Metabolic changes in female rats exposed to intrauterine hyperglycemia and postweaning consumption of high-fat diet†.

We evaluated the influence of the hyperglycemic intrauterine environment and postweaning consumption of a high-fat diet (HFD) on the glycemia, insulin, lipid, and immunological profile of rat offspring in adulthood. Female rats received citrate buffer (Control-C) or Streptozotocin (a beta cell-cytotoxic drug to induce diabetes-D) on postnatal day 5. In adulthood, these rats were mated to obtain female offspring, who were fed a standard diet (SD) or HFD from weaning to adulthood (n = 10 rats/group). OC/SD and OC/HFD represent female offspring of control mothers and received SD or HFD, respectively; OD/SD and OD/HFD represent female offspring of diabetic mothers and received SD or HFD, respectively. At adulthood, the oral glucose tolerance test (OGTT) was performed and, next, the rats were anesthetized and euthanized. Pancreas was collected and analyzed, and adipose tissue was weighted. Blood samples were collected to determine biochemical and immunological profiles. The food intake was lower in HFD-fed rats and visceral fat weight was increased in the OD/HFD group. OC/HFD, OD/SD, and OD/HFD groups presented glucose intolerance and lower insulin secretion during OGTT. An impaired pancreatic beta-cell function was shown in the adult offspring of diabetic rats, regardless of diet. Interleukin (IL)-6 and IL-10 concentrations were lower in the OD/HFD group and associated to a low-grade inflammatory condition. The fetal programming was responsible for impaired beta cell function in experimental animals. The association of maternal diabetes and postweaning HFD are responsible for greater glucose intolerance, impaired insulin secretion and immunological change.

Evaluation of right side foetal myocardial performance index in pregestational and gestational diabetes mellitus.

The aim of our study is to investigate the myocardial performance index (MPI) of the right side of the foetal heart in pregestational and gestational diabetes mellitus and to compare it with non-diabetic pregnancies. This prospective cross-sectional study was conducted between August 2018 and March 2019 at Kanuni Sultan Suleyman Research and Training Hospital. Women with pregestational or gestational diabetes mellitus at 24-34 weeks of gestation were included in the study and non-diabetic pregnant women were included as the control group. MPI of the right side of the foetal heart were evaluated and compared between the groups. A total of 65 pregestational or gestational diabetic patients and 65 non-diabetic patients were included in the study. Isovolumetric contraction time and isovolumetric relaxation time values were significantly longer in the diabetic group (p < .001). Ejection time values were significantly shorter in the diabetic group (p < .001). MPI values were significantly higher in the diabetic group than the non-diabetic group (p < .001). In conclusion, MPI of the right side of the foetal heart is significantly higher in pregestational and gestational diabetes than in the non-diabetic group.IMPACT STATEMENTWhat is already known on this subject? Gestational diabetes mellitus causes foetal cardiomyopathy and foetal diastolic dysfunction. Myocardial performance index (MPI) is a non-invasive, Doppler-derived myocardial performance assessment that is independent of both heart rate and ventricular anatomy.What do the results of this study add? MPI of the right side of the foetal heart was significantly higher in pregestational and gestational diabetes than in the non-diabetic group. There was no difference in right ventricular MPI between pregestational and gestational groups in diabetic pregnancies, and between insulin using and not insulin using groups.What are the implications of these findings for clinical practice and/or further research? Our study results are promising. MPI of the right side of the foetal heart is significantly higher in pregestational and gestational diabetes than in the non-diabetic group. Prospective cohort studies evaluating serial MPI and evaluating by postpartum foetal echocardiography are needed to evaluate possible adverse effects of diabetes on foetal cardiac functions.

Elevated Anthropometric and Metabolic Indicators among Young Adult Offspring of Mothers with Pregestational Diabetes: Early Results from the Transgenerational Effect on Adult Morbidity Study (the TEAM Study).

