Pregestational Diabetic Pregnancies Research Articles

The value of Middle cerebral and umbilical arteries Doppler indices in pregestational diabetic versus normal pregnancies in prediction of adverse neonatal outcome

The value of Middle cerebral and umbilical arteries Doppler indices in pregestational diabetic versus normal pregnancies in prediction of adverse neonatal outcome

Evaluation of cardiac contractility of fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound.

This study aimed to evaluate cardiac contractility in fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode. A retrospective cross-sectional study was performed on 40 fetuses from nondiabetic pregnancies and 28 pregestational diabetic pregnancies between 20 and 33 weeks and 6 days. Cardiac contractility was assessed by measuring the ventricular myocardial area in diastole subtracted from the ventricular myocardial area in systole. Pregestational diabetic pregnancies had a lower maternal age than nondiabetic pregnancies (26.7 vs. 39.9 years, p=0.019). Cardiaccontractility in fetuses from diabetic and nondiabetic pregnancies was similar (p=0.293). A moderately positive and significant correlation was observed between gestational age and cardiac contractility (r=0.46, p=0.0004). A 1-week increase in gestational age was responsible for a 0.1386 cm2 increase in cardiac contractility. Cardiac contractility as evaluated by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode showed no significant differences across fetuses with and without pregestational diabetes.

The value of Middle cerebral and umbilical arteries Doppler indices in pregestational diabetic versus normal pregnancies in prediction of adverse neonatal outcome

The value of Middle cerebral and umbilical arteries Doppler indices in pregestational diabetic versus normal pregnancies in prediction of adverse neonatal outcome

Middle Cerebral Artery and Umbilical Artery Doppler Indices in Pre-gestational diabetic Versus Normal Pregnancies and Their Values in Predicting Adverse Neonatal Outcome

Middle Cerebral Artery and Umbilical Artery Doppler Indices in Pre-gestational diabetic Versus Normal Pregnancies and Their Values in Predicting Adverse Neonatal Outcome

Glycosylated haemoglobin as an indicator of diabetes control in pregnancy: A 10-year review of the relationship between HbA1c trends and delivery outcome in type I and type II diabetes

BackgroundPregestational diabetes mellitus (PGDM) confers an increased risk of adverse maternal and neonatal outcomes [1,2]. Glycaemic control in the medium and long term is commonly evaluated by examining glycosylated haemoglobin (HbA1c) levels. However, the value of HbA1c in pregnancy may be diminished by increased level of red cell turnover characteristic of pregnancy [3,4]. We sought to examine the impact of HbA1c in the first trimester and pre-delivery, and the within-patient change throughout gestation on mode of delivery and birthweight in pregnancies complicated by a pre-pregnancy diagnosis of type I or type II diabetes. MethodsA 10-year consecutive cohort of pregnancies complicated by PGDM, from Jan 2010 until Dec 2019, was examined for HbA1c data in the first trimester and within 6 weeks of delivery. Perinatal outcome data, including gestational age at delivery, mode of delivery and birthweight centile, were obtained from hospital records. The Spearman Rank correlation was used to correlate HcA1c levels in the first trimester with birthweight centiles. Non-parametric summaries and rank-based tests, Signed-rank test and Kruskal-Wallis test, were used to compare Hba1c levels. ResultsDuring the 10-year study period, a consecutive cohort of 396 pregnancies that attained a viable gestational age (>24 weeks’ gestation) and complicated by pregestational diabetes was identified; representing 81 % of the population of pregestational diabetic pregnancies managed by this service during the study period. The median [IQR] HbA1c levels (mmol/mol) in the first trimester, pre-delivery and the differential across gestation were 51 [19] mmol/mol, 43 [11] mmol/mol and −8 [13] mmol/mol, respectively. A statistically significant reduction in HbA1c levels throughout gestation was observed (p < 0.001). The median [IQR] birthweight centile was 69 [50 – 96]. The distributions in HbA1c levels and birthweight centiles were heavily skewed. No correlation was identified between HbA1c levels and mode of delivery. ConclusionNeither baseline HbA1c levels, pre-delivery values, nor trends across gestation appear to impact birthweight centile or mode of delivery in PGDM. While optimising glycaemic control can affect the long term health of the mother, these indices cannot be relied upon to reflect the impact of glycaemic control on fetal growth aberrations that influence mode of delivery.

