Dietary patterns during pregnancy and maternal and birth outcomes in women with type 1 diabetes: the Environmental Determinants of Islet Autoimmunity (ENDIA) study.

AIMS/HYPOTHESIS: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. METHODS: Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. RESULTS: Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a 'fresh food' dietary pattern than women without type 1 diabetes (OR 1.19, 95% CI 1.07, 1.31; p=0.001). In women with type 1 diabetes, an increase equivalent to a change from quartile 1 to 3 in 'fresh food' dietary pattern score was associated with a lower risk of pre-eclampsia (OR 0.37, 95% CI 0.17, 0.78; p=0.01) and premature birth (OR 0.35, 95% CI 0.20, 0.62, p<0.001). These associations were mediated in part by BMI and HbA1c. The 'processed food' dietary pattern was associated with an increased birthweight (ß coefficient 56.8 g, 95% CI 2.8, 110.8; p=0.04). Physical activity did not relate to outcomes. CONCLUSIONS/INTERPRETATION: A dietary pattern higher in fresh foods during pregnancy was associated with sizeable reductions in risk of pre-eclampsia and premature birth in women with type 1 diabetes.

Insulin requirements during pregnancy in women with type 1 diabetes treated with insulin pump.

INTRODUCTION: Insulin requirement in women with Type 1 diabetes (T1DM) changes throughout pregnancy. The aim of this study was to determine the total change in insulin requirements and the effect of gestational weight gain (GWG) and pre-gestational BMI on insulin requirements during pregnancy in women with T1DM treated with continuous subcutaneous insulin infusion and continuous glucose monitoring. METHODS: This historical cohort study included all consecutive women with T1DM who were monitored during pregnancy at the high-risk pregnancy clinic at a tertiary medical center during April 2011-April 2019. One Way Repeated Measures ANOVA with Bonferroni adjustment was conducted to compare the effects of gestational age on insulin requirements and a Two Way Repeated Measures ANOVA was employed to test for the interaction between gestational age intervals and maternal BMI and GWG. RESULTS: Data regarding insulin requirements of 185 pregnancies were included in the analyses. There was a significant effect of gestational age on total insulin (Wilks' Lambda = 0.34, F(6,14) = 4.52, p = 0.009), basal insulin (Wilks' Lambda = 0.41, F(6,14) = 3.30, p = 0.031) and bolus insulin (Wilks' Lambda = 0.43, F(6,14) = 3.02, p = 0.041). Total insulin/kg requirements increased by 5.5% from 13-20 weeks to 20-26 weeks, 19% from 20-26 weeks to 26-33 weeks, and 17.4% from 26 to 33 weeks to delivery (p for trend = 0.009). Overall, insulin requirements increased by 42.1% from conception to delivery (p < 0.01). There was no significant main effect of maternal BMI or GWG on insulin requirements. CONCLUSIONS: There is a significant increase in insulin requirements per kg during pregnancy in women with T1DM who were treated with an insulin pump.

Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Maternal Diabetes and Risk of Hypospadias: A Systemic Review and Meta-Analysis.

INTRODUCTION: This study aimed to investigate the association between maternal diabetes and the risk of hypospadias in male infants, as the relationship between them remains uncertain. METHODS: To comprehensively evaluate the association between pregestational diabetes mellitus and gestational diabetes mellitus with hypospadias, we conducted a systematic review and meta-analysis. A thorough literature search was conducted, encompassing relevant publications published prior to January 2023. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our meta-analysis comprised a total of 13 studies, 11 of which investigated the relationship between pregestational diabetes mellitus and hypospadias, while 9 studies explored the association between gestational diabetes mellitus and hypospadias. Notably, these investigations yielded compelling evidence of significant positive associations between pregestational diabetes mellitus and hypospadias (OR = 1.51, 95% CI = 1.13-2.03), as well as between gestational diabetes mellitus and hypospadias (OR = 1.18, 95% CI = 1.04-1.35). CONCLUSION: Our findings suggest that both pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring. Further investigations are needed to explore the optimal range of blood glucose during pregnancy that minimizes the risk of congenital malformation in the fetus, as well as to develop more effective measures for glycemic control in pregnant women.