Exposure to maternal diabetes in utero increases the risk in the offspring for a range of metabolic disturbances. However, the timing and variability of in utero hyperglycemic exposure necessary to cause impairment have not been elucidated. The TEAM Study was initiated to evaluate young adult offspring of mothers with pregestational diabetes mellitus. This paper outlines the unique enrollment challenges of the TEAM Study and preliminary analysis of the association between exposure to diabetes in pregnancy and adverse metabolic outcomes. The TEAM Study enrolls offspring of women who participated in a Diabetes in Pregnancy (DiP) Program Project Grant between 1978 and 1995. The DiP Study collected medical and obstetric data across pregnancy. The first 96 eligible offspring of women with pregestational diabetes were age-, sex-, and race-matched to adults from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 with an OGTT. Descriptive and regression analyses were employed to compare TEAM participants to NHANES participants. Among a subset of TEAM participants, we compared the metabolic outcomes across maternal glucose profiles using a longitudinal data clustering technique that characterizes level and variability, in maternal glucose across pregnancy. By comparing categories of BMI, TEAM Study participants had over 2.0 times the odds of being obese compared to matched NHANES participants (for class III obesity, OR = 2.81; 95% confidence interval (CI): 1.15, 6.87). Increasing levels of two-hour glucose were also associated with in utero exposure to pregestational diabetes in matched analyses. Exposure to pregestational diabetes in utero may be associated with an increased risk of metabolic impairment in the offspring with clinical implications.

Gestational diabetes mellitus - A metabolic and reproductive disorder.

Maternal health associated with Gestational Diabetes Mellitus (GDM) has been gaining significant research attention due to its severe risk and adverse health effects. GDM is the leading health disease in pregnant women. It is the most common metabolic disease and it can affect up to 25% of women during pregnancy. Pregnancy is a sensitive period that impacts both pregnant women and their unborn children's long-term health. It is a well-known fact that the leading causes of disease and mortality worldwide are diabetes mellitus and cancer, and specifically, women with diabetes mellitus are at a higher risk of developing breast cancer (BC). Women who have diabetes are equally vulnerable to reproductive diseases. Reproductive dysfunctions with diabetes are mainly attributed to coexisting polycystic ovarian syndrome (PCOS), obesity, and hyperinsulinemia, etc. Moreover, India has long been recognized as the world's diabetic capital, and it is widely acknowledged that particularly pregnant and lactating women are among the most affected by diabetes. In India, one-third (33%) of women with GDM had a history of maternal diabetes. Nevertheless, the latest research suggests that gestational diabetes is also a risk factor for cardiometabolic diseases of the mother and offspring. Therefore, in the 21st century, GDM imposes a major challenge for healthcare professionals. We intend to explore the role of diabetes on female reproductive function throughout various stages of life in the perspective of the changing prognosis, prevalence, and prevention of GDM.

Offspring birthweight and placental weight-does the type of maternal diabetes matter? A population-based study of 319 076 pregnancies.

INTRODUCTION: Our aim was to estimate the difference in birthweight and in placental weight in pregnancies with type 1 diabetes, type 2 diabetes, and gestational diabetes compared with pregnancies without diabetes. MATERIAL AND METHODS: By using data from the Medical Birth Registry of Norway during the years 2009-2017, we included 319 076 singleton pregnancies with delivery after the 21st week of pregnancy. We used linear regression analyses to estimate the difference in birthweight and in placental weight in grams (g) in pregnancies with type 1 diabetes, type 2 diabetes, and gestational diabetes, using pregnancies without diabetes as the reference. Adjustments were made for pregnancy duration and pre-pregnancy body mass index. RESULTS: In pregnancies without diabetes, mean crude birthweight was 3527 g (SD 552 g). The adjusted mean birthweight was 525 g (95% CI 502-548 g) higher in pregnancies with type 1 diabetes compared with pregnancies without diabetes. In pregnancies with type 2 diabetes, and pregnancies with gestational diabetes, birthweights were 192 g (95% CI 160-223 g) and 102 g (95% CI 93-110 g) higher, respectively. Mean crude placental weight was 664 g (SD 147 g) in pregnancies without diabetes. Compared with pregnancies without diabetes, the adjusted mean placental weight was 109 g (95% CI 101-116 g) higher in pregnancies with type 1 diabetes, 50 g (95% CI 39-60 g) higher in pregnancies with type 2 diabetes, and 31 g (95% CI 28-34 g) higher in pregnancies with gestational diabetes. CONCLUSIONS: The increase in birthweight and in placental weight associated with maternal diabetes was most pronounced for type 1 diabetes, followed by type 2 diabetes, and gestational diabetes.

