Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders.

Genetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. However, mtDNA sequencing is not routinely available in rapid genetic diagnosis programs, which may fail to diagnose mtDNA mutation-associated diseases. Herein, we explored the clinical utility of rapid exome sequencing combined with mtDNA sequencing in critically ill pediatric patients with suspected genetic disorders. Rapid clinical exome sequencing (CES) was performed as a first-tier test in 40 critically ill pediatric patients (aged from 6 days to 15 years) with suspected genetic conditions. Blood samples were also collected from the parents for trio analysis. Twenty-six patients presented with neuromuscular abnormalities or other systemic abnormalities, suggestive of suspected mitochondrial diseases or the necessity for a differential diagnosis of other diseases, underwent rapid mtDNA sequencing concurrently. A diagnosis was made in 18 patients (45.0%, 18/40); three cases with de novo autosomal dominant variants, ten cases with homozygous or compound heterozygous variants, three cases with hemizygous variants inherited from mother, three cases with heterozygous variants inherited from either parent, and one case with a mtDNA mutation. The 18 patients were diagnosed with metabolic (n = 7), immunodeficiency (n = 4), cardiovascular (n = 2), neuromuscular (n = 2) disorders, and others. Genetic testing reports were generated with a median time of 5 days (range, 3-9 days). Thirteen patients that were diagnosed had an available medical treatment and resulted in a positive outcome. We propose that rapid exome sequencing combined with mitochondrial DNA sequencing should be available to patients with suspected mitochondrial diseases or undefined clinical features necessary for making a differential diagnosis of other diseases.

Early Diagnosed Gestational Diabetes Mellitus Is Associated With Adverse Pregnancy Outcomes: A Prospective Cohort Study.

CONTEXT: The significance of an early diagnosis of gestational diabetes mellitus (GDM) with oral glucose tolerance test (OGTT) has not been determined. OBJECTIVE: The objective of this work is to investigate GDM diagnosed by early and standard OGTTs and determine adverse maternal and neonatal outcomes associated with early GDM diagnosis. RESEARCH DESIGN AND METHODS: The Early Diagnosis of Gestational Diabetes Mellitus study is a prospective cohort study. Each participant in the study underwent 2 OGTTs, an early OGTT at 18 to 20 gestational weeks (gws) and a standard OGTT at 24 to 28 gws. The reproduciblity between early and standard OGTT were analyzed. Maternal and neonatal metabolic disorders and pregnancy outcomes were compared across groups. RESULTS: A total of 522 participants completed both the early and standard OGTTs. The glucose values in the early OGTT were not significantly different from those in the standard OGTT (fasting: 4.31 ± 0.41 mmol/L vs 4.29 ± 0.37 mmol/L, P = .360; 1-hour: 7.68 ± 1.71 mmol/L vs 7.66 ± 1.59 mmol/L, P = .826; 2-hour: 6.69 ± 1.47 mmol/L vs 6.71 ± 1.39 mmol/L, P = .800). The reproducibility of early and standard OGTT results was 74.9%. Pregnant women in the GDM group had higher glycated hemoglobin, C-peptide, and homeostasis model assessment of insulin resistance in the late gestational period. Neonates born to mothers in the GDM group were at a higher risk of being large for gestational age (odds ratio [OR]: 3.665; 95% CI, 1.006-11.91) and were also more prone to neonatal hyperinsulinemia (OR: 3.652; 95% CI, 1.152-10.533). CONCLUSION: Early-onset GDM diagnosed by OGTT at 18 to 20 gws is associated with maternal and neonatal metabolic disorders and adverse pregnancy outcomes. Further randomized controlled trials on the therapeutic efficacy for early-onset GDM will confirm the significance of early screening for GDM.

Continuous elevation of plasma asprosin in pregnant women complicated with gestational diabetes mellitus: A nested case-control study.

INTRODUCTION: To investigate the expression of asprosin, a novel insulin resistance-related factor, in plasma and placenta of pregnant women with and without gestational diabetes mellitus (GDM). METHODS: This is a nested case-control study within the prospective study named Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM). Forty pregnant women with GDM and forty control cases with normal glucose tolerance (NGT) were recruited in the present study. Asprosin levels were tested by ELISA in maternal plasma at 18-20 and 24-28 gestational weeks and before delivery, as well as in umbilical plasma. Asprosin concentrations were compared between GDM and NGT groups, and the relationship between asprosin and other parameters were analyzed. Expression of asprosin in placenta was examined by Western blot and immunohistochemistry. RESULTS: Asprosin was elevated in plasma of GDM pregnant women and their offspring, after adjusted by maternal and neonatal clinical characteristics and lipid profiles. Asprosin was expressed in placenta from both GDM and NGT pregnant women. DISCUSSION: Protein asprosin is expressed in human placenta and is elevated in the plasma of pregnant women complicated with GDM and their offspring. As an insulin resistance-related factor increased before 20 gestational weeks, asprosin may play a role as a potential early biomarker of GDM.

