Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring.

LAY ABSTRACT: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

The effect of different forms of dysglycemia during pregnancy on maternal and fetal outcomes in treated women and comparison with large cohort studies.

AIMS OF THE STUDY: We describe the impact of different forms of dysglycemia on maternal and neonatal health. This research is a part of the PEARL-Peristat Maternal and newborn registry, funded by Qatar National Research Fund (QNRF) Doha, Qatar. METHODS: A population-based retrospective data analysis of 12,255 women with singleton pregnancies screened during the year 2016-2017, of which 3,027 women were identified with gestation diabetes mellitus (GDM) during pregnancy and 233 were diabetic before pregnancy. Data on maternal outcome was collected from the PEARL-Peristat Maternal and newborn registry. RESULTS: The prevalence of GDM and diabetes mellitus (DM) was 24.7 % and 1.9%, respectively. 55% of DM, 38% of GDM and 25.6% of controls were obese (p<0.001). 71% of pregnant women with DM and 57.8% of those with GDM were older than 30 years versus 44.2% of controls. Pregnant women with DM or GDM had higher prevalence of hypertension versus normal controls (9.9%, 5.5% and 3.5%, respectively; p<0.001). Among women with vaginal deliveries, the proportion of women with induction of labor was significantly higher in the DM and GDM compared to control subjects (33.9%, 26.5% and 12.4%, respectively; p<0.001). The number of women who underwent Cesarean section was significantly higher in the DM and GDM groups versus normal controls (51.9%, 36.8%, and 28.5%, respectively; p<0.001).  Preterm delivery was significantly higher in women with DM and GDM (13.7% and 9%, respectively versus normal women (6.4%); p<0.001). Babies of DM and GDM had significantly higher occurrence of respiratory distress (RDS) or transient tachypnea (TTS): 9% and 5.8 % versus normal controls (4.8%). Macrosomia was more prevalent in babies of DM (6.4%) and GDM (6.8%) compared to controls (5%) (p: <0.001). Significant hypoglycemic episodes occurred more frequently in babies of DM and GDM women (11.2% and 3%, respectively) versus controls (0.6%) (p: <0.001. Infants of DM and GDM mothers required more treatments of phototherapy (9.4% and 8.9%, respectively) versus those born to normal women (7.2%) (p: 0.006). The prevalence of congenital anomalies and neonatal death did not differ between the groups. CONCLUSIONS: Despite the improvement in the prenatal diagnosis and management of dysglycemia, there is still a higher prevalence of prematurity, macrosomia, and hypoglycemia in infants of mothers with DM and GDM. Measurements to reduce obesity and control dysglycemia in women during the childbearing period are highly required to prevent the still higher morbidity during pregnancy.

Trends and racial and ethnic disparities in the prevalence of pregestational type 1 and type 2 diabetes in Northern California: 1996-2014.

BACKGROUND: Despite concern for adverse perinatal outcomes in women with diabetes mellitus before pregnancy, recent data on the prevalence of pregestational type 1 and type 2 diabetes mellitus in the United States are lacking. OBJECTIVE: The purpose of this study was to estimate changes in the prevalence of overall pregestational diabetes mellitus (all types) and pregestational type 1 and type 2 diabetes mellitus and to estimate whether changes varied by race-ethnicity from 1996-2014. STUDY DESIGN: We conducted a cohort study among 655,428 pregnancies at a Northern California integrated health delivery system from 1996-2014. Logistic regression analyses provided estimates of prevalence and trends. RESULTS: The age-adjusted prevalence (per 100 deliveries) of overall pregestational diabetes mellitus increased from 1996-1999 to 2012-2014 (from 0.58 [95% confidence interval, 0.54-0.63] to 1.06 [95% confidence interval, 1.00-1.12]; Ptrend <.0001). Significant increases occurred in all racial-ethnic groups; the largest relative increase was among Hispanic women (121.8% [95% confidence interval, 84.4-166.7]); the smallest relative increase was among non-Hispanic white women (49.6% [95% confidence interval, 27.5-75.4]). The age-adjusted prevalence of pregestational type 1 and type 2 diabetes mellitus increased from 0.14 (95% confidence interval, 0.12-0.16) to 0.23 (95% confidence interval, 0.21-0.27; Ptrend <.0001) and from 0.42 (95% confidence interval, 0.38-0.46) to 0.78 (95% confidence interval, 0.73-0.83; Ptrend <.0001), respectively. The greatest relative increase in the prevalence of type 1 diabetes mellitus was in non-Hispanic white women (118.4% [95% confidence interval, 70.0-180.5]), who had the lowest increases in the prevalence of type 2 diabetes mellitus (13.6% [95% confidence interval, -8.0 to 40.1]). The greatest relative increase in the prevalence of type 2 diabetes mellitus was in Hispanic women (125.2% [95% confidence interval, 84.8-174.4]), followed by African American women (102.0% [95% confidence interval, 38.3-194.3]) and Asian women (93.3% [95% confidence interval, 48.9-150.9]). CONCLUSIONS: The prevalence of overall pregestational diabetes mellitus and pregestational type 1 and type 2 diabetes mellitus increased from 1996-1999 to 2012-2014 and racial-ethnic disparities were observed, possibly because of differing prevalence of maternal obesity. Targeted prevention efforts, preconception care, and disease management strategies are needed to reduce the burden of diabetes mellitus and its sequelae.