The Role of Hemoglobin A1c Level in Prediction of Adverse Obstetric and Neonatal Outcomes in Pregestational Diabetic Pregnancies

The Role of Hemoglobin A1c Level in Prediction of Adverse Obstetric and Neonatal Outcomes in Pregestational Diabetic Pregnancies

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 statement What 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.

Placental changes in diabetic pregnancies and the contribution of hypertension

Objective To evaluate placental abnormalities in pregnancies affected by diabetes compared to unaffected pregnancies from a single academic center. Methods This is a retrospective cohort study of women with singleton gestations delivered at the University of Arkansas for Medical Sciences from 2007 to 2016. Pathologic examination of placentas from pregestational and gestational diabetic pregnancies were compared to placentas from patients without diabetes using 12 histologic elements. Maternal and neonatal outcomes were extracted from the medical record and compared between groups. Findings were adjusted for hypertensive disorders of pregnancy. Placental lesions were also correlated with diabetic control. Results Pathology reports of 590 placentas along with corresponding medical records were reviewed. The diabetic group (N = 484) consisted of 188 patients with pregestational diabetes and 296 patients with gestational diabetes. The nondiabetic group consisted of 106 patients. The diabetic group was older, had a higher average BMI, and more hypertensive disorders (p < .0001). Out of the 12 histologic elements investigated, accelerated villous maturation (aOR = 8.45, 95%CI (1.13–62.95)) and increased placental weight (aOR = 3.131, 95% CI (1.558–6.293)) were noted to be significantly increased in placentas from diabetic pregnancies after controlling for hypertension. Intervillous thrombi were not significantly increased in pregnancies affected by diabetes. Neonates of the diabetic group were more likely to be large for gestational age (p < .0001) and had a higher rate of preterm delivery (p < .0001). Conclusions Accelerated villous maturation was found to be more frequent in pregnancies complicated by pregestational diabetes, even after controlling for hypertension. In pregnancies complicated by gestational diabetes, the placental findings were not significant after controlling for hypertension. In contrast with prior studies, there was no increase in thrombotic lesions of the placenta in patients with diabetes.

224: Cesarean birth rates in pregestational diabetic pregnancies

Pregestational diabetes (PGDM) is increasing in the US and is associated with an increased risk of pregnancy complications, including cesarean birth. However, there are limited data regarding contributing factors to this increased CBR. This retrospective cohort study included chart abstracted data on births between 24+0-42+6 weeks’ estimated gestational age (EGA) at 21 hospitals participating in a multi-center quality collaborative between 01/2014 and 12/2018. Births complicated by gestational diabetes or with missing data for mode of delivery were excluded. CBR in women with PGDM were compared to CBR in women without diabetes using the Robson Ten Group Classification (TGC) system. The TGC system stratifies pregnancies in a population based on parity, plurality (multiple or singleton), presentation, EGA at birth, history of cesarean and labor status preceding delivery. CBR in each group were compared using univariate and multivariate logistic regression adjusting for age, BMI and race. Data are presented as OR’s and adjusted OR’s with 95% CI’s. The final study cohort comprised 99,727 births; 1,750 with PGDM and 97,979 without diabetes. The overall CBR was 58.5% in women with PGDM compared to 29.3% in women without diabetes (aOR 2.7, CI 2.4-3.0; Table 1). Across all TGC groups, the CBR was higher in women with PGDM than without diabetes, with the exception of those associated with term non-cephalic lie (Table 1). This study demonstrates a significantly increased CBR in women with PGDM compared to women without diabetes. The increased CBR in women with PGDM held true in those who underwent an intrapartum cesarean (Robson groups 1, 2a, 3, 4a), with rates nearly twice than in non-diabetic women. This information may be useful in counseling women with PGDM. Whether this increased CBR is due to fetal factors, uterine or cervical receptivity, or a difference in practitioner approach to labor in these women requires further investigation.