The effect of exercise during pregnancy on gestational diabetes mellitus in normal-weight women: a systematic review and meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, and it has both short- and long-term adverse effects on the health of mothers and fetuses. To investigate the effect of exercise during pregnancy on the occurrence of GDM among normal-weight pregnant women. METHODS: We searched for studies published between January 1994 and June 2017 that appeared in the Web of Science, Scopus, ClinicalTrials.gov or Cochrane library databases. Randomized controlled trials that investigated the preventive effect of exercise on GDM in normal-weight women were included. Interventions including any confounding factors (e.g., dietary) were excluded. We extracted maternal characteristics, the diagnostic criteria of GDM, and basic information for intervention and obstetric outcomes. The primary outcome was the occurrence of GDM, and the secondary outcomes included gestational weight gain, gestational age at birth, birth weight, and the odds of cesarean section. A meta-analysis was conducted based on calculations of pooled estimates using the random-effects model. RESULTS: Eight studies were included in this systematic review and meta-analysis. Exercise during pregnancy was shown to decrease the occurrence of GDM [RR = 0.58, 95% CI (0.37, 0.90), P = 0.01 and RR = 0.60, 95% CI (0.36, 0.98), P = 0.04 based on different diagnosis criteria, respectively] in normal-weight women. Regarding secondary outcomes, exercise during pregnancy can decrease gestational weight gain [MD = - 1.61, 95% CI (- 1.99, - 1.22), P<0.01], and  had no significant effects on gestational age at birth [MD = - 0.55, 95% CI (- 1.57, 0.47), P = 0.29], birth weight [MD = - 18.70, 95% CI (- 52.49, 15.08), P = 0.28], and the odds of caesarean section [RR = 0.88, 95% CI (0.72, 1.08), P = 0.21], respectively. CONCLUSIONS: Exercise during pregnancy can ostensibly decrease the occurrence of GDM without reducing gestational age at delivery and increasing the odds of cesarean section in normal-weight women.

The associations between triglyceride to high-density lipoprotein cholesterol ratios and the risks of gestational diabetes mellitus and large-for-gestational-age infant.

OBJECTIVE: To evaluate the associations between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratios and the risks of gestational diabetes mellitus (GDM) and delivering large-for-gestational-age (LGA) infant. DESIGN: This was a single-centre prospective observational study. PATIENTS: Six hundred and thirty-six women with a singleton pregnancy were recruited. MEASUREMENTS: Lipids profile, HbA1c and glucose were measured at the time of oral glucose tolerance test (OGTT) during 24-28 gestational weeks. TG/HDL-C ratios were calculated and clinical data including perinatal parameters were analysed. RESULTS: The prevalence of GDM was 17·30% (n = 110) and LGA was 3·93% (n = 25) in this study. TG/HDL-C ratios were found to be significantly higher in GDM group (P < 0·01) and LGA group (P = 0·045) compared with those in non-GDM group and non-LGA group, respectively. TG/HDL-C ratios were independently associated with the risks of GDM (OR = 1·64, P = 0·02) and LGA (OR = 2·87, P < 0·01). The area under the combined ROC curve of TG/HDL-C ratio and HbA1c to detect GDM was 0·705 (95% CI, 0·637-0·772). Furthermore, the area under the ROC curve of TG/HDL-C ratio combined with HbA1c and prepregnancy BMI to detect LGA was 0·806 (95% CI, 0·719-0·893). CONCLUSIONS: TG/HDL-C ratios in combination with HbA1c and prepregnancy BMI can be good markers to predict the risks of GDM and delivering LGA infant.

Fetal growth is associated with maternal fasting plasma glucose at first prenatal visit.

AIMS: Fasting plasma glucose (FPG) concentration measured at the first prenatal visit is a predictor of gestational diabetes mellitus (GDM); however, whether this test is indicative of fetal growth has not been clarified. Thus, the purpose of this study was to determine whether birth weight and birth length were related to FPG levels at the first prenatal visit. MATERIALS AND METHODS: Research samples were collected from pregnant women who took an FPG test at their first prenatal visit (10-24 gestational weeks), received regular prenatal care, and delivered in our center. FPG value, maternal pre-gravid BMI, weight gain before FPG test, before and after Oral Glucose Tolerance Test (OGTT), neonatal birthweight, birth length, Ponderal Index and birthing method were recorded for analysis. Data were analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation or logistic regression to confirm differences. Statistical significance level was α = 0.05. RESULTS: 2284 pregnant women, including 462 GDM and 1822 with normal glucose tolerance (NGT) were recruited for the present study. FPG concentration at the first prenatal visit was associated with neonatal birth weight (partial correlation coefficient r' = 0.089, P<0.001) and birth length (partial correlation coefficient r' = 0.061, P = 0.005), but not with Ponderal Index or birthing method. Maternal pre-gravid BMI was associated with FPG value (partial correlation coefficient r' = 0.113, P<0.001). FPG concentration at the first prenatal visit (OR = 2.945, P<0.001), weight gain before OGTT test (OR = 1.039, P = 0.010), and age (OR = 1.107, P<0.001) were independent related factors of GDM. CONCLUSION: Fasting plasma glucose concentration at the first prenatal visit is associated with fetal growth. Maternal pre-gravid BMI and weight gain are related to glucose metabolism.