[Diabetes in Pregnancy - Type 1/Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus]. / Diabetes in der Schwangerschaft.

In Germany in 5.5% of all births diabetes is registered. In patients with type 1 and type 2 diabetes planning pregnancy, preconception counseling, diabetologic care with optimized periconceptional metabolic control and folic acid supplementation are essential for good pregnancy outcome. Gestational diabetes (GDM) should be diagnosed timely and managed according to existing guidelines. GDM is treated with insulin in approximately 20%. In 1-2% of GDM cases a glucokinase gene mutation is present (MODY 2). Pregnancies after bariatric-metabolic surgery are increasing and show high risks.

Maternal risk factors involved in specific congenital anomalies of the kidney and urinary tract: A case-control study.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a heterogeneous group of birth defects with a variety of genetic and nongenetic factors suspected of involvement in the etiology. However, little is known about risk factors in specific CAKUT phenotypes. Therefore, we studied potential maternal risk factors in individual phenotypes within the CAKUT spectrum. METHODS: Questionnaire data were collected from parents of 562 children with CAKUT and 2139 healthy controls within the AGORA data- and biobank. Potential maternal risk factors investigated included folic acid use, overweight and obesity, smoking, alcohol consumption, subfertility, and diabetes mellitus. We performed logistic regression analyses to assess associations between these potential risk factors and CAKUT phenotypes. RESULTS: Increased risks of CAKUT were observed for folic acid use and maternal obesity, while fertility treatment by in vitro fertilization or intrauterine insemination and diabetes diagnosed during pregnancy also seem to be associated with CAKUT. Use of multivitamins reduced the risk (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.2-1.0) as opposed to use of folic acid supplements only (OR, 1.3; 95% CI, 1.0-1.8). Folic acid use was associated with duplex collecting systems (OR, 1.8; 95% CI, 1.0-3.4) and vesicoureteral reflux (OR, 1.8; 95% CI, 1.1-2.9) in particular. A relatively strong association was observed between diabetes during pregnancy and posterior urethral valves (OR, 2.6; 95% CI, 1.1-5.9). CONCLUSION: Use of folic acid only seems to be counterproductive for prevention of CAKUT, in contrast to multivitamin use. Furthermore, we observed differences in risk factor patterns among CAKUT phenotypes, which stress the importance of separate analyses for each phenotype. Birth Defects Research (Part A) 106:596-603, 2016. © 2016 Wiley Periodicals, Inc.

[Costs of temporary disability in Spain related to diabetes mellitus and its complications]. / Costes por incapacidad temporal en España derivados de la diabetes mellitus y sus complicaciones.

INTRODUCTION AND OBJECTIVES: To ascertain the socioeconomic impact of diabetes, it is essential to estimate overall costs, including both direct and indirect costs (premature retirements, working hours lost, or sick leaves). This study analyzed indirect costs for temporary disability (TD) due to diabetes and its complications in Spain in 2011 by assessing the related ICD-9 MC codes. MATERIAL AND METHOD: For this purpose, the number of TD processes and their mean duration were recorded. The indirect costs associated to loss of working days were also estimated. RESULTS: In 2011, diabetes and its complications were related to 2.567 TD processes, which resulted in the loss of 154.214 days. In terms of costs, this disease represented for Spanish public health administrations an expense of 3,297.095.3 €, with an estimated cost per patient and year of 141 €. CONCLUSIONS: These data suggest an urgent need to devise plans for prevention and early diagnosis of diabetes and its complications, as well as programs to optimize the available health care resources by creating multidisciplinary teams where occupational medical services assume an important role. A decrease in absenteeism would result in benefits for diabetic patients, society overall, and companies or public institutions.