Prescribing for pregnancy: managing diabetes.

Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.

Pregnancies in Diabetes and Obesity: The Capacity-Load Model of Placental Adaptation.

Excess nutritional supply to the growing fetus, resulting from maternal diabetes and obesity, is associated with increased risks of fetal maldevelopment and adverse metabolic conditions in postnatal life. The placenta, interposed between mother and fetus, serves as the gateway between the two circulations and is usually considered to mediate maternal exposures to the fetus through a direct supply line. In this Perspective, however, we argue that the placenta is not an innocent bystander and mounts responses to fetal "signals of distress" to sustain its own adequate function and protect the fetus. We describe several types of protection that the placenta can offer the fetus against maternal metabolic perturbations and offer a theoretical model of how the placenta responds to the intrauterine environment in maternal diabetes and obesity to stabilize the fetal environment. Our approach supports growing calls for early screening and control of pregnancy metabolism to minimize harmful fetal outcomes.

Use of the modified myocardial performance index for evaluating fetal cardiac functions in pregestational diabetic pregnancy babies.

The aim of this study is assessment of importance of use of the modified myocardial performance index (Mod-MPI) for the evaluation of foetal cardiac function in foetuses of women with pregestational diabetes mellitus (PDM). In this study, data of 30 pregnant patients aged 18-45 years diagnosed with PDM and 30 pregnant women aged 18-45 years with normal pregnancy and their babies were evaluated. Foetal echocardiographic and doppler measurements, foetal biometric measurements, umbilical artery and ductus venosus pulsatility indexes were measured in both PDM and control groups. The Mod-MPI was significantly higher in foetuses of PDM women. Many influences especially cardiac and postpartum complications are observed in infants of PDM women. The Mod-MPI is a simple and useful method for assessing foetal ventricular function. Our study has shown that PDM is associated with foetal ventricular dysfunction.Impact statementWhat is already known on this subject? Although MPI is frequently used in routine clinical assessment of neonates, it is not used adequately in foetuses. Many influences especially cardiac and postpartum complications are observed in infants of PDM women. However, there are few studies focussed specifically on the assessment of foetal cardiac function in PDM.What do the results of this study add? MPI, which shows both diastolic and systolic functions is independent of ventricular anatomy and foetal heart rate, was found significantly higher in diabetic mother foetuses, can be said to be a valuable parameter in evaluating foetal cardiac functions globally.What are the implications of these findings for clinical practice and/or further research? Our study has shown that foetuses PDM are associated with foetal ventricular dysfunction. For this MPI measurement can be routinely performed at foetal cardiac measurements in foetuses of PDM mothers.

Effect of maternal diabetes on fetal heart function on echocardiography: systematic review and meta-analysis.