Progression of diabetic retinopathy in women with pregestational diabetes during pregnancy and postpartum.

BACKGROUND: Diabetic retinopathy (DR) may worsen during pregnancy, but its course in the postpartum remains poorly understood. Understanding the natural history of DR during and after pregnancy can help determine when sight-threatening DR treatment should be administered. METHODS: A prospective longitudinal cohort study recruited pregnant women with pre-existing type 1 (T1D) or type 2 diabetes from two tertiary Diabetes Antenatal Clinics in Melbourne, Australia. Eye examination results in early pregnancy, late pregnancy, and up to 12-months postpartum were compared to determine DR changes. Two-field fundus photographs and optical coherence tomography scans were used to assess DR severity. RESULTS: Overall, 105 (61.4%) women had at least two eye examinations during the observation period. Mean age was 33.5 years (range 19-51); 54 women (51.4%) had T1D; 63% had HbA1c <7% in early pregnancy. DR progression rate was 23.8% (95% CI 16.4-32.6). Having T1D (RR 4.96, 95% CI 1.83-13.46), pre-existing DR in either eye (RR 4.54, 95% CI 2.39-8.61), and elevated systolic blood pressure (adjusted RR 2.49, 95% CI 1.10-5.66) were associated with increased risk of progression. Sight-threatening progression was observed in 9.5% of women. Among the 19 eyes with progression during pregnancy, 15 eyes remained stable, three eyes progressed, and only one eye regressed in the postpartum. CONCLUSIONS: Nearly 1 in 4 women had DR progression from conception through to 12-months postpartum; almost half of these developing sight-threatening disease. DR progression occurring during pregnancy was found to predominantly remain unchanged, or worsen, after delivery, with very few eyes spontaneously improving postpartum.

Role of Cerebroplacental Ratio in Predicting the Outcome of Pregnancies Complicated by Diabetes.

INTRODUCTION: Our objective was to evaluate the strength of association and diagnostic performance of cerebroplacental ratio (CPR) in predicting the outcome of pregnancies complicated by pre- and gestational diabetes mellitus. METHODS: PubMed, Embase, Cochrane, and Google Scholar databases were searched. Inclusion criteria were pregnancies complicated by gestational or pregestational diabetes undergoing ultrasound assessment of CPR. The primary outcome was a composite score of perinatal mortality and morbidity as defined by the original publication. The secondary outcomes included preterm birth gestational age (GA) at birth, mode of delivery, fetal growth restriction (FGR) or small for GA (SGA) newborn, neonatal birthweight, perinatal death (PND), Apgar score <7 at 5 min, abnormal acid-base status, neonatal hypoglycemia, admission to neonatal intensive care unit (NICU). Furthermore, we aimed to perform a number of sub-group analyses according to the type of diabetes (gestational and pregestational), management adopted (diet insulin or oral hypoglycemic agents), metabolic control (controlled vs. non-controlled diabetes), and fetal weight (FGR, normally grown, and large for GA fetuses). Head-to-head meta-analyses were used to directly compare the risk of each of the explored outcomes. For those outcomes found to be significant, computation of diagnostic performance of CPR was assessed using bivariate model. RESULTS: Six studies (2,743 pregnancies) were included. The association between low CPR and adverse composite perinatal outcome was not statistically significant (p = 0.096). This result did not change when stratifying the analysis using CPR cut-off below 10th (p = 0.079) and 5th (p = 0.545) centiles. In pregnancies complicated by GDM, fetuses with a low CPR had a significantly higher risk of birthweight <10th percentile (OR: 5.83, 95% confidence interval [CI] 1.98-17.12) and this association remains significant when using a CPR <10th centile (p < 0.001). Fetuses with low CPR had also a significantly higher risk of PND (OR: 6.15, 95% CI 1.01-37.23, p < 0.001) and admission to NICU (OR 3.32, 95% CI 2.21-4.49, p < 0.001), but not of respiratory distress syndrome (p = 0.752), Apgar score <7 at 5 min (p = 0.920), abnormal acid-base status (p = 0.522), or neonatal hypoglycemia (p = 0.005). These results were confirmed when stratifying the analysis including only studies with CPR <10th centile as a cut-off to define abnormal CPR. However, CPR showed a low diagnostic accuracy for detecting perinatal outcomes. CONCLUSION: CPR is associated but not predictive of adverse perinatal outcome in pregnancies complicated by gestational diabetes. The findings from this systematic review do not support the use of CPR as a universal screening for pregnancy complication in women with diabetes.