[Characterization of folate supplementation in pregnancy, based on a combination of health information systems]. / Caracterización de la suplementación de folatos en el embarazo a partir de la combinación de sistemas de información sanitaria.

OBJECTIVES: To explore the utility of combining health information systems from the Valencia Health Agency to characterize folate supplementation in pregnant women in the autonomous region of Valencia (Spain). METHODS: The cohort comprised women who gave birth during 2009 in hospitals within the Valencian Health Agency. These women were retrospectively followed-up using ABUCASIS electronic medical records and the GAIA electronic prescription system to identify folate consumption in the 3 months before and after conception. RESULTS: In 2009, there were 38,069 births in hospitals of the Valencian Health Agency, of which 37,040 (97.3%) were included for analysis. In 34% of women, at least one folate dispensation was registered with an official prescription form within the periconceptional period (6.6% in the 3 months prior to conception). Dispensation with an official prescription form was associated with older women, free pharmaceutical prescriptions, birth in Spain, antiepileptic medications, and a diagnosis of diabetes. Eight percent of women (23.6% of the folate-treated women) received folates at high doses. CONCLUSIONS: Folate consumption during pregnancy is systematically under-registered by healthcare information systems because health professionals do not use the official prescription form for prescription and dispensation. Database linkage is an inadequate approach to assess folic acid supplementation during pregnancy.

Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects.

OBJECTIVE: The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. STUDY DESIGN: The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. RESULTS: The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. CONCLUSION: The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus.

Neonatal small left colon syndrome in the offspring of diabetic mothers-an analysis of 105 children.

BACKGROUND AND AIM: Neonatal small left colon syndrome (NSLCS) is considered a rare cause of neonatal intestinal obstruction, with few documented cases in the English literature. Maternal diabetes has been reported in 40% to 50% of the published cases of NSLCS. Currently, the incidence of maternal diabetes is increasing, but there has been no study to ascertain the incidence and significance of NSLCS in this population. This review aims to assess the current significance of NSLCS and its association with maternal diabetes. MATERIALS AND METHOD: This was a retrospective review of 105 offspring of diabetic mothers who were admitted during the period 2004 to 2008 to our neonatal unit with special emphasis on associated NSLCS. RESULTS: There were 6 cases of intestinal obstruction in this group of 105 children. Five children, including a pair of twins, had classic features of NSLCS as demonstrated in the contrast enema with an abrupt transition at the splenic flexure and a narrow left colon. Conservative treatment was successful in all, negating the need for further invasive investigation. The sixth child had rectosigmoid Hirschprung disease. During the study period, there were no other cases of NSLCS in the nondiabetic population. CONCLUSION: Neonatal small left colon syndrome is the most common cause of intestinal obstruction in offspring of diabetic mothers. Neonatal small left colon syndrome can be confidently diagnosed in this population based on the classic clinical and radiologic findings. The incidence of NSLCS can be expected to increase as the incidence of maternal diabetes increases.

Recent studies on neural tube defects in embryos of diabetic pregnancy: an overview.

Maternal diabetes develops in 2-6% of total pregnancies, depending on geographical and ethnic background. About 10% of fetuses from diabetic pregnancy display congenital malformations in various organ systems including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects (NTDs) such as anencephaly, holoprosencephaly and syntelencephaly were more frequently demonstrated. Recent studies by the Diabetes Control and Complications Trial Research Group show that tight glycemic control early in pregnancy decreases the progression of a number of diabetic complications. However, it appears that the pre-existing tissue damage cannot be reversed even after normoglycemic levels are achieved during pregnancy. In recent years, considerable efforts have been made to investigate the etiology of birth defects among infants of diabetic mothers. It has been shown that diabetes-induced fetal abnormalities are accompanied by some metabolic disturbances including elevated superoxide dismutase (SOD) activity, reduced levels of myoinositol and arachidonic acid and inhibition of the pentose phosphate shunt pathway. Moreover, the frequency of fetal malformations in diabetic pregnancy has been reported to be markedly reduced by dietary supplements of antioxidants such as vitamin E, vitamin C and butylated hy- droxytoluene, suggesting that oxidative stress is involved in the etiology of fetal dysmorphogenesis. Furthermore, several experimental studies have shown that NTDs in embryos of diabetic mice are associated with altered expression of genes, which control development of the neural tube. In this review, recent findings of possible molecular mechanisms which cause morphological changes during neural tube development in embryos of diabetic pregnancy are discussed.

Current significance of meconium plug syndrome.

