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

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

Differences in Hemoglobin A1c during Pregnancy between Non-Hispanic Black versus White Women with Prepregnancy Diabetes.

OBJECTIVE: The objective of this was to determine whether the change in hemoglobin A1c (HbA1c) from early to late pregnancy differs between non-Hispanic Black and White women with prepregnancy diabetes. STUDY DESIGN: A retrospective analysis was performed from an integrated prenatal and diabetes care program from 2012 to 2016. We compared HbA1c as a continuous measure and secondarily, HbA1c <6.5%, cross-sectionally, and longitudinally in early (approximately 10 weeks) and late (approximately 31 weeks) pregnancies. Linear and logistic regression were used and adjusted for age, body mass index, White diabetes class, medication use, diabetes type, gestational age at baseline HbA1c measurement, and baseline hemoglobin. RESULTS: Among 296 non-Hispanic Black (35%) and White pregnant women (65%) with prepregnancy diabetes (39% type 1 and 61% type 2), Black women were more likely to experience increased community-level social determinants of health as measured by the Social Vulnerability Index (SVI) and were less likely to have type 1 diabetes and have more severe diabetes versus White women (p < 0.05). Black women had higher mean HbA1c (7.8 vs. 7.4%; beta: 0.75; 95% confidence interval [CI]: 0.30-1.19) and were less likely to have HbA1c < 6.5% at 10 weeks compared with White women (24 vs. 35%; adjusted odds ratio: 0.45; 95% CI: 0.24-0.81) but not after adjusting for SVI. At 31 weeks, both groups had similar mean HbA1c (both 6.5%) and were equally as likely to have HbA1c < 6.5% (57 vs. 54%). From early to late pregnancy, Black women had a higher percentage decrease in HbA1c (1.3 vs. 0.9%; beta = 0.63; 95% CI: 0.27-0.99) and were equally as likely to have an improvement or stable HbA1C < 6.5% from 10 to 31 weeks, with both groups having a similar mean HbA1c (6.5%) at 31 weeks. CONCLUSION: Despite experiencing greater community-level social determinants of health, Black women with pregestational diabetes had a larger reduction in HbA1c and were able to equally achieve the target of HbA1c < 6.5% by late pregnancy compared with White women as part of an integrated diabetes and prenatal care program. KEY POINTS: · An integrated diabetes and pregnancy care program may decrease racial and ethnic disparities in glycemic control.. · Black women had a larger reduction in HbA1c versus White women.. · Black women were able to equally achieve the target of HbA1c < 6.5% by late pregnancy versus White women..

Amniotic Fluid Proteasome and Immunoproteasome in the Setting of Intra-Amniotic Infection, Inflammation, and Preterm Birth.

Preterm birth is an important determinant of neonatal morbidity and mortality and intra-amniotic infection (IAI) and inflammation play a causative role. The constitutive proteasome and immunoproteasome are key players in maintenance of proteostasis and their alteration outside pregnancy has been linked to pathogenesis of numerous inflammatory diseases. Our goal was to evaluate the levels, activities, and potential origin of amniotic fluid (AF) proteasome in women with preterm birth induced by infection and/or inflammation. Total proteasome and immunoproteasome concentrations were measured in AF retrieved by trans-abdominal amniocentesis from 155 pregnant women. Proteasome activities were measured with fluorogenic substrates targeting caspase-like (CAS-L), trypsin-like (TRY-L), or chymotrypsin-like (CHE-L) lytic activities. We found that IAI significantly upregulated AF concentrations of total proteasome and of the immunoproteasome (P<0.001 for both) with no differences based on gestational age. Based on substrate preference and profile of pharmacologic inhibition, we identified the CHE-L activity of the immunoproteasome as the primary lytic activity upregulated in AF of pregnancies complicated by IAI. When compared with matched maternal blood and cord blood, proteasome activity was by far the highest in AF and this was further elevated in IAI. Western blot confirmed ß5 (PSMB5) and ß5i (PSMB8) subunits of the constitutive proteasome and immunoproteasome are present in AF and IHC staining of fetal membranes pointed to chorio-decidua as a potential source. In conclusion, IAI is associated with increased AF immunoproteasome activity that by analogy with other inflammatory diseases may generate antigenic oligopeptides and may play a role in triggering preterm birth.

The use of longitudinal hemoglobin A1c values to predict adverse obstetric and neonatal outcomes in pregnancies complicated by pregestational diabetes.