Fetal Strain and Strain Rate Measured with Speckle Tracking Echocardiography in Maternal Diabetes: Systematic Review.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate fetal cardiac function in fetuses of mothers with diabetes compared to those of mothers without diabetes using 2D-STE. METHODS: Embase, MEDLINE, and CENTRAL were searched for observational studies on 2D-STE fetal left and right ventricular global longitudinal strain and strain rate that included singleton, non-anomalous pregnancies complicated by pregestational or gestational diabetes mellitus compared to uncomplicated pregnancies. The strain values were pooled per 4 weeks of gestation for meta-analysis using random-effects models. RESULTS: Fifteen studies met the criteria, including 990 fetuses of diabetic mothers and 1,645 control fetuses. The study design was cross-sectional in fourteen studies and longitudinal in one study. Gestational age, type of diabetes, ultrasound device, and 2D-STE software varied between the studies. Glycemic control and type of treatment were often lacking. In fetuses of diabetic mothers versus healthy mothers, left ventricular strain was significantly decreased (7 studies), increased (1 study), or not significantly different (7 studies). Right ventricular strain was decreased (7 studies), increased (1 study), or not different (2 studies). Left ventricular strain rate was decreased (3 studies), increased (1 study), or not different (2 studies). Right ventricular strain rate was increased (1 study) or not different (2 studies). CONCLUSION: Fetuses of mothers with diabetes show evidence of systolic dysfunction, which is more visible in the right ventricle. Contradictory results are probably due to suboptimal study designs and variation in gestational age, diabetes severity, image acquisition, and software. Large prospective longitudinal studies are needed to assess fetal myocardial function with 2D-STE in pregestational diabetes mellitus type 1 and 2 and gestational diabetes mellitus pregnancies. The influence of glycemic control, BMI, and treatment should be evaluated.

Utility of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in pregestational diabetes: A prospective cohort study.

PURPOSE: To examine the cerebro-placental-uterine ratio (CPUR) in pregnant women with pregestational diabetes and determine its role in predicting adverse prenatal outcomes. METHODS: This prospective, cohort study conducted at a tertiary hospital included 65 patients with pregestational diabetes (25 with type1 diabetes, 40 with type2 diabetes) and 130 low-risk patients in the control group. The cerebroplacental (CPR) ratio and the CPUR were calculated. Composite adverse perinatal outcome (CAPO) is defined as the presence of any of the following: (1) Neonatal intensive care unit (NICU) admission, (2) Apgar at 5 min <7, and (3) umbilical cord arterial pH <7.10. The relationship of CPR and CPUR with CAPO was investigated. RESULTS: CPR and CPUR were significantly lower in the pregestational diabetes group than in the control group. The NICU admission was higher in the case group. In receiver operating characteristic analyses, the optimal cut-off value of CPUR was 1.46 (AUC = 0.72, p = 0.003, 80% sensitivity, and 69% specificity) to predict CAPO and the optimal cut-off value of CPUR was 1.50 for NICU admission (AUC = 0.70, p = 0.013, 77% sensitivity, and 66% specificity). CONCLUSION: Low CPUR values were found to be associated with adverse perinatal outcomes in women with pregestational diabetes. With the increasing number of studies, CPUR is expected to be utilized more widely in routine obstetric practice.

Associations between maternal metabolic conditions and neurodevelopmental conditions in offspring: the mediating effects of obstetric and neonatal complications.

