Maternal Pregestational Diabetes Mellitus Research Articles

Clinical and radiological evaluation of caudal regression syndrome.

Caudal regression syndrome is a form of segmental spinal dysgenesis involving the caudal spinal column, ranging from segmental coccygeal agenesis to extensive thoracolumbar agenesis with varying degrees of spinal cord dysgenesis. A majority of caudal regression cases are sporadic but maternal pre-gestational diabetes mellitus is an important risk factor. Imaging is an integral part of management of caudal regression syndrome. Antenatal diagnosis on obstetric ultrasound and evaluation with fetal MRI is ideal. Early postnatal diagnosis and/or detailed evaluation with MRI is essential for early management to improve outcomes. Pang classification categorizes caudal regression syndrome into two categories based on the position of the conus while Renshaw classification is based on the degree of vertebral column agenesis. Caudal regression syndrome may be associated with several additional anomalies, both spinal and extraspinal. A number of genitourinary and gastrointestinal anomalies have been described in association with caudal regression syndrome. The field of view of MRI of the lumbosacral spine in caudal regression syndrome needs to be extended to visualize the retroperitoneal structures without the use of a saturation band. Syndromic associations may be suspected, and additional imaging performed, based on findings of extended field of view MRI of the spine. Associated sacral masses and filar abnormalities need to be identified and may also require surgical treatment. The multisystem nature of this disease necessitates a multimodality approach to the evaluation and management of caudal regression syndrome with close cooperation between pediatric neuroradiologists and body radiologists as well as multiple clinical teams. Appropriate early management with surgical correction as necessary can significantly improve prognosis and survival in caudal regression syndrome.

Caudal regression syndrome type 1 with minimally invasive computed tomography and magnetic resonance imaging autopsy: a case report

BackgroundCaudal regression syndrome is a rare complex congenital anomaly with reduced penetrance and phenotypic variability characterized by osseous defects of the caudal spine, lower limb anomalies, and accompanying genitourinary, gastrointestinal/anorectal, and cardiac system soft tissue defects. We report a rare presentation of type 1 caudal regression syndrome in a pregnant woman with preexisting diabetes, in which early recognition of severe fetal anomalies on routine antenatal ultrasound facilitated confirmation with fetal magnetic resonance imaging to characterize extent of disease and prognosticate fetal outcome.Case presentationThis case of type 1 caudal regression syndrome in the setting of maternal pregestational diabetes mellitus resulted in stillbirth. The mother was a 29-year-old Caucasian primigravida female with past medical history of poorly controlled type 2 diabetes managed with metformin prior to pregnancy, prompting admission for glucose management and initiation of insulin at 13 weeks. Baseline hemoglobin A1c was high at 8.0%. Fetal ultrasound at 22 weeks was notable for severe sacral agenesis, bilateral renal pelvis dilatation, single umbilical artery, and pulmonary hypoplasia. Fetal magnetic resonance imaging at 29 weeks showed absent lower two-thirds of the spine with corresponding spinal cord abnormality compatible with type 1 caudal regression syndrome. The mother delivered a male stillborn at 39 and 3/7 weeks. Minimally invasive postmortem magnetic resonance imaging and computed tomography autopsy were performed to confirm clinical findings when family declined conventional autopsy. Etiology of sacral agenesis was attributed to poorly controlled maternal diabetes early in gestation.ConclusionMaternal preexisting diabetes is a known risk factor for development of congenital malformations. This rare case of type 1 caudal regression syndrome in a mother with preexisting diabetes with elevated hemoglobin A1c highlights the importance of preconception glycemic control in diabetic women and the utility of fetal magnetic resonance imaging for confirmation of ultrasound findings to permit accurate prognostication. Additionally, minimally invasive postmortem magnetic resonance imaging and computed tomography autopsy can facilitate diagnostic confirmation of clinical findings in perinatal death due to complex congenital anomalies while limiting the emotional burden on bereaved family members who decline conventional autopsy.

The Association of Nutrition and Exercise Behaviors of Women with Diabetes in Pregnancy with Infant Breastfeeding Practices.