BACKGROUND: Although an elevated early pregnancy hemoglobin A1c has been associated with both spontaneous abortion and congenital anomalies, it is unclear whether A1c assessment is of value beyond the first trimester in pregnancies complicated by pregestational diabetes. OBJECTIVE: We sought to investigate the prognostic ability of longitudinal A1c assessment to predict obstetric and neonatal adverse outcomes based on degree of glycemic control in early and late pregnancy. MATERIALS AND METHODS: This was a retrospective cohort study of all pregnancies complicated by pregestational diabetes from January 2012 to December 2016 at The Ohio State University Wexner Medical Center with both an early A1c (<20 weeks' gestation) and late A1c (>26 weeks' gestation) available for analysis. Patients were categorized by good (early and late A1c <6.5%), improved (early A1c >6.5% and late A1c <6.5%) and poor (late A1c >6.5%) glycemic control. A multivariate regression model was used to calculate adjusted odds ratios (aOR) for each identified obstetric and neonatal outcome, controlling for maternal age, body mass index, race/ethnicity, type of diabetes, and gestational age at delivery compared to good control as the referent group. RESULTS: A total of 341 patients met inclusion criteria during the study period. The median A1c values improved from early to late gestation in the good (5.7% [interquartile range [IQR], 5.4-6.1%] versus 5.4%; [IQR 5.2-5.7%]), improved (7.5% [IQR, 6.7-8.5] versus 5.9% [IQR, 5.6-6.1%]) and poor (8.3% [IQR, 7.1-9.6%] versus 7.3% [IQR, 6.8-7.9%]) glycemic control groups. There were no statistically significant differences in the rate of adverse outcomes between the good and improved groups except for an increased rate of neonatal intensive care unit admissions in the improved group (aOR, 3.7; confidence interval [CI], 1.9-7.3). In contrast, the poor control group had an increased rate of shoulder dystocia (aOR, 6.8; CI, 1.4-34.0), preterm delivery (aOR, 3.9; CI, 2.1-7.3), neonatal intensive care unit admission (aOR, 2.8; CI, 1.4-5.3), respiratory distress syndrome (aOR, 3.0; CI, 1.1-8.0), hypoglycemia (aOR, 3.2; CI, 1.5-6.9), large for gestational age weight at birth (aOR, 2.7; CI, 1.5-4.9), neonatal length of stay >4 days (aOR, 3.1; CI, 1.6-6.0) and preeclampsia (aOR, 2.4; CI, 1.2-4.6). There were no differences in rates of cesarean delivery, umbilical artery pH <7.1, or Apgar score <7 at 5 minutes after regression analysis. CONCLUSION: Antenatal hemoglobin A1c values are useful for objective risk stratification of patients with pregestational diabetes. Strict glycemic control throughout pregnancy with a late pregnancy A1c target of <6.5% leads to reduced rates of obstetric and neonatal adverse outcomes independent of early pregnancy glucose control.

Use of birth weight- vs. ultrasound-derived fetal weight classification methods: implications for detection of abnormal umbilical artery Doppler.

Objectives To compare a birth weight-derived (Brenner) and multiple ultrasound-derived [Hadlock, National Institute of Child Health and Human Development (NICHD), International Fetal and Newborn Growth Consortium (INTERGROWTH)] classification systems' frequency of assigning an antenatal estimated fetal weight (EFW) <10% and subsequent detection rate for abnormal umbilical artery Doppler (UAD). Methods We analyzed 569 consecutive non-anomalous singleton gestations identified by ultrasound with either an abdominal circumference (AC) <3% or EFW <10% at a tertiary medical center between 1/2012 and 12/2016. The biometric measurements were exported for all serial ultrasounds and the sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC) were calculated for the diagnosis of any abnormal UAD, absent or reversed end-diastolic flow (AREDF), and small for gestational age (SGA) for each classification method. Results Brenner classified less patients with EFW <10% (49.7%) vs. the comparison methods (range: 84.2-85.0%; P < 0.001). The sensitivity was highest using Hadlock for detection of any abnormal UAD [96.6%; confidence interval (CI) 92.8-98.8%], AREDF (100%; CI 95.1-100%), and SGA (89.0%; CI 85.4-91.6%). However, there was minimal variation between the Hadlock, NICHD, and INTERGROWTH methods for detection of the studied outcomes. The AUCs for any abnormal UAD, AREDF, and SGA were highest for the Brenner method, but there were a substantial number of false-negative results with lower overall detection rates. Conclusions Use of a birth weight-derived method to assign a fetal weight <10% as the threshold to initiate UAD surveillance has a lower detection rate for abnormal UAD when compared to ultrasound-derived methods. Despite substantial methodological differences in the creation of the Hadlock, NICHD, and INTERGROWTH methods, there were no differences in the detection rates of abnormal UAD.

The Accuracy and Cost-Effectiveness of Selective Fetal Echocardiography for the Diagnosis of Congenital Heart Disease in Patients with Pregestational Diabetes Stratified by Hemoglobin A1c.

OBJECTIVE: To evaluate the accuracy of antenatal diagnosis of congenital heart disease (CHD) using screening methods including a combination of elevated hemoglobin A1c, detailed anatomy ultrasound, and fetal echocardiography. STUDY DESIGN: This is a retrospective cohort study of all pregnancies complicated by pregestational diabetes from January 2012 to December 2016. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each screening regimen. The incremental cost-effectiveness ratio (ICER) was calculated for each regimen with effectiveness defined as additional CHD diagnosed. RESULTS: A total of 378 patients met inclusion criteria with an overall prevalence of CHD of 4.0% (n = 15). When compared with a detailed ultrasound, fetal echocardiography had a higher sensitivity (73.3 vs. 40.0%). However, all cases of major CHD were detected by detailed ultrasound (n = 6). Using an elevated early A1c > 7.7% and a detailed ultrasound resulted in a sensitivity and specificity of 60.0 and 99.4%, respectively. The use of selective fetal echocardiography for an A1c > 7.7% or abnormal detailed anatomy ultrasound would result in a 63.3% reduction in cost per each additional minor CHD diagnosed (ICER: $18,290.52 vs. $28,875.67). CONCLUSION: Fetal echocardiography appears to have limited diagnostic value in women with pregestational diabetes. However, these results may not be generalizable outside of a high-volume academic setting.