BACKGROUND: Maternal pre-gestational diabetes (PGDM), gestational diabetes mellitus (GDM), and overweight/obesity have been associated with increased risks of offspring neurodevelopmental conditions (NDCs) including autism, intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). Less is known about whether and how obstetric and neonatal complications (e.g., preterm birth, neonatal asphyxia) could mediate these associations. METHODS: In this Swedish register-based cohort study, we examined complications during pregnancy, delivery, and the neonatal period as potential mediators of the relationships between maternal metabolic conditions and offspring NDCs. We quantified the extent to which these obstetric and neonatal factors could mediate the associations of maternal metabolic conditions with offspring NDCs by applying parametric regression models for single mediation analyses and weighting-based methods for multiple mediation analyses under counterfactual frameworks. RESULTS: The study sample included 2,352,969 singleton children born to 1,299,692 mothers from 1987-2010 who were followed up until December 31, 2016, of whom 135,832 children (5.8%) were diagnosed with at least one NDC. A substantial portion of the association between maternal PGDM and children's odds of NDCs could be explained by the combined group of obstetric and neonatal complications in the multiple mediation analysis. For instance, these complications explained 44.4% of the relationship between maternal PGDM and offspring ID risk. The proportion of the relationship between maternal overweight/obesity and children's risk of NDCs that could be explained by obstetric and neonatal complications was considerably smaller, ranging from 1.5 to 8.1%. Some complications considered on their own, including pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities, could explain at least 10% of the associations between maternal PGDM and offspring NDCs. Complications during the neonatal period showed a stronger joint mediating effect for the relationship between PGDM and offspring NDCs than those during pregnancy or delivery. CONCLUSIONS: Obstetric and neonatal complications could explain nearly half of the association between maternal PGDM and offspring risk of NDCs. The mediating effects were more pronounced for complications during the neonatal period and for specific complications such as pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities. Effective preventive strategies for offspring NDCs should holistically address both the primary metabolic issues related to PGDM and the wide array of potential complications, especially those in the neonatal period.

Trends in delivery hospitalizations with pregestational and gestational diabetes mellitus and associated outcomes: 2000-2019.

BACKGROUND: Pregestational diabetes mellitus and its associated risks may be increasing in the obstetrical population. OBJECTIVE: This study aimed to characterize the trends in delivery hospitalizations with pregestational diabetes mellitus, the prevalence of chronic diabetes complications, and the risk for adverse outcomes. STUDY DESIGN: This repeated, cross-sectional study used the United States National Inpatient Sample to identify delivery hospitalizations with pregestational diabetes mellitus between 2000 and 2019. Trends in delivery hospitalizations with pregestational diabetes mellitus were assessed using joinpoint regression to determine the average annual percent change. Trends in chronic diabetes complications, including chronic kidney disease, neuropathy, peripheral vascular disease, and diabetic retinopathy, were also analyzed. The risk for adverse obstetrical outcomes was compared between patients with and those without pregestational diabetes mellitus using adjusted logistic regression models that were adjusted for demographic, clinical, and hospital characteristics with adjusted odds ratios with 95% confidence intervals as measures of association. RESULTS: Of 76.7 million delivery hospitalizations, 179,885 (0.23%) had type 1 diabetes mellitus, 430,544 (0.56%) had type 2 diabetes mellitus, and 99,327 (0.13%) had unspecified diabetes mellitus. From 2000 to 2019, the prevalence of diabetes mellitus increased from 1.8 to 7.3 per 1000 deliveries for type 2 diabetes mellitus (average annual percent change, 8.0%; 95% confidence interval, 6.9%-9.2%), from 1.5 to 3.2 per 1000 deliveries for unspecified diabetes mellitus (average annual percent change, 3.9%; 95% confidence interval, 1.4%-6.3%), and from 2.7 in 2000 to 2.8 per 1000 deliveries (average annual percent change, 0.2%; 95% confidence interval, -0.8% to 1.3%) for type 1 diabetes mellitus. The prevalence of chronic diabetes mellitus complications increased from 2.7% to 5.6% over the study period (average annual percent change, 5.9%; 95% confidence interval, 3.7%-8.0%). Pregestational diabetes mellitus was associated with severe maternal morbidity, cesarean delivery, hypertensive disorders of pregnancy, preterm birth, and shoulder dystocia. CONCLUSION: Pregestational diabetes mellitus increased over the study period, driven by a quadrupling in the prevalence of type 2 diabetes mellitus. Notably, the prevalence of chronic diabetes mellitus complications doubled concomitantly. Pregestational diabetes mellitus was associated with a range of adverse outcomes. These findings are further evidence that pregestational diabetes mellitus is an important contributor to maternal risk and that optimizing diabetes care in women of childbearing age will continue to be of major public health importance.