Background: Although breastfeeding confers significant benefits to infants, women with diabetes in pregnancy experience unique nutrition and health challenges, which may influence infant feeding practice. This study aimed to determine the association between nutrition and exercise behaviors of women with diabetes in pregnancy and breastfeeding at birth and 6 months. Methods: A secondary data analysis of a longitudinal study on maternal pregestational diabetes mellitus (DM) and gestational diabetes (GDM) and infant development was conducted. Women self-reported engaging in nutrition behaviors, such as using meal plans, and exercise health behaviors. Primary outcomes were exclusive breastfeeding at birth and any breastfeeding at 6 months. Logistic regression models adjusted for significant maternal-infant covariates. Results: Of n = 48 women with diabetes in pregnancy, 94% had GDM and 6% had pregestational type 1 or type 2 DM. Forty percent of women exclusively breastfed at birth and 68% partially or exclusively breastfed at 6 months (of n = 34 with complete 6-month data). Women who cooked their own meals had two times greater adjusted odds of exclusive breastfeeding at birth (adjusted odds ratio [AOR] = 1.94, 95% confidence interval [CI] = 1.12-5.11), and women who exercised during pregnancy had seven times greater adjusted odds of any breastfeeding at 6 months (AOR = 7.2, 95% CI = 1.10-42.8). Conclusion: Nutrition and exercise behaviors were associated with exclusive breastfeeding at birth and any breastfeeding at 6 months. Health behaviors to effectively manage diabetes during pregnancy may inform efforts to improve breastfeeding initiation and duration, and future studies in a larger sample are needed.

Abstract P1002: Impact Of Maternal Diabetes-associated Oxidative Stress On The Developing Endocardium

Congenital heart defects (CHD) affect 1% of all live births and are the leading cause of birth defect-related mortality. The etiology of CHD is multifactorial as genomic variation and environmental factors act as contributors. Among the environmental teratogens, maternal pre-gestational diabetes mellitus and its concurrent maternal hyperglycemia (matHG) is associated with a ~5-fold increased risk of CHD. Oxidative stress (Ox-Stress) due to generation of excess reactive oxygen species is observed in embryonic hearts exposed to matHG in animal models, but its teratogenic effect on cardiac development is not understood. Additionally, we observed murine embryonic hearts exposed to matHG have reduced expression of Notch1, which is highly expressed in endocardial cells (EC) and reported a gene-environment interaction between matHG and Notch1 haploinsufficiency that results in CHD in mice. We hypothesize that matHG-induced Ox-Stress leads to the downregulation of endocardial Notch signaling and aberrant EC function leading to CHD. To investigate the effects of matHG-induced Ox-Stress on endocardial Notch signaling, we examined mouse embryos exposed to matHG with conditional deletion of Notch1 in EC. We used lineage tracing to detect differences in EC-derived structures in hyperglycemia and normoglycemia-exposed embryonic hearts. Finally, we asked whether modulating intracellular levels of Ox-Stress can rescue the CHD phenotypes observed with matHG exposure by generating mouse embryos with overexpression of the antioxidant gene, SOD1 . Results show conditional deletion of endocardial Notch1 in embryos exposed to matHG leads to highly penetrant CHD. We found increased Ox-Stress and reduced number of EC-derived mesenchymal cells in endocardial cushions of mouse hearts exposed to matHG. Finally, embryos with SOD1 overexpression have reduced Ox-Stress and decreased incidence of CHD compared to non-SOD1 overexpressing littermates. This works shows that matHG-induced Ox-Stress may be associated with aberrant EC and EC-derived cell function via disruption of Notch signaling. Mitigating Ox-Stress during cardiac development may lead to rescue of Notch signaling and EC function to reduce CHD incidence from matHG exposure.

Association between masked hypertension and late-onset fetal growth restriction at advanced maternal age

Fetal growth restriction (FGR) is a major risk factor for complicated pregnancy including stillbirth. The all-pathophysiology results in uteroplacental insufficiency. Hypertension chronic or pregnancy-related complicates the all-prenatal periods. The relationship between fetal growth restriction and hypertension is well-known and this risk increases with maternal age. Late-onset FGR is diagnosed >32 weeks. Masked hypertension (MH) is a phenotype of hypertension when clinic blood pressure is in the normal range in the office but elevated outside the office. This study examined the risk of late-onset FGR and masked hypertension at advanced maternal age. Sixty pregnant women over 40 years old were included in the study who delivered at our hospital with late-onset fetal growth restriction diagnosis. After taking detailed anamnesis from all individuals included in the study, detailed physical examination, obstetric examination and ambulatory blood pressure monitoring (ABPM) were performed. Women with maternal chronic hypertension, pregestational or gestational diabetes mellitus, chronic kidney disease, rheumatoid disease history, tobacco use, cardiac arrhythmia, fetal genetic abnormality or placental abnormality were excluded from the study. The prevalence of masked hypertension was statistically significantly higher in the group with late intrauterine growth. (n:13, 43% vs n:5, 16.7% p=0.02). Office systolic BP (125.5±4.1 mmHg vs 118.5±5.7 mmHg p=0.016), 24-hour systolic BP measurement (125±9 mmHg vs 119.7±5.7 mmHg p=0.03), and ambulatory nocturnal diastolic BP measurement (66.7±10 mmHg vs. 61.±5.5 mmHg p=0.03) was higher in the group with late FGR. Hypertension can lead to complications in the perinatal period. There is a bad association between FGR and hypertension. Masked hypertension should be considered especially in advanced age pregnant individuals with FGR.

