribution compared GDM cases with controls were included. In total, 28 articles including 8,204 cases and 15,221 controls for 6 polymorphisms were studied. rs10830963(MTNR1B), rs7903146(TCF7L2), and rs1801278(IRS1) were significantly associated with the increased GDM risk. The association of rs4402960(IGF2BP2) and rs1800629(TNF-α) was significant only when the studies with control allele frequency deviation and publication bias were excluded. Further subgroup analysis showed the risk alleles of rs7903146(TCF7L2) and rs1801282(PPARG) were significantly associated with the GDM risk only in Asian, but not in Caucasian population. The OGTT test using 100 g, but not 75 g; and genotype detection by other assays, but not Taqman method, were also significantly associated with increased GDM risk in rs1801278(IRS1) and rs7903146(TCF7L2). Overall GDM was associated with rs10830963(MTNR1B), rs7903146(TCF7L2), and rs1801278(IRS1), but only rs7903146(TCF7L2) and rs1801282(PPARG) were significant in Asian populations. While rs1801278(IRS1) and rs7903146(TCF7L2) were significantly affected by OGTT protocol and genotyping methods.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The progression to type 2 diabetes mellitus (DM) and other long-term cardiometabolic risks in Chinese women with prior history of gestational diabetes (GD) was studied at 15 years postpartum.
139 ...Chinese women (45 with GD and 94 with normal glucose tolerance (NGT) at the index pregnancy) who had their insulin sensitivity and β-cell functions examined at 8 years postpartum were again followed up at 15 years for the investigation of the rate of type 2 DM, hypertension and metabolic syndrome.
Women with prior history of GD had a significantly higher rate of hypertension (35.6% vs. 16.0%, p = 0.01), type 2 DM (24.4% vs. 5.3%, p < 0.001) and impaired glucose regulation (26.6% vs. 14.9%, p < 0.001) than women with NGT during the index pregnancy. The Matsuda insulin sensitivity index and the quantitative insulin sensitivity check index at 8 years postpartum were independent predictors of both DM and metabolic syndrome at 15 years postpartum.
The conversion rate of type 2 DM increased at an average rate of 1.6% per year after a pregnancy affected by GD. Insulin resistance at 8 years postpartum could refine a future diabetic risk in women with prior history of GD.
Objective To compare in twin pregnancy the rate of deterioration in umbilical blood gas status during the second stage of labour, and to investigate whether the duration of the first twin's delivery ...has any effect on the blood gas status of the second twin.
Design A retrospective study.
Setting Department of Obstetrics and Gynaecology in a university teaching hospital.
Population Twin pregnancies with both of the twins delivered by normal cephalic vaginal mode, at or beyond 34 weeks of gestation, over a period of seven years. Twins with any maternal or fetal complications including discordant growth, intrauterine growth restriction, intrauterine death, fetal malformations, fetal distress, pre‐eclampsia and diabetes were excluded.
Methods The first twins' second stage was defined as from the start of maternal pushing to his/her delivery, while the second twins' second stage started after the delivery of the first twin and ended by his/her delivery. The total duration of the second stage was the sum of the above two intervals. The correlations between the first twins' umbilical cord blood gas parameters and the duration of their own second stage, the second twins' umbilical cord blood gas parameters and the duration of their own second stage, as well as that of the total second stage, were studied.
Main outcome measures The changes of umbilical arterial pH of each twin with the duration of the corresponding second stage of labour, and the difference among them.
Results A total of 51 cases were reviewed. The median gestation at delivery was 37 weeks. The median duration of first twins' second stage was 10 minutes (range 1–75) while that of the second twins' was 10 minutes (range 3–26). The first twins' second stage was inversely correlated with their arterial pH, venous pH and base excess BE (P < 0.01). Both the second twins' second stage and the total second stage were inversely correlated with both of their arterial and venous pH and BE (P < 0.01). However, further multiple regression analysis suggested that the correlation of the total second stage with the second twins' cord blood parameters could be solely explained by their own second stage. The rate of reduction in the second twins' arterial pH was 4.95 × 10−3 per minute, and was significantly faster than that of the first twins', which was 1.55 × 10−3 per minute (P < 0.05).
Conclusions During normal vaginal delivery, the umbilical cord blood gas status of both the first and the second twins deteriorated with the duration of their corresponding second stages, but the effects are greater in the latter. Furthermore, the duration of the first twins' second stage does not affect the blood gas status of the second twins'. These observations support the postulation of a diminished uteroplacental exchange function after the delivery of the first twin. Close monitoring and expeditious delivery of the second twins are important.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Clinical experience suggests that diverse clinical subtypes exist within the broader diagnosis of GDM. Analysis from a single centre recently outlined heterogeneity in GDM with ...respect to insulin secretion and sensitivity, defining four GDM subtypes: 1) GDMsecr (<25th centile HOMA-β (Hb) for non-GDM); 2) GDMsens (<25th centile Matsuda Index for non-GDM); 3) GDMmixed (both GDMsecr and GDMsens); 4) GDMND, no defect (neither GDMsecr and GDMsens). Classification using these subtypes is associated with adverse outcomes.