Intrapartum continuous subcutaneous insulin infusion vs intravenous insulin infusion among pregnant individuals with type 1 diabetes mellitus: a randomized controlled trial.

BACKGROUND: Intrapartum glucose management is critical to reducing neonatal hypoglycemia shortly after birth. Although it is known that insulin is required for all pregnant individuals with type 1 diabetes mellitus, the optimal mode of intrapartum glycemic control is not known. OBJECTIVE: This study aimed to compare the effect of intrapartum use of continuous subcutaneous insulin infusion with that of intravenous insulin infusion for glucose management among pregnant individuals with type 1 diabetes mellitus on neonatal blood glucose levels. STUDY DESIGN: This was a randomized controlled trial of pregnant participants with type 1 diabetes mellitus. After written informed consent, participants were randomly allocated to 1 of 2 intrapartum insulin administration strategies: continuation of their continuous subcutaneous insulin infusion or intravenous insulin infusion. The primary outcome was the first neonatal blood glucose level. RESULTS: Between March 2021 and April 2023, 76 participants were approached, and 70 participants were randomized (35 participants in the intravenous insulin infusion group and 35 participants in the continuous subcutaneous insulin infusion group). The groups were similar in terms of age, race/ethnicity, pregravid body mass index, nulliparity, and gestational age at delivery. There was no statistically significant difference in the first neonatal glucose measurement between the 2 groups (50.1±23.4 vs 49.2±22.6; P=.86). In addition, there were no statistically significant differences in any secondary neonatal outcomes. Approximately 57.1% of neonates in the continuous subcutaneous insulin infusion group required either oral, intravenous, or both treatments for hypoglycemia, whereas 51.4% of neonates in the intravenous infusion group required treatment. In both groups, 28.6% of neonates required intravenous treatment for hypoglycemia. CONCLUSION: Pregnant individuals with type 1 diabetes mellitus using either intravenous insulin infusion or continuation of their continuous subcutaneous insulin infusion for intrapartum insulin administration had no difference in the primary outcome of neonatal hypoglycemia. Patients should be given the option of both glycemic management strategies intrapartum.

Effect of glycemic control on fetal hearts of pregestational diabetic women by tissue doppler and M-mode imaging.

OBJECTIVE: To determine whether changes in fetal heart function according to glycemic control in pregnant women with Type 1 and Type 2 diabetes using spectral tissue Doppler imaging (TDI) and M-mode imaging. METHODS: This study included 68 pregestational diabetic women (DM) at 30-32 gestational weeks. All participants were divided into two groups: type 1(n = 17) and type 2(n = 51), and then these groups were divided into the subgroups as well-controlled and poorly controlled, according to fasting glucose (FG) and 1-h postprandial glucose (PPG) values. Cardiac parameters were compared for well- and poorly-controlled groups with TDI and M-mode imaging. The correlation of cardiac parameters with FG, PPG, and HbA1c values was evaluated. Their roles in predicting neonatal outcomes were also assessed. RESULTS: Thickness measurements, early diastolic annular peak velocity (E'), late diastolic annular peak velocity (A'), tissue isovolumetric relaxation time (IRT'), and tissue myocardial performance index (MPI') were increased in both poorly controlled groups. Tissue ejection time (ET') was significantly reduced in the poorly controlled groups, while tissue isovolumetric contraction time (ICT') was not significantly changed in any group. Tricuspid, mitral, and septal annular plane excursions (TAPSE, MAPSE, and SAPSE, respectively) were significantly decreased in all poorly controlled subgroups. E', E'/A', MPI', IRT', ET', and M-mode imaging parameters significantly correlated with FG notably. CONCLUSION: Maternal hyperglycemia leads to subtle changes in systolic and diastolic functions both in the interventricular septum and ventricles, so it is essential to ensure glycemic control in both Type 1 and Type 2 DM.