Hyperglycemia affects neuronal differentiation and Nestin, FOXO1, and LMO3 mRNA expression of human Wharton's jelly mesenchymal stem cells of children from diabetic mothers

Pregestational Diabetes Mellitus (PDM) during pregnancy constitutes an unfavorable embryonic and fetal development environment, with a high incidence of congenital malformations (CM). Neural tube defects are the second most common type of CM in children of diabetic mothers (CDM), who also have an elevated risk of developing neurodevelopmental disorders. The mechanisms that lead to these neuronal disorders in CDM are not yet fully understood. The present study aimed to know the effect of hyperglycemia on proliferation, neuronal differentiation percentage, and expression of neuronal differentiation mRNA markers in human umbilical cord Wharton's jelly mesenchymal stem cells (hUCWJMSC) of children from normoglycemic pregnancies (NGP) and PDM. We isolated and characterized hUCWJMSC by flow cytometry, immunofluorescence, RT-PCR and were induced to differentiate into adipocytes, osteocytes, and neurons. Proliferation assays were performed to determine the doubling time, and Nestin, TUBB3, FOXO1, KCNK2, LMO3, and MAP2 mRNA gene expression was assessed by semiquantitative RT-PCR. Hyperglycemia significantly decreased proliferation and neuronal differentiation percentage in NGP and PDM cells treated with 40 mM d-glucose. Nestin mRNA expression decreased under control glycemic conditions, while FOXO1, KCNK2, LMO3, and MAP2 mRNA expression increased during neuronal differentiation in both NGP and PDM cells. On the other hand, under hyperglycemic conditions, Nestin was significantly decreased in cells from NGP but not in cells from PDM, while mRNA expression of FOXO1 and LMO3 was significantly increased in cells from NGP, but not in cells from PDM. We found evidence that maternal PDM, with hyperglycemia in culture, affects the biological properties of fetal cells. All these results could be part of fetal programming.

Effect of maternal pregestational diabetes mellitus on congenital heart diseases.

The increasing population of diabetes mellitus in adolescent girls and women of childbearing age contributes to a large number of pregnancies with maternal pregestational diabetes mellitus. Congenital heart diseases are a common adverse outcome in mothers with pregestational diabetes mellitus. However, there is little systematic information between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring. Literature selection was performed in PubMed. One hundred and seven papers were cited in our review, including 36 clinical studies, 26 experimental studies, 31 reviews, eight meta-analysis articles, and six of other types. Maternal pregestational diabetes mellitus poses a high risk of congenital heart diseases in the offspring and causes variety of phenotypes of congenital heart diseases. Factors such as persistent maternal hyperglycemia, oxidative stress, polymorphism of uncoupling protein 2, polymorphism of adiponectin gene, Notch 1 pathway, Nkx2.5 disorders, dysregulation of the hypoxia-inducible factor 1, and viral etiologies are associated with the occurrence of congenital heart diseases in the offspring of mothers with pregestational diabetes mellitus. Treatment options including blood sugar-reducing, anti-oxidative stress drug supplements and exercise can help to prevent maternal pregestational diabetes mellitus from inducing congenital heart diseases. Our review contributes to a better understanding of the association between maternal pregestational diabetes mellitus and congenital heart diseases in the offspring and to a profound thought of the mechanism, preventive and therapeutic measurements of congenital heart diseases caused by maternal pregestational diabetes mellitus.

Early-life determinants of childhood plasma insulin levels: implications for primordial prevention of diabetes.