OBJECTIVE: Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and meta-analysis aimed to estimate the effect of maternal diabetes on fetal cardiac function as measured by prenatal echocardiography. METHODS: We performed a search of the EMBASE, PubMed and The Cochrane Library databases, from inception to 4 July 2019, for studies evaluating fetal cardiac function using echocardiography in pregnancies affected by diabetes compared with uncomplicated pregnancies. Outcome measures were cardiac hypertrophy and diastolic, systolic and overall cardiac function as assessed by various ultrasound parameters. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data on interventricular septal (IVS) thickness, myocardial performance index (MPI) and E/A ratio were pooled for the meta-analysis using random-effects models. For pregnancies with diabetes, results were reported overall and according to whether diabetes was pregestational (PDM) or gestational (GDM). Results were also stratified according to the trimester in which fetal cardiac assessment was performed. RESULTS: Thirty-nine studies were included, comprising data for 2276 controls and 1925 women with pregnancy affected by diabetes mellitus (DM). Of these, 1120 had GDM, 671 had PDM and in 134 cases diabetes type was not specified. Fetal cardiac hypertrophy was more prevalent in diabetic pregnancies than in non-diabetic controls in 21/26 studies, and impaired diastolic function was observed in diabetic pregnancies in 22/28 studies. The association between DM and systolic function was inconsistent, with 10/25 studies reporting no difference between cases and controls, although more recent studies measuring cardiac deformation, i.e. strain, did show decreased systolic function in diabetic pregnancies. Of the studies measuring overall fetal cardiac function, the majority (14/21) found significant impairment in diabetic pregnancies. Results were similar when stratified according to GDM or PDM. These effects were already present in the first trimester, but were most profound in the third trimester. Meta-analysis of studies performed in the third trimester showed, compared with controls, increased IVS thickness in both PDM (mean difference, 0.75 mm (95% CI, 0.56-0.94 mm)) and GDM (mean difference, 0.65 mm (95% CI, 0.39-0.91 mm)) pregnancies, decreased E/A ratio in PDM pregnancies (mean difference, -0.09 (95% CI, -0.15 to -0.03)), no difference in E/A ratio in GDM pregnancies (mean difference, -0.01 (95% CI, -0.02 to 0.01)) and no difference in MPI in either PDM (mean difference, 0.04 (95% CI, -0.01 to 0.09)) or GDM (mean difference, 0.03 (95% CI, -0.01 to 0.06)) pregnancies. CONCLUSIONS: The findings of this review show that maternal diabetes is associated with fetal cardiac hypertrophy, diastolic dysfunction and overall impaired myocardial performance on prenatal ultrasound, irrespective of whether diabetes is pregestational or gestational. Further studies are needed to demonstrate the relationship with long-term outcomes. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cardiovascular hemodynamics in type 1 diabetic pregnancies at near-term gestation.

INTRODUCTION: Poor glycemic control in maternal type 1 diabetes mellitus during pregnancy can affect fetal cardiac and placental function. However, studies concerning fetal central hemodynamics have revealed conflicting results. We hypothesized that in pregnancies complicated by maternal type 1 diabetes, fetal cardiovascular and placental hemodynamics are comparable to the control fetuses at near-term gestation. In addition, we investigated the relation between newborn serum biomarkers of cardiac function and fetal cardiovascular and placental hemodynamics. Furthermore, we studied whether maternal diabetes is associated with placental inflammation. MATERIAL AND METHODS: In this prospective case-control study, fetal central and peripheral hemodynamics were assessed by ultrasonography in 33 women with type 1 diabetes and in 67 controls with singleton pregnancies between 34+2 and 40+2 gestational weeks. Newborn umbilical cord serum was collected to analyze cardiac natriuretic peptides (atrial and B-type natriuretic peptides) and troponin T concentrations. Placental tissue samples were obtained for cytokine analyses. RESULTS: Fetal ventricular wall thicknesses were greater and weight-adjusted stroke volumes and cardiac outputs were lower in the type 1 diabetes group than in the control group. Pulsatility in the aortic isthmus and inferior vena cava blood flow velocity waveforms was greater in the type 1 diabetes group fetuses than in the controls. A positive correlation was found between branch pulmonary artery and aortic isthmus pulsatility index values. Umbilical artery pulsatility indices were comparable between the groups. Umbilical cord serum natriuretic peptide and troponin T concentrations were elevated in the type 1 diabetes fetuses. These cardiac biomarkers correlated significantly with cardiovascular hemodynamics. Placental cytokine levels were not different between the groups. CONCLUSIONS: In maternal type 1 diabetes pregnancies, fetal cardiovascular hemodynamics is impaired. Maternal type 1 diabetes does not seem to alter placental vascular impedance or induce placental inflammation.

Fetal echocardiography at term in diabetic pregnancies helps predict the adverse neonatal outcome - Results of a prospective observational study from South India.