Methods
Following similar methodology, women with GDM were classified into four subtypes including comparison of Hb, insulinogenic index (II) and Stumvoll first-phase estimate (SV) for defining GDMsecr. Analyses compared neonatal outcomes with non-GDM women and between GDM groups using c2 tests and regression analyses adjusted for multiple confounders including maternal age, BMI and HAPO study centre.
Results
Hb, II and SV gave divergent results for GDMsecr, with only 19% concordance. In all analyses, GDMND (10% by Hb, 6% by II, 6% by SV) showed outcome frequencies similar to those of non-GDM women; groups 1-3 showed higher risks (p < 0.01 vs non GDM). These results persisted in the fully adjusted model (aOR generally >2.0).
Conclusions
Different clinical subtypes in GDM are associated with differing risks of adverse outcome.
Key messages
Determination of GDM subtype can assist in assessing GDM women at higher risk of adverse clinical outcome and help guide clinical practice.
Objective
The aim was to study the association between newborn anthropometrics and childhood cardiovascular risks and whether newborn anthropometrics mediate the effect of maternal gestational weight ...gain (GWG) on childhood risks.
Methods
Data of 926 mother–child dyads from the Hyperglycemia and Adverse Pregnancy Outcomes study were analyzed. Newborn anthropometrics were treated as predictors and mediators by using a regression model and causal mediation model, respectively.
Results
Newborn sum of skinfolds (SSF) was associated with childhood diastolic blood pressure (DBP) and pulse wave velocity (coefficients 95% CI: 0.13 0.06 to 0.20; 0.08 0.004 to 0.15), whereas newborn ponderal index (PI) was inversely associated with childhood systolic blood pressure (SBP), DBP, and pulse wave velocity (−0.08 −0.15 to −0.01; −0.08 −0.14 to −0.008; −0.09 −0.16 to −0.03). Newborn SSF mediated the effects of maternal excessive GWG on childhood SSF and DBP (proportion of total effect 9% and 8%, respectively). In contrast, a significant negative mediation through newborn PI was found for the effect of maternal excessive GWG on childhood DBP (−8%) and its effect on childhood SBP through birth weight (−27%).
Conclusions
Childhood cardiovascular risks are positively associated with newborn SSF but inversely associated with newborn PI. Newborn SSF mediates the impact of excessive maternal GWG on childhood BP, but birth weight and newborn PI negatively mediate it.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND: When compared with the conventional surgical evacuation for the treatment of miscarriage, medical evacuation has been largely accepted as an effective and safe management. However, there ...is a lack of data on the long-term reproductive outcome of these two treatment modalities, which is crucial in patient counselling. The current study evaluates and compares the long-term fertility and pregnancy outcome following these two treatments. METHODS: A cohort of 604 women enrolled in a previous randomized controlled trial comparing medical and surgical evacuation for miscarriage were followed up prospectively by telephone interview at a median of 6 (range 4–9) years using a structured questionnaire. RESULTS: A total of 423 women were contacted and four declined to participate (response rate 69.4%). Of these, 261 women (131 medical and 130 surgical evacuations) had attempted to become pregnant since the miscarriage. There were no differences in their baseline characteristics including age, reproductive and contraceptive history. The natural conception rates were the same (97.7%, P = 0.99) and the cumulative pregnancy rates were similar between groups, being 60 and 80% at 12 and 24 months respectively. The median time-to-pregnancy was 8 months in both groups (P = 0.97) and the subsequent live birth rates (85.2 versus 88.2%, P = 0.72) resulting from the immediate pregnancy following previous treatment were similar. CONCLUSIONS: The long-term conception rate and pregnancy outcome are not different following medical or surgical evacuation for miscarriage. Women should be reassured that their long-term fertility potential will not be compromised after medical treatment.
This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.
HAPO was an observational ...international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10-14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT.
Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased.
Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern ...Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.
Nine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).
The nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G p.Asn78Ser, c.239G > T p.Ser80Ile, c.319C > G p.Arg107Gly, c.481C > T p.Arg161X, c.482G > A p.Arg161Gln, c.499C > T p.Arg167Trp and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.
Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.
Introduction
Adolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective ...case–control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS.
Methods
The study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle <6°). Clinical and radiological assessments were conducted on each group.
Results
Cobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%,
p
= 0.027) and arm lean mass (8.9%,
p
< 0.050), weaker dominant handgrip strength (8.8%,
p
= 0.027), deranged cortical compartment lower volumetric bone mineral density (vBMD) by 6.5%,
p
= 0.002, and lower bone mechanical properties stiffness and estimated failure load lowered by 13.2% (
p
= 0.005) and 12.5% (
p
= 0.004). The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity,
p
= 0.011).
Discussion
Patients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression.
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