326: Placental changes in diabetic pregnancies and the contribution of hypertension

To evaluate placental abnormalities in pregnancies affected by diabetes compared to unaffected pregnancies from a single academic center This is a retrospective cohort study of women with singleton gestations delivered from 2007 to 2016. Pathologic examination of placentas from pregestational and gestational diabetic pregnancies were compared to placentas from patients without diabetes using twelve histologic elements. Maternal and neonatal outcomes were extracted from the medical record and compared between groups. Findings were adjusted for hypertensive disorders of pregnancy. Pathology reports of 590 placentas along with corresponding medical records were reviewed. The diabetic group (N=484) consisted of 188 patients with pregestational diabetes and 296 patients with gestational diabetes. The nondiabetic group consisted of 106 patients. The diabetic group was older, had a higher average BMI, and more hypertensive disorders (p< 0.0001). Out of the 12 histologic elements investigated, accelerated villous maturation (aOR 8.45, 95%CI (1.13-62.95)) and increased placental weight (aOR 3.131, 95% CI (1.558-6.293)) were noted to be significantly increased in placentas from diabetic pregnancies after controlling for hypertension. Intervillous thrombi were not significantly increased in pregnancies affected by diabetes. Neonates of the diabetic group were more likely to be large for gestational age (p< 0.0001) and had a higher rate of preterm delivery (p< 0.0001). Accelerated villous maturation was found to be more frequent in pregnancies complicated by diabetes. Accelerated villous maturation is a placental finding that indicates maternal vascular malperfusion. In contrast with prior studies, there was no increase in thrombotic lesions of the placenta in patients with diabetes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pilot Study of Ethnic Variation of Placental Pathology and Perinatal Outcomes in Pregestational Diabetic Pregnancy

Pilot Study of Ethnic Variation of Placental Pathology and Perinatal Outcomes in Pregestational Diabetic Pregnancy

Heart rate variability in neonates of type 1 diabetic pregnancy

BackgroundCardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. AimsOur aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. Study design and subjectsThis was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). Outcome measuresHeart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. ResultsNeonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (p<0.05). This altered HRV was significantly related to fetal acidaemia, cord blood glucose values and maternal glycaemic control during pregnancy (p<0.05). ConclusionNeonates of pregestational diabetic pregnancy have altered HRV which is related to maternal hyperglycaemia, fetal acidaemia and fetal glycaemia. Exposure of the developing heart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life.

P52. Prevalence of preeclampsia in patients of pre-gestational diabetic pregnancy in Bangladesh

Background Preeclampsia, sometimes referred to as toxemia or pregnancy-induced hypertension, is a disorder that occurs during pregnancy and affects both the mother and the fetus. It is a rapidly progressive condition characterized by elevated blood pressure, swelling and protein in the urine. The cause of preeclampsia is still not fully understood, though the disease was recognized and described nearly 2000 years ago. Pre-eclampsia and eclampsia is a cause of high morbidity and mortality for both mother and fetus especially in developing countries. Objective Preeclampsia (preE) is a pregnancy disorder characterized by the de novo development of hypertension and proteinuria with multiple path physiologic triggers and mechanisms. Approximately 20% of the diabetic pregnant women develop preE. The mechanisms contributing to this effect is not well characterized. In a recent study, we have shown that hyperglycemia impairs cytotrophoblast (CTB) function via stress signaling. Several researchers demonstrate a direct link between preE and diabetes. The objective of the study was to evaluate potential linkage between the risk of developing preE and the presence of diabetes in pregnant patients in Bangladesh. Methods This is a cross-sectional study of 270 pregnant women performed to evaluate the prevalence of PreE with respect to different risk factors such as previous pregnancy, presence of Antiphospholipid antibodies, pre-existing diabetes (before this pregnancy), multiple gestation / singleton, family history of preE in first degree relative (mother, sister and daughters; most commonly mother), maternal age of 40 or greater. The study was conducted in selected hospitals of Dhaka city, Bangladesh during October 2012 to December 2013. We gave special emphasis on the occurrence of PreE in pre-gestational diabetic patients. This study was approved by the Ethical review committee of Bangladesh Medical Association. Results The key study findings revealed that the rate of development of PreE in Bangladeshi pre-gestational diabetic patients is 27%. Conclusions There is an association has been found between the risk of developing preE and the presence of diabetes in pregnant patients in Bangladesh.