There is sparse Indian data on whether fetal echocardiography among pregnant diabetics would be useful to predict adverse perinatal/neonatal outcome. OBJECTIVES: To study fetal cardiac changes in diabetic mothers and non-diabetic controls from 24 weeks gestation until the neonatal period; correlate them with maternal glycemic control; study their implications on adverse perinatal/neonatal outcome. METHODOLOGY: Prospective observational cohort study. Pregnant diabetics (17 overt, 66 gestational) recruited beyond 24 weeks, divided as well (39) and poorly (44) controlled, based on American Diabetes Association 2016 criteria. Controls were 102 healthy non-diabetic pregnancies. Fetal echocardiography performed at weeks 24-32, 32-36, >37, and between 4 and 7 days on neonates. The thickness of Interventricular septum (IVS), Right Ventricle (RV), and Left ventricle (LV) assessed with M mode. E/A ratio across Tricuspid/Mitral valves and Tei index determined. TDI(Tissue Doppler imaging) used to assess tissue annular velocities across IVS, RV, and LV. Maternal glycemic control and various perinatal/neonatal adverse outcomes were recorded. RESULTS: Significant myocardial hypertrophy seen among fetuses of diabetic mothers versus controls, most severe at term among the poorly controlled diabetics. Structural changes persisted in the neonate. At term, fetal myocardial dysfunction was evident among diabetic pregnancies only as poor annular systolic velocity across IVS, RV using TDI. However, Tissue Doppler changes could not predict adverse perinatal/neonatal outcome. Myocardial dysfunction could not be demonstrated in the neonates. Myocardial hypertrophy at term was a surrogate marker for suboptimal glycemic control, and it could predict important neonatal morbidities like hypoglycaemia, hyperbilirubinemia, prolonged NICU stays, and persistent foetal cardiac shunts. CONCLUSION: Our study shows a significant association between fetal myocardial hypertrophy and maternal glycemic control among GDM pregnancies. There also seems to be an association between fetal myocardial hypertrophy and some of the adverse perinatal events including hypoglycemia. However these newborns were not found to have clinically relevant cardiac comorbidities even though there was significant septal hypertrophy in utero.

Awareness about diabetes and pregnancy among diabetes specialists and fellows: The YoSID diabetes and pregnancy project.

BACKGROUND AND AIMS: Despite evidence that pregnancy planning improves outcomes, in Italy, as in many other countries worldwide, <50% of women with diabetes prepare their pregnancy. The aim of this study was to document training and knowledge on diabetes and pregnancy (D&P) among diabetes professionals. METHODS AND RESULTS: We administered an anonymous online questionnaire, focused on diabetes and pregnancy planning, to diabetes team members. Between Nov-2017 and Jul-2018, n = 395 professionals (60% diabetes/endocrinology/internal medicine specialists, 28% fellows) completed the survey. Fifty-nine percent of the specialists, mainly (78%) those completing their fellowship after 2006, reported having received training on D&P during fellowship. Considering specialists reporting training, 43% correctly identified fetal risks of inadequate preconceptional glucose control and 55% maternal risks, 38% identified risks associated with overweight/obesity, and 39% would prescribe hormonal contraception to women with diabetes only if glucose control is good. CONCLUSIONS: The results of our survey suggest the need to improve training and awareness of professionals in the area of diabetes and pregnancy.

Bioinformatics enrichment analysis of genes and pathways related to maternal type 1 diabetes associated with adverse fetal outcomes.

Maternal type 1 diabetes mellitus (T1DM) may affect fetal development by altering the gene expression profile of the umbilical cord. The present study aimed to explore the T1DM-induced gene expression changes in the fetal umbilical cord. The raw gene expression profiles (ID: GSE51546) of umbilical cord tissue obtained from six normal mothers (non-diabetic) and six type 1 diabetic mothers were used to identify the differentially expressed genes. Genes that correspond to official gene symbols were selected for protein-protein interaction (PPI) and sub-network construction (combined score > 0.4). Functional annotation for Gene Ontology (GO) and pathway enrichment analysis were performed for genes involved in networking. A total of 110 differentially expressed genes were identified of which 38 were up-regulated while 72 were down-regulated. Only 37 genes were identified to significantly interact with each other. Hub genes including HSPA4, KCTD6, UBE2G1, FBXL19, and EHMT1 were up-regulated while KBTBD7, TRIM32, and NUP were down-regulated. T1DM had a major effect on the expression of genes involved in cellular death and differentiation, cell signaling and communication, protein modification and regulation of GTPase activity. Total 27 pathways were enriched and genes related to Wnt signaling, VEGF signaling, inflammation mediated by chemokine and cytokine signaling pathways, FGF signaling pathways and GnRH receptor pathways were found significantly affected by T1DM. Our results suggest that the T1DM environment seems to alter umbilical cord gene expression involved in the regulation of pathophysiology of the diabetic mother which in turn may lead to long-term consequences in various tissues in infants. This study provides insight into the molecular mechanism underlying the adverse pregnancy outcomes of maternal T1DM.