Ultrasound-Guided Prospective Screening for Spinal Dysraphism in Offspring of Mothers With Pregestational Diabetes: A Pilot Study.

AIM: Determine the utility of prospective spinal ultrasound in infants of mothers with pregestational diabetes (PGDM) for the diagnosis of closed spinal dysraphism (SDs). METHODS: This prospective observational pilot study was completed at a tertiary care center between May 1, 2020 and December 30, 2022. Infants born to mothers with PGDM and with normal spinal physical examinations were included. A total of 25 mother-infant dyads were enrolled in the study and prospectively screened with spinal ultrasound. The study was registered on ClinicalTrials.gov (Identifier-NCT05033275). RESULTS: Twenty-five spinal ultrasounds were performed over the course of this study with three (8%) resulting in abnormal findings that required further imaging. Follow-up with magnetic resonance imaging found one case of tethered cord syndrome. CONCLUSION: Prospective screening in infants of mothers with PGDM found one case of tethered cord syndrome. This finding suggests that risk stratified screening of mothers with diabetes might be a reasonable approach to care.

Changes in fetal intracranial anatomy during maternal pregestational and gestational diabetes.

AIM: To evaluate the changes in fetal intracranial structures in pregnant women with pregestational diabetes mellitus (DM) and gestational diabetes mellitus (GDM). METHODS: The study was conducted prospectively with patients who were grouped as pregestational DM (n = 110), GDM (n = 110), and control (n = 110). Fetal ultrasonographic measurements of widths of posterior lateral ventricles (PLV), cavum septum pellucidi (CSP), cisterna magna (CM), thalamus and transcerebellar diameter (TCD) were recorded and compared. RESULTS: Fetal PLV, CSP, and CM widths were higher in pregestational DM and GDM groups than in control group, and also higher in pregestational DM group compared to GDM group (p < 0.001). Fetal TCD in the PGDM group was found to be less than both control and GDM groups (p < 0.001). No difference was found between three groups in terms of fetal thalamus size (p = 0.801). Fetal PLV, CSP, and CM values were positively correlated with maternal hyperglycemia, fetal abdominal circumference (AC), and deepest vertical pocket of amniotic fluid (DVP) (p < 0.001). Fetal TCD was negatively correlated with HbA1c and DVP (p = 0.002, p = 0.38, respectively). The optimal cut-off points to identify pregestational DM and GDM were 5.55 and 5.83 mm for PLV, 5.83 and 6.32 mm for CSP, and 7.26 and 6.62 mm for CM. CONCLUSION: Maternal hyperglycemia was significantly associated with an increase in the widths of fetal PLV, CSP, and CM and a decrease in fetal TCD.

Can diabetes influence fetal thymus size during pregnancy?

OBJECTIVE: The aim of the study was to evaluate fetal thymus size by sonography in diabetic pregnancies and its relationship with diabetes type. METHODS: In this prospectively designed case-control study, fetal thymus transverse diameter and circumference of the fetal thymus were measured. Also, TTR (thymic-thoracic ratio) was assessed in 288 healthy and 105 diabetic pregnancies. Patients were divided into subgroups as diet-controlled gestational diabetes (GDMA1, n = 40), insulin-dependent (GDMA2, n = 42), and pregestational diabetes mellitus (PGDM, n = 23). GDM was diagnosed between 24 and 28 weeks of gestation with a 75 g oral glucose tolerance test. Measurements were compared to the healthy control group. Pairwise comparisons with Bonferroni correction determined which type of diabetes was independently associated with a small fetal thymus. RESULTS: All 3 maternal diabetes categories had smaller fetal thymus size than controls (p < 0.05). TTR were lowest in PGDM (p < 0.05). CONCLUSION: Gestational diabetes is associated with smaller fetal thymus size. Pregestational diabetes may be associated with a smaller fetal thymus compared to diet-controlled GDM. Also, the thymus size may be even smaller in those with poor blood glucose regulation.