We earlier reported prematurity as an independent risk factor for elevated insulin levels. Investigation is still lacking on the influence of prenatal and perinatal factors on childhood insulin levels. In this secondary analysis of a prospective birth cohort, plasma insulin levels were measured at birth and early childhood. Regression models identified early-life factors associated with the primary outcome: log-transformed childhood plasma insulin levels. One thousand one hundred and nine children had insulin levels at birth and 825 at both time points. Compared to term, preterm infants had higher plasma insulin levels (geometric mean) at birth (612, 95% CI 552-679 vs. 372, 95% CI 345-402 pmol/ml) and in early childhood (547, 95% CI 494-605 vs. 445, 95% CI 417-475 pmol/ml). Factors associated with higher early childhood insulin levels included higher insulin level at birth, black race, female sex, maternal smoking during pregnancy, maternal perceived stress, in utero drug exposure, maternal pregestational diabetes mellitus, and maternal preconception overweight and obesity. In this high-risk US birth cohort, we identified multiple prenatal and perinatal risk factors for higher early childhood insulin levels, in addition to prematurity. These findings lend support to primordial preventive strategies for diabetes mellitus. In this secondary analysis of a large prospective study from a high-risk racially diverse cohort, we identify biological and social factors that contribute to elevated levels of plasma insulin in early childhood. Our study also investigates factors affecting plasma insulin in preterm infants along with comorbidities commonly seen during the neonatal intensive care stay. Our work reaffirms the importance of Developmental Origins of Health and Disease with regards to in utero programming of insulin levels. Our work supports the possibility that primordial preventive strategies for diabetes mellitus in high-risk populations may need to begin as early as the prenatal period.

Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births.

Pre-gestational diabetes mellitus (PGDM) has been known to be a risk factor for congenital heart defects (CHDs) for decades. However, the associations between maternal PGDM and gestational diabetes mellitus (GDM) and the risk of specific types of CHDs and congenital anomalies (CAs) in other systems remain under debate. We aimed to investigate type-specific CAs in offspring of women with diabetes and to examine the extent to which types of maternal diabetes are associated with increased risk of CAs in offspring. We searched PubMed and Embase from database inception to 15 October 2021 for population-based studies reporting on type-specific CAs in offspring born to women with PGDM (combined type 1 and 2) or GDM, with no limitation on language. Reviewers extracted data for relevant outcomes and performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. This study was registered in PROSPERO (CRD42021229217). Primary outcomes were overall CAs and CHDs. Secondary outcomes were type-specific CAs. Overall, 59 population-based studies published from 1990 to 2021 with 80,437,056 participants met the inclusion criteria. Of the participants, 2,407,862 (3.0%) women had PGDM and 2,353,205 (2.9%) women had GDM. The meta-analyses showed increased risks of overall CAs/CHDs in offspring born to women with PGDM (for overall CAs, relative risk [RR] = 1.99, 95% CI 1.82 to 2.17, P < 0.001; for CHDs, RR = 3.46, 95% CI 2.77 to 4.32, P < 0.001) or GDM (for overall CAs, RR = 1.18, 95% CI 1.13 to 1.23, P < 0.001; for CHDs, RR = 1.50, 95% CI 1.38 to 1.64, P < 0.001). The results of the meta-regression analyses showed significant differences in RRs of CAs/CHDs in PGDM versus GDM (all P < 0.001). Of the 23 CA categories, excluding CHD-related categories, in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories; the corresponding RRs ranged from 1.57 (for hypospadias, 95% CI 1.22 to 2.02) to 18.18 (for holoprosencephaly, 95% CI 4.03 to 82.06). Maternal GDM was associated with a small but significant increase in the risk of CAs in 9 categories; the corresponding RRs ranged from 1.14 (for limb reduction, 95% CI 1.06 to 1.23) to 5.70 (for heterotaxia, 95% CI 1.09 to 29.92). The main limitation of our analysis is that some high significant heterogeneity still persisted in both subgroup and sensitivity analyses. In this study, we observed an increased rate of CAs in offspring of women with diabetes and noted the differences for PGDM versus GDM. The RRs of overall CAs and CHDs in offspring of women with PGDM were higher than those in offspring of women with GDM. Screening for diabetes in pregnant women may enable better glycemic control, and may enable identification of offspring at risk for CAs.

Pre-gestational diabetes: Maternal body mass index and gestational weight gain are associated with augmented umbilical venous flow, fetal liver perfusion, and thus birthweight.