Adverse maternal and neonatal outcomes in pregnant women with abnormal glucose metabolism.

AIMS: To assess the prevalence and risk of adverse perinatal outcomes in pregnant women with abnormal glucose metabolism. METHODS: 3269 Chinese pregnant women with singleton delivery were studied, including 787 diagnosed as gestational diabetes mellitus (GDM), 115 pregnancy with diabetes (PWD), and 2367 normal glucose tolerance (NGT). The prevalence and risk of adverse maternal and fetal outcomes were compared and assessed among the three groups, and the related risk factors of the glucose metabolism for adverse pregnancy outcomes were evaluated by binary logistic regression. RESULTS: Compared to NGT, maternal GDM and PWD faced increased risk of adverse perinatal outcomes such as pregnancy-induced hypertension (odds ratio (OR) 1.78 [95% confidence interval (CI): 1.17-2.72]; 4.31 [95% CI: 2.32-7.98]), low birth weight (OR 1.51 [95% CI: 1.01-2.28]; 4.05 [95% CI: 2.17-7.55]). And PWD group exhibited remarkably higher risk for preterm delivery (OR 2.88 [95% CI: 1.68-4.94]) and stillbirth (OR 7.78 [95% CI: 2.44-24.84]) than other two groups. The increased fasting insulin and glycated hemoglobin A1c were successively independent risk factors for maternal and neonatal adverse outcomes. CONCLUSIONS: Gestational abnormal glucose metabolism is associated with the remarkably increased risk of adverse perinatal outcomes, and PWD has higher risk of adverse perinatal outcomes than GDM.

Prior breastfeeding experience and infant feeding at discharge among women with pregestational diabetes mellitus.

OBJECTIVE: To compare multiparous women with pregestational diabetes mellitus (PGDM) with and without prior breastfeeding (BF) experience and to ascertain their infants' feeding type during hospitalization and at discharge. METHODS: A retrospective cohort study of 304 women with PGDM who delivered at ≥34 weeks gestational age (GA). Prior BF experience and infant feeding preference was declared prenatally. At discharge, BF was defined as exclusive or partial. RESULTS: BF experience and no experience groups were similar in diabetes type 1 and 2, race and number of pregnancies. Women with no experience had more spontaneous abortions (35 vs 27%), fewer term deliveries (51 vs 61%) and living children (median 1 vs 2). In the current pregnancy, mode of delivery: vaginal (36 & 37%), cesarean (64 & 63%), birthweight (3592 & 3515 g), GA (38 & 37 w), NICU admission (14 & 11%) and hypoglycemia (44 & 43%) were similar. Women with experience intended to BF (79 vs 46%), their infants' first feeding was BF (64 vs 36%) and had lactation consults (96 vs 63%) more often than those without experience. At discharge, women with BF experience were different in rate of exclusive BF (33 vs 11%), partial BF (48 vs 25%) and formula feeding (19 vs 64%). CONCLUSION: Prior BF experience leads to better BF initiation rates while the absence of BF experience adds a risk for BF initiation failure. A detailed BF history could provide insight into obstacles that lead to unsuccessful BF experiences and may help define appropriate preventive or corrective strategies.

Associations of Different Types of Maternal Diabetes and Body Mass Index With Offspring Psychiatric Disorders.