Listening to the patient[apos]s story: a qualitative approach to pre-gestational diabetic pregnancy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Novel placental ultrasound assessment: Potential role in pre-gestational diabetic pregnancy

ObjectivesManagement of women with pre-gestational diabetes continues to be challenging for clinicians. This study aims to determine if 3D power Doppler (3DPD) analysis of placental volume and flow, and calculation of placental calcification using a novel software method, differ between pregnancies with type 1 or type 2 diabetes and normal controls, and if there is a relationship between these ultrasound placental parameters and clinical measures in diabetics. MethodsThis was a prospective cohort study of 50 women with diabetes and 250 controls (12–40 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental calcification was calculated by computer analysis. Results in diabetics were compared with control values, and correlated with early pregnancy HbA1c, Doppler results and placental histology. ResultsPlacental calcification and volume increased with advancing gestation in pre-gestational diabetic placentae. Volume was also found to be significantly higher than in normal placentae. VI and VFI were significantly lower in diabetic pregnancies between 35 and 40 weeks gestation. A strong relationship was seen between a larger placental volume and both increasing umbilical artery pulsatility index and decreasing middle cerebral artery pulsatility index. FI was significantly lower in cases which had a booking HbA1c level ≥6.5%. Ultrasound assessed placental calcification was reduced with a histology finding of delayed villous maturation. No other correlation with placental histology was found. ConclusionsThis study shows a potential role for 3D placental evaluation, and computer analysis of calcification, in monitoring pre-gestational diabetic pregnancies.

Diabetic Pregnancy and Fetal Consequences

Perinatal morbidity and mortality, congenital malformations, abnormal fetal growth, both spontaneous and iatrogenic preterm birth, hypoxic complications, and trauma during delivery are increased in diabetic pregnancies. Perinatal mortality in diabetic pregnancies is still three to five times higher than the perinatal mortality in the general population. Stillbirths during the last weeks of pregnancy are often considered unexplained, although recent studies indicate that most of these stillbirths are caused by fetal chronic hypoxia. Importantly, perinatal mortality has not changed during the past 3 decades in diabetic pregnancies, which emphasizes the need to find new methods and strategies to improve perinatal outcome. Congenital malformations have decreased in pregestational diabetic pregnancies because of general improvement of glycemic control among diabetic women. However, the rate of fetal malformations is still two to four times higher in type 1 and type 2 diabetic pregnancies than in the general population. Prepregnancy counseling decreases the risk of fetal malformations. Efforts should be made to improve the attendance of diabetic women in prepregnancy clinics. Fetal overgrowth during the last trimester of pregnancy is the most common fetal complication in diabetic pregnancies. Accurate estimation of fetal weight by ultrasound is especially difficult in macrosomic fetuses. Magnetic resonance imaging can be used to assess fetal total volume, shoulder width, and fat amount in addition to obtaining accurate pelvic measurements. More studies on the clinical use of magnetic resonance imaging in obstetrics are urgently needed. Increased fetal erythropoietin (EPO) level is an indicator of fetal chronic hypoxia, which can be detected antenatally by measuring amniotic fluid EPO concentration. Sufficiently large controlled studies are needed before amniotic fluid EPO measurement can be recommended for clinical use.

Cardiomyopathy in offspring of pregestational diabetic mouse pregnancy.

Purpose. To investigate cardiomyopathy in offspring in a mouse model of pregestational type 1 diabetic pregnancy. Methods. Pregestational diabetes was induced with STZ administration in female C57BL6/J mice that were subsequently mated with healthy C57BL6/J males. Offspring were sacrificed at embryonic day 18.5 and 6-week adolescent and 12-week adult stages. The size and number of cardiomyocyte nuclei and also the extent of collagen deposition within the hearts of diabetic and control offspring were assessed following cardiac tissue staining with either haematoxylin and eosin or Picrosirius red and subsequently quantified using automated digital image analysis. Results. Offspring from diabetic mice at embryonic day 18.5 had a significantly higher number of cardiomyocyte nuclei present compared to controls. These nuclei were also significantly smaller than controls. Collagen deposition was shown to be significantly increased in the hearts of diabetic offspring at the same age. No significant differences were found between the groups at 6 and 12 weeks. Conclusions. Our results from offspring of type 1 diabetic mice show increased myocardial collagen deposition in late gestation and have increased myocardial nuclear counts (hyperplasia) as opposed to increased myocardial nuclear size (hypertrophy) in late gestation. These changes normalize postpartum after removal from the maternal intrauterine environment.