To assess how maternal body mass index and gestational weight gain are related to on fetal venous liver flow and birthweight in pregnancies with pre-gestational diabetes mellitus. In a longitudinal observational study, 49 women with pre-gestational diabetes mellitus were included for monthly assessments (gestational weeks 24-36). According to the Institute Of Medicine criteria, body mass index was categorized to underweight, normal, overweight, and obese, while gestational weight gain was classified as insufficient, appropriate or excessive. Fetal size, portal flow, umbilical venous flow and distribution to the fetal liver or ductus venosus were determined using ultrasound techniques. The impact of fetal venous liver perfusion on birthweight and how body mass index and gestational weight gain modified this effect, was compared with a reference population (n = 160). The positive association between umbilical flow to liver and birthweight was more pronounced in pregnancies with pre-gestational diabetes mellitus than in the reference population. Overweight and excessive gestational weight gain were associated with higher birthweights in women with pre-gestational diabetes mellitus, but not in the reference population. Fetuses of overweight women with pre-gestational diabetes mellitus had higher umbilical (p = 0.02) and total venous liver flows (p = 0.02), and a lower portal flow fraction (p = 0.04) than in the reference population. In pre-gestational diabetes mellitus pregnancies with excessive gestational weight gain, the umbilical flow to liver was higher than in those with appropriate weight gain (p = 0.02). The results support the hypothesis that umbilical flow to the fetal liver is a key determinant for fetal growth and birthweight modifiable by maternal factors. Maternal pre-gestational diabetes mellitus seems to augment this influence as shown with body mass index and gestational weight gain.

Maternal diabetes-related malformations in Utah: A population study of birth prevalence 2001-2016.

Maternal pregestational diabetes mellitus is associated with an increased risk for congenital malformations of about 2-4 times the background risk. Notably, the types and patterns of congenital malformations associated with maternal diabetes are nonrandom, with a well-established increased risk for specific classes of malformations, especially of the heart, central nervous system, and skeleton. While the increased risk in clinical and epidemiological studies is well documented in the literature, a precise estimate of overall birth prevalence of these specific congenital malformations among women with maternal pregestational diabetes, is lacking. The purpose of this study was to determine total prevalence of structural malformations associated with maternal pregestational diabetes mellitus in a population-based study. We identified infants with specific birth defects whose mother had pregestational diabetes mellitus in the Utah Birth Defect Network (UBDN), an active birth defects surveillance program that registers the occurrence of selected structural defects in the state of Utah. We defined specific maternal diabetes-related malformations based on epidemiologic and clinical studies in the literature. Of the 825,138 recorded Utah births between 2001 and 2016, a total of 91 cases were identified as likely having diabetic embryopathy within UBDN data. The prevalence of diabetes-related congenital malformation cases was calculated per year; the overall prevalence of diabetes-related malformations 2001-2016 was 1.1 per 10,000 births in Utah (95% CI, 0.9-1.3). Knowledge of the overall prevalence of diabetes-related malformations is important in predicting the number of cases that are potentially prevented with the implementation of programs to foster preconceptional management of maternal pregestational diabetes.

Association between maternal pregestational diabetes mellitus and spina bifida: A population-based case-control study, Finland, 2000-2014.

Maternal pregestational diabetes mellitus (PGDM) is a known risk factor for neural tube defects. We examined the association between maternal PGDM and spina bifida in the offspring using PGDM status from medical records in Finland. We conducted a nationally representative, multiregistry, population-based case-control study in Finland. Cases were included if they were live or stillborn infants and diagnosed with spina bifida and delivered between years 2000 and 2014 in Finland. Controls were Finnish infants without spina bifida or other major structural birth defects and delivered during the same time period as cases. Clinical and demographic data were obtained by linking multiple national health registers and census. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CI) for PGDM were estimated using logistic regression analysis. Interaction by maternal obesity was examined. Our study included 181 spina bifida cases (61% isolated) and 876,672 controls. Overall, 2.2% percent of all case, and 0.5% of control mothers, had PGDM during pregnancy. Maternal PGDM was significantly associated with an increased odds of spina bifida (adjusted OR 4.35; 95% CI 1.37, 13.82). A similar association was found in our subanalysis on isolated spina bifida cases (adjusted OR 4.41; 95% CI 1.07, 18.24). There was no significant interaction by maternal obesity. Maternal PGDM was positively associated with spina bifida in Finland, and maternal obesity did not modify this effect. We lacked information on maternal PGDM for electively terminated and spontaneously aborted cases; results should be interpreted with caution.