Importance: Maternal obesity, pregestational type 1 and 2 diabetes, and gestational diabetes have been reported to increase the risk of autism spectrum disorder and attention-deficit/hyperactivity disorder in the mothers' offspring. However, the associations of maternal diabetes disorders and body mass index jointly with psychiatric disorders among offspring are less well documented, especially for type 2 diabetes. Objective: To examine the associations of different types of maternal diabetes, separately and together with maternal obesity, with psychiatric disorders in the mothers' offspring. Design, Setting, and Participants: This population-based cohort study used data from nationwide registries in Finland encompassing all 649 043 live births occurring between 2004 and 2014. The study and data analysis were conducted from January 1, 2019, to July 5, 2019. Exposures: Maternal prepregnancy body mass index, insulin-treated pregestational diabetes, and pregestational type 2 diabetes and gestational diabetes without insulin treatment. Main Outcomes and Measures: Psychiatric diagnoses and prescription of psychotropic drugs among the mothers' offspring. Cox proportional hazards models were adjusted for birth year, sex, mode of delivery, maternal age, number of fetuses, parity, mother's country of birth, mother's marital status, maternal smoking, maternal psychiatric disorder, and maternal systemic inflammatory disease. Results: The mean (SD) age of mothers was 30.20 (5.37) years; 357 238 of 394 302 mothers (90.6%) were born in Finland. Of the 647 099 births studied, 4000 fetuses (0.62%) were exposed to maternal insulin-treated pregestational diabetes, 3724 (0.57%) were exposed to type 2 diabetes, and 98 242 (15.18%) were exposed to gestational diabetes; 34 892 offspring (5.39%) later received a diagnosis of a mild neurodevelopmental or psychiatric disorder. Non-insulin-treated type 2 diabetes in severely obese mothers, compared with normal-weight mothers without diabetes, was associated with psychiatric disorders in the offspring (hazard ratio, 1.97; 95% CI, 1.64-2.37), although with a lower effect size than that for severely obese mothers with insulin-treated pregestational diabetes (hazard ratio, 2.71; 95% CI, 2.03-3.61). The largest effect sizes were found for mood disorders, attention-deficit/hyperactivity disorder and conduct disorders, and autism. Gestational diabetes in severely obese mothers had a lower overall effect size (hazard ratio, 1.61; 95% CI, 1.50-1.72). Diabetes in normal-weight mothers was not associated with psychopathologic disorders in the offspring. Conclusions and Relevance: Severe obesity in mothers with diabetes was associated with an increased overall risk for psychiatric disorders in their offspring. The risk was highest for those exposed to insulin-treated pregestational diabetes, followed by non-insulin-treated type 2 diabetes and gestational diabetes. These findings may have implications for managing pregnancies.

Exercise in Pregnant Women with Diabetes.

PURPOSE OF REVIEW: Diabetes affects an increasing number of pregnancies. Regular exercise is recommended for pregnant women without diabetes, but whether exercise during pregnancy also benefits women with gestational diabetes (GDM) or preexisting (type 1 or type 2) diabetes or if these women have any specific risks is unclear. RECENT FINDINGS: Recent evidence suggests that low- to moderate-intensity exercise improves blood glucose and may delay insulin initiation for women with GDM. Exercise is also safe, with no reports of increased maternal or neonatal complications. Few studies evaluated exercise as adjunct therapy for pregnant women with preexisting diabetes, precluding a thorough assessment in this population. Low- to moderate-intensity exercise during pregnancy safely improves glycemic control among women with GDM. More studies are needed to evaluate the impact of exercise in pregnant women with preexisting diabetes. Whether a specific type, volume, or timing of activity is most effective is not known.

Maternal factors, ultrasound and placental function parameters in early pregnancy as predictors of birth weight in low-risk populations and among patients with pre-gestational diabetes.

OBJECTIVES: The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. During the first trimester consultation, all patients were surveyed and the following data were collected: age, BMI, reproductive history, comorbidities and smoking. We also collected blood samples and assessed PlGF, PAPP-A, and BhCG levels. RESULTS: Our study showed that newborn birth weight negatively correlated with mother's age, her diastolic blood pressure, PI of her uterine arteries and BhCG protein levels. Moreover, birth weight directly correlated with PlGF and PAPPA-A protein levels, and maternal early-pregnancy BMI. CONCLUSIONS: LGA diagnosis in the first trimester of pregnancy allows for selection and modification of some risk factors and closer monitoring of endangered fetuses throughout the pregnancy, with emphasis on the perinatal period. Parameters with confirmed usefulness in the prediction of birth weight in the first trimester included: maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI.