Early HbA1c Levels as a Predictor of Adverse Obstetric Outcomes: A Systematic Review and Meta-Analysis.

Background: The objective was to assess the association between early HbA1c levels and pregnancy complications and whether this relationship is affected when HbA1c thresholds are greater than or less than 39 mmol/mol (5.7%). Methods: Electronic searches of the MEDLINE and EMBASE databases up to October 2022 were conducted. We included retrospective and prospective observational studies. The inclusion criteria were as follows: HbA1c measurements taken at <20 weeks' gestation, singleton pregnancy, and no pre-existing diabetes mellitus. Results: We assessed the certainty of the evidence with the GRADE system. We determined the proportion of patients in each group who met the criteria for obstetrical outcomes and pooled data into two subgroups according to the HbA1c threshold: <39 mmol/mol or >39 mmol/mol (5.7%). Sixteen studies with a total of 43,627 women were included. An association between elevated early HbA1c levels and pre-eclampsia, large for gestational age (LGA), macrosomia, and preterm delivery (RR 2.02, 95% CI 1.53-2.66; RR 1.38, 95% CI 1.15-1.66; RR 1.40, 95% CI 1.07-1.83; and RR 1.67, 95% CI 1.39-2.0, respectively) was shown, with a moderate-high grade of certainty. According to the subgroup analysis of all studies, LGA, pre-eclampsia, and labour induction were associated with elevated HbA1c levels only in studies using an HbA1c threshold >39 mmol/mol (5.7%). The association between HbA1c levels and premature birth was statistically significant in studies using both higher and lower HbA1c thresholds. Conclusions: Women with high early HbA1c levels below the range of diabetes presented an increased risk of pregnancy complications such as macrosomia, LGA, and pre-eclampsia. An early HbA1c threshold of >39 mmol/mol (5.7%) showed the strongest association with pregnancy complications.

One abnormal value or vomiting after oral glucose tolerance test in pregnancy: incidence and impact on maternal-fetal outcomes.

OBJECTIVE: To analyze pregnancy outcomes of women with one abnormal value (OAV) during oral glucose tolerance test (OGTT) or OGTT-intolerance, compared with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnant women, according to whether they received any health intervention or not. METHODS: An observational retrospective study was designed including pregnant women who gave birth at Hospital del Mar, Barcelona (Spain) during December/2014-July/2018. Baseline characteristics, pregnancy outcomes and health interventions were obtained from a database collected previously for other study. Inclusion criteria were singleton pregnancies with OAV or OGTT-intolerants who gave birth at the Hospital. GDM screening followed a two-step approach: 50 g O'Sullivan test and 100 g 3-hour OGTT if the former was abnormal. RESULTS: From a total of 2,662 pregnancies, 326 (12.2%) had GDM, 87 OAV (3.3%), 65 OGTT intolerance (2.4%) and 2,184 were NGT women. First trimester HbA1c in both OAV and OGTT-intolerant women was significantly higher than in NGT group, and significantly lower than in GDM pregnants. No differences in obstetric outcomes were found between OGTT-intolerants and NGT/GDM groups. Treated OGTT-intolerants had greater gestational age at delivery than non-treated ones (weeks, 39.6 ± 1.2 vs 38.0 ± 4.0, respectively). In OAV women, significant differences were observed in newborns' birthweight (g, 3227.3 ± 500.8 vs 3351.1 ± 436.7, vs GDM) and gestational age at birth (weeks, 38.7 ± 1.8 vs 39.3 ± 1.9, vs NGT), but not in macrosomia/pre-eclampsia. No differences were found according to treatment in OAV. CONCLUSIONS: OAV and OGTT-intolerants account for a third of pregnant women referred to Diabetes Unit. Their rates of preterm birth, pre-eclampsia and macrosomia were not different from NGT or GDM women.

Ethnic differences in the impact of gestational diabetes on macrosomia.

BACKGROUND: Previous studies reported an ethnic disparity in gestational diabetes mellitus-associated birth outcomes, with some suggesting that macrosomia increases to a lesser extent in groups at high risk, the opposite of the pattern observed by others. Our aim was to evaluate ethnic variation in the impact of gestational diabetes mellitus (GDM). METHODS: A case-control study evaluating pregnancy outcomes was conducted in women with and without GDM from five ethnic groups. Data on GDM were collected between January 2004 and July 2017. Women giving birth between May 2013 and July 2017 in whom pre-existing diabetes had been ruled out served as controls. A multivariate logistic regression analysis was performed to determine factors independently associated with macrosomia. RESULTS: Overall, 852 GDM women and 3,803 controls were included. In Caucasian and East-Asian women excessive gestational weight gain (OR 2.273, 95% CI 1.364-3.788 and OR 3.776, 95% CI 0.958-14.886) was an independent predictor of macrosomia. In Latin-American and Moroccan women, obesity (OR 1.774, 95% CI 1.219-2.581 and OR 1.656, 95% CI 1.054-2.601), GDM (OR 2.440; 95% CI 1.048-5.679 and OR 3.249, 95% CI 1.269-8.321) and gestational weight gain but only for Latin-American women (OR 2.365, 95% CI 1.039-5.384) were associated with macrosomia. In South-Central Asian women, only GDM was associated with macrosomia (OR 3.701, 95% CI 1.437-9.532). CONCLUSIONS: GDM is an independent predictor of macrosomia in Latin-American, South-Central Asian and Moroccan women but not in Caucasian or East-Asian women in whom other factors play a more important role.

Trends in Prevalence of Diabetes among Twin Pregnancies and Perinatal Outcomes in Catalonia between 2006 and 2015: The DIAGESTCAT Study.

The aims of our study were to evaluate the trends in the prevalence of diabetes among twin pregnancies in Catalonia, Spain between 2006 and 2015, to assess the influence of diabetes on perinatal outcomes of twin gestations and to ascertain the interaction between twin pregnancies and glycaemic status. A population-based study was conducted using the Spanish Minimum Basic Data Set. Cases of gestational diabetes mellitus (GDM) and pre-existing diabetes were identified using ICD-9-CM codes. Data from 743,762 singleton and 15,956 twin deliveries between 2006 and 2015 in Catalonia was analysed. Among twin pregnancies, 1088 (6.82%) were diagnosed with GDM and 83 (0.52%) had pre-existing diabetes. The prevalence of GDM among twin pregnancies increased from 6.01% in 2006 to 8.48% in 2015 (p < 0.001) and the prevalence of pre-existing diabetes remained stable (from 0.46% to 0.27%, p = 0.416). The risk of pre-eclampsia was higher in pre-existing diabetes (15.66%, p = 0.015) and GDM (11.39%, p < 0.001) than in normoglycaemic twin pregnancies (7.55%). Pre-existing diabetes increased the risk of prematurity (69.62% vs. 51.84%, p = 0.002) and large-for-gestational-age (LGA) infants (20.9% vs. 11.6%, p = 0.001) in twin gestations. An attenuating effect on several adverse perinatal outcomes was found between twin pregnancies and the presence of GDM and pre-existing diabetes. As a result, unlike in singleton pregnancies, diabetes did not increase the risk of all perinatal outcomes in twins and the effect of pre-existing diabetes on pre-eclampsia and LGA appeared to be attenuated. In conclusion, prevalence of GDM among twin pregnancies increased over the study period. Diabetes was associated with a higher risk of pre-eclampsia, prematurity and LGA in twin gestations. However, the impact of both, pre-existing diabetes and GDM, on twin pregnancy outcomes was attenuated when compared with its impact on singleton gestations.

Trends in prevalence of pre-existing diabetes and perinatal outcomes: a large, population-based study in Catalonia, Spain, 2006-2015.

INTRODUCTION: This study aims to assess trends in the prevalence of pre-existing diabetes and whether the risk of adverse perinatal outcomes decreased in women between 2006 and 2015 in Catalonia, Spain. RESEARCH DESIGN AND METHODS: A population-based study of 743 762 singleton deliveries between 2006 and 2015 in Catalonia, Spain, was conducted using data from the Spanish Minimum Basic Data Set. Cases of type 1 diabetes (T1DM) and 'type 2 diabetes and other pre-existing diabetes' ('T2DM and other PGD') were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Crude and age-adjusted annual prevalences were calculated. Poisson regression model was used to assess trends in prevalence and perinatal outcomes during the study period. RESULTS: Overall prevalences of pre-existing diabetes, T1DM and 'T2DM and other PGD' were 0.52% (95% CI 0.51 to 0.54), 0.17% (95% CI 0.17 to 0.18) and 0.35% (95% CI 0.33 to 0.36), respectively. From 2006 to 2015, rates increased for pre-existing diabetes (from 0.43 (95% CI 0.39 to 0.48) to 0.56% (0.50 to 0.62), p<0.001), T1DM (from 0.14 (0.11 to 0.17) to 0.20% (0.17 to 0.23), p<0.001) and 'T2DM and other PGD' (from 0.29 (0.25 to 0.33) to 0.36% (0.31 to 0.40), p<0.001). Pre-eclampsia rose in women with pre-existing diabetes (from 4.38% to 8.97%, adjusted p<0.001), T1DM (from 3.85% to 12.88%, p=0.005) and 'T2DM and other PGD' (from 4.63% to 6.78%, adjusted p=0.01). Prevalence of prematurity, cesarean section and small for gestational age remained stable in all diabetes groups. However, the prevalence of macrosomia fell in women with pre-existing diabetes (from 18.18% to 11.9%, adjusted p=0.011) and 'T2DM and other PGD' (from 14.71% to 11.06%, non-adjusted p=0.022, adjusted p=0.305) and large for gestational age decreased in all diabetes groups (from 39.73% to 30.25% in pre-existing diabetes, adjusted p=0.004). CONCLUSIONS: The prevalence of pre-existing diabetes increased significantly in Catalonia between 2006 and 2015. Despite improvements in outcomes related to excessive birth weight, pre-eclampsia rates are rising and overall perinatal outcomes in women with pre-existing diabetes continue to be markedly worse than in the population without diabetes.

Trends in prevalence of gestational diabetes and perinatal outcomes in Catalonia, Spain, 2006 to 2015: the Diagestcat Study.

BACKGROUND: No recent epidemiologic studies on gestational diabetes mellitus (GDM) have been conducted in Spain. The present study aimed to explore trends in the prevalence of GDM and ascertain whether the risk of adverse perinatal outcomes changed between 2006 and 2015 in Catalonia. METHODS: In this population-based study, all hospital admissions for singleton births in Catalonia for the period 2006 to 2015 were collected from the Spanish Minimum Basic Data Set. Cases of GDM were identified from hospital delivery discharge reports using ICD-9-CM codes. Data regarding maternal characteristics and perinatal outcomes were analysed. Crude and age-adjusted annual prevalences were calculated. The Poisson regression model was used to assess trends in prevalence and perinatal outcomes, adjusted for age and smoking habit; however, they could not be adjusted for body mass index (BMI) and ethnicity. RESULTS: Data from 743 762 deliveries were collected. GDM prevalence over the study period was 4.80% (95% CI 4.75-4.85%). Crude GDM prevalence rose from 3.81% (95% CI 3.67-3.95%) in 2006 to 6.53% (95% CI 6.33-6.72%) in 2015 (P < 0.001). Women with GDM showed a stable trend in rates of preeclampsia (2.56%), prematurity (15.7%), and large-for-gestational age (LGA) newborns (18.3%), whereas a lower rate of macrosomia was observed during the study period (from 9.16% to 7.84%). Caesarean deliveries rose from 28% to 31%; however, significance was lost after adjustment. CONCLUSIONS: The prevalence of GDM in Catalonia almost doubled between 2006 and 2015. During the study period, the frequency of macrosomia decreased whereas pre-eclampsia, prematurity, LGA, and age-adjusted Caesarean rates remained stable.

Association of first-trimester HbA1c levels with adverse pregnancy outcomes in different ethnic groups.

AIM: To determine, in a multi-ethnic cohort, the association of first-trimester HbA1c levels with the development of pregnancy complications. METHODS: A prospective study between April 2013-October 2016. Participants were stratified in five ethnic groups. Women had an HbA1c measurement added to their first antenatal bloods. Primary outcome was macrosomia and secondary outcomes included preeclampsia and large-for-gestational age (LGA). A multivariate logistic regression analysis was performed to adjust for potential confounders in determining the association between different HbA1c cut-off points and obstetric outcomes on each ethnic group. RESULTS: 1,882 pregnancies were included. Analysis was limited to the three main ethnic groups: Caucasian (54.3%), South-Central Asian (19%) and Latin-American (12.2%). There was no association between HbA1c levels and obstetric outcomes among Caucasians. In Latin-Americans, an HbA1c ≥ 5.8% (40 mmol/mol) was associated with higher risk of macrosomia, whereas an HbA1c ≥ 5.9% (41 mmol/mol) was associated with LGA. In South-Central Asian, an HbA1c ≥ 5.7% (39 mmol/mol) was associated with increased risk of macrosomia and a continuous graded relationship between HbA1c levels and preeclampsia and LGA was detected starting at HbA1c levels of 5.4% (36 mmol/mol). CONCLUSION: First-trimester HbA1c levels perform as a suitable predictor of pregnancy complications in South-Central Asian and Latin-American women whereas in Caucasian no significant associations were found.

Is fasting plasma glucose in early pregnancy a better predictor of adverse obstetric outcomes than glycated haemoglobin?

OBJECTIVES: To determine, in a multi-ethnic cohort, the suitability of first-trimester fasting plasma glucose and HbA1c levels in non-diabetic range to identify women without diabetes at increased pregnancy risk. STUDY DESIGN: A retrospective analysis of a prospective cohort between April 2013 and September 2015. Universal testing for fasting plasma glucose and HbA1c levels at the first antenatal blood sampling was performed and women were screened for gestational diabetes mellitus at 24-28 weeks' gestation. Primary outcomes were macrosomia and pre-eclampsia, and secondary outcomes preterm delivery, Caesarean section and large-for-gestational age. Different fasting plasma glucose and HbA1c cut-off levels were assessed for associations with outcomes. RESULTS: 1,228 pregnancies were included for outcome analysis. After adjustment for potential confounders, no association was found between fasting plasma glucose levels and pregnancy outcomes. Women with an HbA1c ≥5.8% (39.9 mmol/mol) showed an increased risk of macrosomia (OR 2.69, 95% CI 1.16-6.24); an HbA1c ≥5.9% (41 mmol/mol) threshold was independently associated with a three-fold risk of pre-eclampsia (95% CI 1.03-9.9) and an HbA1c ≥6.0% (42.1 mmol/mol) with a four-fold risk of large-for-gestational age (95% CI 1.49-11.07). CONCLUSIONS: In a multi-ethnic population, first-trimester fasting plasma glucose levels were not a better predictor of pregnancy complications than HbA1c. Further, an early HbA1c ≥5.8% (39.9 mmol/mol) threshold is already associated with an increased risk of macrosomia.

Impact of overt diabetes diagnosed in pregnancy in a multi-ethnic cohort in Spain.

Overt diabetes (ODM) is defined as women without diabetes meeting the criteria for diabetes at the first antenatal visit. The risk of obstetric complications increases linearly with maternal glycemia and poorer maternal-fetal outcomes than in gestational diabetes (GDM) may be expected. Studies focusing on ODM pregnancy outcomes are lacking. We aimed to analyze maternal characteristics and pregnancy outcomes in ODM women compared with those with GDM. A retrospective cohort study of women giving birth between January 2010 and April 2013 was conducted. Participants with pre-gestational diabetes were excluded. All women underwent screening for GDM at the 24th-28th weeks of gestation or at the first prenatal visit in those with risk factors. HbA1c and a fasting glucose were measured in GDM women to rule out ODM. Of the 5,633 women included, 572 (10%) were diagnosed with GDM and 50 (0.88%) with ODM. Almost 95% of ODM women were from ethnic minorities. After adjustment for confounding factors, ODM women showed increased rates of premature birth (23.1% vs. 6.7%, p < .001), emergent cesarean section (41.0% vs. 19.5%, p = .049), preeclampsia (22% vs. 3.7%, p < .001) and large-for-gestational-age babies (40.0% vs. 14.8%, p = .008) compared with GDM. In conclusion, ODM is associated with poorer obstetric outcomes than GDM and affects mainly women from ethnic minorities.

Is first-trimester HbA1c useful in the diagnosis of gestational diabetes?

AIMS: To evaluate the usefulness and efficacy of first-trimester HbA1c in the diagnosis of gestational diabetes (GDM). METHODS: Prospective observational of consecutive pregnant women. All women had a first-trimester HbA1c determination and GDM screening at 24-28weeks of pregnancy using a two-step approach. A ROC curve was drawn to determine the sensitivity and specificity of HbA1c in detecting GDM and a rule-in rule-out diagnostic algorithm was proposed. The cost of the proposed algorithm was calculated. RESULTS: 152 (13.1%) of 1195 women were diagnosed of GDM. The area under the ROC curve for HbA1c to detect GDM was 0.679 (95%CI 0.631-0.727). A rule-out threshold for HbA1c of 4.8% (29mmol/mol) had 96.7% sensitivity (95%CI 93.9-99.5), 10.1% specificity (95%CI 8.3-12.0) and a negative predictive value of 95.3% (95%CI 91.3-99.3). A rule-in value of 5.6% (38mmol/mol) had a positive predictive value of 31.6% (95%CI 24.4-38.9), 89.3% specificity (95%CI 87.4-91.2) and 32.9% sensitivity (95%CI 25.4-40.4). The low positive predictive value of the rule-in threshold precludes its use for GDM diagnosis, but could be used to identify women at high risk of GDM in whom the diagnosis can be established using a one-step approach. The overall saving of the proposed algorithm would be 6.5% of the total cost with the standard strategy. CONCLUSIONS: A first-trimester HbA1c does not have sufficient sensitivity or specificity to diagnose GDM, although the use of a higher and lower threshold could simplify the diagnostic process by reducing the number of oral glucose tolerance test, associated costs and patient inconvenience.

Role of First-Trimester HbA1c as a Predictor of Adverse Obstetric Outcomes in a Multiethnic Cohort.

Context: Risk of obstetric complications increases linearly with rising maternal glycemia. Testing hemoglobin A1c (HbA1c) is an effective option to detect hyperglycemia, but its association with adverse pregnancy outcomes remains unclear. Emerging data sustain that an early HbA1c ≥5.9% could act as a pregnancy risk marker. Objective: To determine, in a multiethnic cohort, whether an early ≥5.9% HbA1c could be useful to identify women without diabetes mellitus at increased pregnancy risk. Design and Setting: A prospective study was conducted at Hospital del Mar, Barcelona, between April 2013 and September 2015. Patients and Intervention: A total of 1631 pregnant women had an HbA1c measurement added to their first antenatal blood tests and were screened for gestational diabetes mellitus at 24 to 28 weeks' gestation. Outcome Measures: Primary outcome was macrosomia. Secondary outcomes were preeclampsia, preterm birth, and cesarean section rate. Results: A total of 1228 pregnancies were included for outcome analysis. Women with HbA1c ≥5.9% (n = 48) showed a higher rate of macrosomia (16.7% vs 5.9%, P = 0.008) and a tendency toward a higher rate of preeclampsia (9.32% vs 3.9%, P = 0.092). There were no statistically significant differences in other pregnancy outcomes. After adjusting for potential confounders, an HbA1c ≥5.9% was independently associated with a 3-fold increased risk of macrosomia (95% confidence interval, 1.127 to 8.603, P = 0.028) and preeclampsia (95% confidence interval, 1.086 to 11.532, P = 0.036). Conclusions: In a multiethnic population, an early HbA1c ≥5.9% measurement identifies women at high risk for poorer pregnancy outcomes independently of gestational diabetes mellitus diagnosis later in pregnancy. Further studies are required to establish cutoff points adapted to each ethnic group and to assess whether early detection and treatment are of benefit.