Applicability of Standardized Early Fetal Heart Examination in the Obese Population.

This study aimed to evaluate the impact of obesity on early evaluation of fetal cardiac landmarks using a standardized examination method at the time of nuchal translucency scan. This was a cross-sectional study of an ongoing prospective cohort at high risk for congenital heart defects. We used a standardized examination protocol using 2-dimensional sonography with power Doppler in the evaluation of fetal cardiac landmarks consisting of 4-chamber view, outflow tract relationship, and transverse arches view. The study population was stratified based on maternal body mass index into nonobese (<30 kg/m2 ) and obese (≥30 kg/m2 ). Groups were compared in terms of satisfactory evaluation of fetal cardiac landmarks, transvaginal sonography use, and scan times required for the evaluations. Subanalysis was performed by further categorizing obesity into nonmorbid obesity (30.0-39.9 kg/m2 ) and morbid obesity (≥40 kg/m2 ). A total of 190 patients were evaluated. Of these, 48.4% (n = 92) were obese. The most common indication for fetal cardiac assessment was maternal pregestational diabetes mellitus (42.6%). Transvaginal sonography was utilized in one nonobese woman (1.4%) and 11 obese women (12%) (P = .002). The satisfactory evaluation of 4-chamber view, outflow tract relationship, transverse arches view, and all views were not significantly different between groups (P > .05). The scan time was about 5 minutes longer in the obese group compared with nonobese group (P = .020). Obesity does not hamper early evaluation of fetal cardiac landmarks around the time of nuchal translucency scan. However, obese patients are more likely to require transvaginal examinations.

The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity and Diabetes.

Prenatal exposure to metabolic disturbances is associated with increased risk of offspring neurodevelopmental impairment and autism spectrum disorder, while little is known about the joint effect of maternal obesity and diabetes. With this study, we aim to assess the joint effect of maternal obesity and diabetes on the risk for offspring psychiatric and mild neurodevelopmental disorders. Nationwide registries were used to link data of all live births in Finland between 2004 and 2014 (n = 649 043). Cox proportional hazards modeling adjusting for potential confounders was applied to estimate the effect of maternal obesity, pregestational diabetes mellitus (PGDM), and gestational diabetes mellitus, as well as their joint effects, on the outcomes of offspring psychiatric and mild neurodevelopmental diagnoses and offspring prescription of psychotropic drugs. Among mothers without diabetes, severely obese mothers had 67% to 88% increased risk of having a child with mild neurodevelopmental disorders (hazard risk ratio [HR] = 1.69; 95% confidence interval [CI] = 1.54-1.86), attention-deficit/hyperactivity disorder or conduct disorder (HR = 1.88; 95% CI = 1.58-2.23), and psychotic, mood, and stress-related disorders (HR = 1.67; 95% CI = 1.31-2.13) compared with mothers with a normal BMI. PGDM implied a further risk increase for all groups of psychiatric diagnoses with onset in childhood or adolescence in mothers with severe obesity. Marked effects were found particularly for autism spectrum disorder (HR = 6.49; 95% CI = 3.08-13.69), attention-deficit/hyperactivity disorder and conduct disorder (HR = 6.03; 95% CI = 3.23-11.24), and mixed disorders of conduct and emotions (HR = 4.29; 95% CI = 2.14-8.60). Gestational diabetes mellitus did not increase the risk highly for these offspring disorders. Maternal PGDM combined with severe maternal obesity markedly increases the risk of several children's psychiatric and mild neurodevelopmental disorders.

MicroRNA expression profiling and functional annotation analysis of their targets modulated by oxidative stress during embryonic heart development in diabetic mice

Maternal pregestational diabetes mellitus (PGDM) induces congenital heart defects (CHDs). The molecular mechanism underlying PGDM-induced CHDs is unknown. microRNAs (miRNAs), small non-coding RNAs, repress gene expression at the posttranscriptional level and play important roles in heart development. We performed a global miRNA profiling study to assist in revealing potential miRNAs modulated by PGDM and possible developmental pathways regulated by miRNAs during heart development. A total of 149 mapped miRNAs in the developing heart were significantly altered by PGDM. Bioinformatics analysis showed that the majority of the 2111 potential miRNA target genes were associated with cardiac development-related pathways including STAT3 and IGF-1 and transcription factors (Cited2, Zeb2, Mef2c, Smad4 and Ets1). Overexpression of the antioxidant enzyme, superoxide dismutase 1, reversed PGDM-altered miRNAs, suggesting that oxidative stress is responsible for dysregulation of miRNAs. Thus, our study provides the foundation for further investigation of a miRNA-dependent mechanism underlying PGDM-induced CHDs.