BACKGROUND: The significance of meconium plug syndrome is dependent on the underlying diagnosis. The incidence of pathologic finding, particularly Hirschsprung's disease, contributing to the presence of these plugs, has been debated. However, there are little recent data in the literature. Therefore, we reviewed our experience with meconium plugs as a cause of abdominal distension to evaluate the associated conditions and incidence of Hirschsprung's disease. METHODS: We reviewed the records of newborns with meconium plugs found in the distal colon on contrast enema from 1994 to 2007. Demographics, radiologic findings, histologic findings, operative findings, and clinical courses were reviewed. RESULTS: During the study period, 77 patients were identified. Mean gestational age was 37.4 weeks and birth weight, 2977 g. Hirschsprung's disease was found in 10 patients (13%). One had ultrashort segment disease and another had total colonic aganglionosis. Maternal diabetes was identified in 6 patients. No patients were diagnosed with cystic fibrosis, meconium ileus, malrotation, or intestinal atresia. CONCLUSION: Meconium plugs found on contrast enema are associated with a 13% incidence of Hirschsprung's disease in our experience. Although all patients with plugs and persistent abnormal stooling patterns should prompt a rectal biopsy and genetic probe, the incidence of Hirschsprung's and cystic fibrosis may not be as high as previously reported.

Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands.

OBJECTIVE: To investigate maternal, perinatal, and neonatal outcomes of pregnancies in women with type 1 diabetes in the Netherlands. DESIGN: Nationwide prospective cohort study. SETTING: All 118 hospitals in the Netherlands. PARTICIPANTS: 323 women with type 1 diabetes who became pregnant between 1 April 1999 and 1 April 2000. MAIN OUTCOME MEASURES: Maternal, perinatal, and neonatal outcomes of pregnancy. RESULTS: 84% (n = 271) of the pregnancies were planned. Glycaemic control early in pregnancy was good in most women (HbA(1c) < or = 7.0% in 75% (n = 212) of the population), and folic acid supplementation was adequate in 70% (n = 226). 314 pregnancies that went beyond 24 weeks' gestation resulted in 324 infants. The rates of pre-eclampsia (40; 12.7%), preterm delivery (101; 32.2%), caesarean section (139; 44.3%), maternal mortality (2; 0.6%), congenital malformations (29; 8.8%), perinatal mortality (9; 2.8%), and macrosomia (146; 45.1%) were considerably higher than in the general population. Neonatal morbidity (one or more complications) was extremely high (260; 80.2%). The incidence of major congenital malformations was significantly lower in planned pregnancies than in unplanned pregnancies (4.2% (n = 11) v 12.2% (n = 6); relative risk 0.34, 95% confidence interval 0.13 to 0.88). CONCLUSION: Despite a high frequency of planned pregnancies, resulting in overall good glycaemic control (early) in pregnancy and a high rate of adequate use of folic acid, maternal and perinatal complications were still increased in women with type 1 diabetes. Neonatal morbidity, especially hypoglycaemia, was also extremely high. Near optimal maternal glycaemic control (HbA1c < or = 7.0%) apparently is not good enough.

Factor analysis, including antihypertensive medication, of the outcome of pregnancy in pregnancy-associated hypertension.

AIM: To study the influence of different maternal factors, including antihypertensive medication, on the outcome of pregnancy in primi- and multiparas with pregnancy-associated hypertension. METHODS: A retrospective, multiple-variate analysis was undertaken of the influence of several maternal factors, including antihypertensive medication, on fetal death and Apgar scores and the correlation between the medication and the number of caesarean sections in 127 episodes of pregnancy-associated hypertension was studied for the whole group as well as for primi- and multiparas separately. Of the multiparas, 40.8% had a history of preeclampsia, 19.7% of chronic hypertension and 9.2% of diabetes mellitus. Antihypertensive treatment aimed at achieving a blood pressure of 140/90 mm Hg. Forty-one patients (32.3%) received intravenous hydralazine, 25 (19.7%) received nifedipine per os and 44 (34.6%) received labetalol per os. RESULTS: The maximum systolic and diastolic blood pressure in the patients given intravenous hydralazine, nifedipine per os or labetalol per os did not differ, whereas in the multiparas, the number of patients who reached the target blood pressure while using labetalol was higher than with the two other medications, especially in comparison with intravenous hydralazine. For the primiparas, the time of delivery was the only factor with a significant impact on the Apgar scores. In the multiparas, there was an additional negative influence of the use of intravenous hydralazine. This was not seen in the patients using nifedipine and labetalol. CONCLUSIONS: The results suggest that in multiparas, intravenous hydralazine is possibly associated with more fetal distress when compared to primiparas.