Does diabetes mellitus affect the development of fetal brain structures and spaces including corpus callosum, subarachnoid space, insula, and parieto-occipital fissure?

PURPOSE: We investigated the impact of pregestational and gestational diabetes mellitus (PGDM and GDM) on the development of fetal intracranial structures and spaces. METHODS: This prospective cross-sectional study involved singleton pregnancies between 20 and 32 weeks of gestation. The study comprised a control group (n = 65) of healthy pregnant women without diabetes mellitus (DM); a PGDM group (n = 43) of pregnant women having type 2 DM in a controlled diabetic state; and a GDM group (n = 26) of pregnant women with GDM diagnosed with 2-h 75-g oral glucose tolerance test and received intervention to reduce the diabetic impact on fetus. During neurosonographic evaluation, the simultaneous measurements of corpus callosum (CC) width and depth in the midsagittal image; and lateral craniocortical and posterior craniocortical widths of the subarachnoid space and insular and parieto-occipital fissure depths in the axial image were performed. Before statistical analysis, these values were carefully adjusted for the occipitofrontal diameter. RESULTS: The DM groups displayed substantially higher frequencies of family history of DM and obstetric history of GDM compared to the control group (p < 0.05). Regarding the neurosonographic parameters, the CC length and insular and parieto-occipital fissure depths were significantly increased in the GDM group but not in the PGDM group (p < 0.05). No significant difference was found among the study groups regarding other neurosonographic parameters (p > 0.05). CONCLUSION: The results of neurosonographical evaluation of fetal brain structures and spaces reveal that diabetic impact may not be seen in the presence of PGDM, especially in pregnant women receiving prenatal interventions to reduce or avoid diabetic adverse effects on fetal brain development. The effect of GDM on neurosonographically assessed fetal brain development should be evaluated in further studies with subjects matched for gestational weeks and antenatal care conditions.

Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies.

Congenital heart defects (CHDs) are the most common form of birth defects in humans. They occur in 9 out of 1000 live births and are defined as structural abnormalities of the heart. Understanding CHDs is difficult due to the heterogeneity of the disease and its multifactorial etiology. Advances in genomic sequencing have made it possible to identify the genetic factors involved in CHDs. However, genetic origins have only been found in a minority of CHD cases, suggesting the contribution of non-inherited (environmental) risk factors to the etiology of CHDs. Maternal pregestational diabetes is associated with a three- to five-fold increased risk of congenital cardiopathies, but the underlying molecular mechanisms are incompletely understood. According to current hypotheses, hyperglycemia is the main teratogenic agent in diabetic pregnancies. It is thought to induce cell damage, directly through genetic and epigenetic dysregulations and/or indirectly through production of reactive oxygen species (ROS). The purpose of this review is to summarize key findings on the molecular mechanisms altered in cardiac development during exposure to hyperglycemic conditions in utero. It also presents the various in vivo and in vitro techniques used to experimentally model pregestational diabetes. Finally, new approaches are suggested to broaden our understanding of the subject and develop new prevention strategies.

Preeclampsia and diabetes mellitus.

OBJECTIVE: The purpose of this paper is to provide a review of recent research on the relationship between preeclampsia and diabetes mellitus in pregnancy. METHODOLOGY: A structured search for literary sources in PubMed and ScienceDirect databases using keywords, followed by a selection of papers based on solid methodology. RESULTS: Preeclampsia is a serious condition, which complicates 2-7% of pregnancies. It causes maternal complications (organ dysfunction) and fetal complications (pathological haemodynamic parameters of the uteroplacental unit and fetal growth restriction). Pregnant women with pregestational diabetes have a 2- and 4-times higher risk of developing preeclampsia and the ones with gestational diabetes have 1.3-times higher risk. The main identified risk factors are inadequate compensation of diabetes, diabetic nephropathy, retinopathy and the duration of diabetes. To minimalize the risk of developing preeclampsia, a composite screening has been implemented. With a positive result a preventive use of acetylsalicylic acid from at the latest 16 and up until the 36th week is advised. Preeclampsia is also a risk factor for developing diabetes mellitus and other cardiovascular diseases later in life. For that reason, a long-term dispensary of women who had preeclampsia in pregnancy is recommended.