Neuroscience and the Law

We conducted a systematic review and meta-analysis to evaluate the association between parental diabetes mellitus and the risk of ADHD in offspring. The PubMed, EMBASE, Cochrane, and Web of Science databases were searched from inception to May 31, 2019. Thirteen observational studies containing 5,052,736 participants were included. Two reviewers independently extracted data and assessed the quality of the studies using predefined standard procedures. Random-effects model were used. We found that maternal pregestational diabetes mellitus (PGDM) was associated with an increased risk of ADHD in offspring (odds ratio [OR]: 1.40; 95% confidence interval [CI]:1.31–1.50) in adjusted analyses. Increased risks of ADHD in offspring were also observed among those with maternal preexisting type 1 diabetes (T1D) (OR: 1.39; 95% CI: 1.27–1.52) and paternal T1D (OR: 1.20; 95% CI: 1.13–1.28) in adjusted analyses. Sensitivity analyses supported the robustness of our findings. Future studies should use robust designs to address whether the association with parental diabetes mellitus is causal.

The accuracy of population health data for monitoring trends and outcomes among women with diabetes in pregnancy

Aim To assess the accuracy of routinely collected population birth and hospital datasets in identifying maternal pregestational diabetes mellitus (PDM) and gestational diabetes mellitus (GDM). Methods Information on maternal diabetes status was obtained from the medical records of a random sample of 1200 women and compared with routinely collected, population-based birth and hospital data. PDM and GDM are reported in both databases. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and the kappa statistic were determined. Results Medical records were available for 1184 of the 1200 women sampled. 0.3% of women were classified with PDM and 4.8% with GDM. ‘True’ PDM was under-reported and misclassified in the birth data, but all cases were reported in the hospital data. GDM was also more completely and more accurately reported in the hospital data than in the birth data. Diabetes requiring insulin was more likely to be reported than non-insulin dependent diabetes. Conclusions Hospital data were more sensitive and accurate (higher PPVs) than birth data and these measures were not improved by ascertaining diabetes from either of the two datasets. More severe forms of diabetes were more likely to be reported than less severe.

Infrequently studied congenital anomalies as clues to the diagnosis of maternal diabetes mellitus

The aim of this study was to identify congenital anomalies (CA) among infants of women with diabetes mellitus (DM) that, even though infrequent or infrequently reported, may suggest diabetic teratogenesis. Using 1976-2005 data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we compared the frequency of selected CA among 130 infants with CA born to women with pregestational DM (PGDM) and 30,009 infants with CA whose mothers had normal glucose tolerance (NGT). To identify which CA were not only significantly more frequent among infants of mothers with PGDM, but also more specific, we calculated the quotient of their frequencies (frequency ratio: FR). The same analysis was made using data from 927 infants of mothers with gestational DM (GDM). Among the studied defects, several were statistically significantly more frequent among infants of PGDM mothers than among infants of mothers with NGT, although the specificity of their association with DM varied, as indicated by the values of the FR. These included: anorectal atresia/stenosis (FR = 2.81; P = 0.03), hallucal polydactyly (FR = 3.62; P = 0.002), heterotaxy (FR = 5.70; P = 0.049), hypertrophic cardiomyopathy (HCM) (FR = 61.60; P = 0.000000), multicystic dysplastic kidneys (MDK) (FR = 5.13; P = 0.0002), and thymus aplasia/hypoplasia (FR = 29.62; P = 0.000001). The only CA significantly more frequent among infants of women with GDM were HCM (FR = 8.60; P = 0.002) and MDK (FR = 1.80; P = 0.01). Our results suggest that maternal PGDM should be suspected in children with hallucal polydactyly, anorectal atresia/stenosis, heterotaxy, or aplasia/hypoplasia of the thymus. The presence of transient HCM or MDK in a newborn suggests maternal PGDM or GDM. These observations are important in view of the increasing worldwide frequency of DM and the high proportion of individuals with DM in whom the condition remains undiagnosed. (c) 2007 Wiley-Liss, Inc.