Fetal and maternal leptin in pre-gestational diabetic pregnancy

ObjectiveTo compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes. MethodsIn a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay. ResultsNo difference was found in maternal leptin among the groups: without diabetes (mean, range): 325pg/mL, 36–1492pg/mL; type 1 diabetes: 343.2pg/mL, 55.5–1108.2pg/mL; type 2 diabetes: 202.2pg/mL, 35.1–1553.3pg/mL (P>0.05). Leptin levels were higher among fetuses of women with type 1 (223pg/mL, 25.7–810pg/mL) and type 2 (447.2pg/mL, 136.3–679pg/mL) diabetes than among women without diabetes (80.3pg/mL, 27.3–623.1pg/mL; P<0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r=0.39, P=0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r=0.28, P=0.04). ConclusionFetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life.

Clinical and ultrasound features of placental maturation in pre-gestational diabetic pregnancy

BackgroundPre-gestational diabetes (PGDM) is a significant cause of neonatal morbidity and mortality. Delayed villous maturation (DVM) is a placental diagnosis with increased risk of perinatal mortality. AimsThis study aimed to prospectively look at the incidence of DVM in a PGDM population compared to non-diabetic controls. Additionally, we analysed antenatal ultrasound and clinical markers for DVM in the diabetic population. Study designThis is a prospective study. SubjectsPlacentae of women with non-diabetic and PGDM pregnancies underwent detailed blinded histo-pathological examination. Outcome measuresClinical data, including birth weight, peri-natal outcome, and, in PGDM group, glycaemic control and ultrasound findings, were obtained. Results77 non-diabetic women and 74 PGDM women consented to the study. The incidence of DVM in the PGDM group was higher than in the non-diabetic group (21/74 (28.4%) vs. 11/77 (14.3%) p=0.02; RR 1.98). In the PGDM group clinical and ultrasound markers were compared between the DVM group (n=21) and the non‐DVM group (n=53). There was no difference in perinatal outcome nor glycaemic control between these two groups. ConclusionDVM, a placental finding with an increased risk of perinatal mortality, is increased in PGDM population compared to non-diabetic controls. No association was found with maternal glycaemic control. The presence of placental DVM was not associated with antenatal ultrasound parameters nor clinical perinatal outcome.

The Impacts of Maternal Gestational Diabetes Mellitus (GDM) on Fetal Hearts

ObjectiveTo evaluate the fetal cardiac function in gestational diabetes mellitus (GDM) pregnancies under different maternal glycemic controls. MethodsForty four GDM mothers received 78 fetal echocardiographic evaluations at three gestational periods (<28, 28-34 and ⩾34 weeks) and were divided into poorly-(DM1) and well-(DM2) controlled groups according to their glycemic control at examination. Seventy uncomplicated mothers were selected as controls. Parameters of fetal cardiac anatomy and function were measured and analyzed. ResultsGDM fetuses' cardiac ventricular walls were thicker than controls', and the differences between DM1 and DM2 were not significant except for end-diastolic left ventricular walls. In both GDM groups, the aortic flow velocities increased earlier than pulmonary artery and DM1 fetuses changed earlier than DM2 ones. GDM fetuses' left atrial shortening fraction was smaller than the controls' in the period of ⩾34 weeks and negatively correlated with thicknesses of left ventricular walls and interventricular septum in DM1 fetuses (r=−0.438 and −0.506). The right ventricular diastolic function in DM1 and DM2 fetuses decreased after the period of 28-34 weeks and in the period of ⩾34 weeks respectively. Tei index of both left and right ventricles increased in DM1 group after the period of <28 weeks and in DM2 group only in the period of ⩾34 weeks, with no significant differences between DM1 and DM2 groups in this period. ConclusionFetuses of GDM mothers showed cardiac function impairments. Good maternal glycemic control may delay the impairments, but cannot reduce the degree. Some cardiac changes in GDM fetuses were similar to those in pregestational diabetic pregnancies except for several parameters and their changing time.