Area of the Fetal Ascending and Descending Aorta by Spatiotemporal Image Correlation in the Rendering Mode: Reproducibility and Comparison with Pregestational Diabetic Mothers.

Background: The objective of this study was to assess the ascending and descending aorta area measurements by three-dimensional (3D) ultrasound using spatiotemporal image correlation (STIC) in the rendering mode comparing these measurements with pregestational diabetic mothers and assessing the reproducibility of the method. Methods: We carried out a retrospective cross-sectional study with 58 normal and nine fetuses from pregestational diabetic mothers between 20 and 33 + 6 weeks of gestation. Fetal heart volumes were acquired at the level of four-chamber view to obtain the reconstructed planes for the ascending and descending aorta areas in the rendering mode. Linear regression was performed to assess the correlation between the fetal aorta areas and gestational age (GA). To assess the intra- and interobserver reproducibility, we used the concordance correlation coefficient (CCC). Results: The mean ascending and descending aorta areas were 0.12 (0.02-0.48) and 0.11 (0.04-0.39) cm2 in normal fetuses, respectively. There was a moderate positive correlation between GA and ascending aorta area measurements (0.005676*GA - 0.01283; r = 0.53, P < 0.0001) and strong positive correlation between GA and descending aorta area (0.01095*GA - 0.1581; r = 0.68, P < 0.0001). We observed a weak intra- and interobserver reproducibility with CCC ranging from 0.05 to 0.91. The mean difference in the ascending and descending aorta area measurements of normal and fetuses of pregestational diabetic mothers was -0.03 cm2 (P = 0.276) and -0.03 cm2 (P = 0.231), respectively. Conclusion: The fetal ascending and descending aorta area measurements obtained by 3D ultrasound using STIC in the rendering mode increased with GA in normal fetuses. The method showed weak intra- and interobserver reproducibility.

Association of change in haemoglobin A1c with adverse perinatal outcomes in women with pregestational diabetes.

AIMS: To determine whether a net decline in glycosylated haemoglobin (HbA1c ) from early to late pregnancy is associated with lower risk of adverse perinatal outcomes at delivery among women with pregestational diabetes. METHODS: A retrospective analysis from 2012 to 2016 at a tertiary care centre. The exposure was the net change in HbA1c from early (<20 weeks gestation) to late pregnancy (≥20 weeks gestation). Primary outcomes were large for gestational age (LGA) and neonatal hypoglycaemia. The association between outcomes per 6 mmol/mol (0.5%) absolute decrease in HbA1c was evaluated using modified Poisson regression, and adjusted for age, body mass index, White Class, early HbA1c and haemoglobin and gestational age at HbA1c measurement and delivery. RESULTS: Among 347 women with pregestational diabetes, HbA1c was assessed in early (9 weeks [IQR 7,13]) and late pregnancy (31 weeks [IQR 29,34]). Mean HbA1c decreased from early (59 mmol/mol [7.5%]) to late (47 mmol/mol [6.5%]) pregnancy. Each 6 mmol/mol (0.5%) absolute decrease in HbA1c was associated with a 12% reduced risk of LGA infant (30%, aRR:0.88; 95% CI:0.81,0.95), and a 7% reduced risk of neonatal hypoglycaemia (35%, aRR:0.93; 95% CI:0.87,0.99). Preterm birth (36%, aRR:0.93; 95% CI:0.89,0.98) and neonatal intensive care unit admission (55%, aRR:0.95; 95% CI:0.91,0.98) decreased with a net decline in HbA1c , but not caesarean delivery, pre-eclampsia, shoulder dystocia and respiratory distress syndrome. CONCLUSIONS: Women with pregestational diabetes with a reduction in HbA1c may have fewer infants born LGA or with neonatal hypoglycaemia. Repeated assessment of HbA1c may provide an additional measure of glycaemic control.