Importance:Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. Objective:To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. Design, Setting, and Participants:Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). Interventions:Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. Main Outcomes and Measures:The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. Results:Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. Conclusions and Relevance:Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age. Trial Registration:Netherlands Trial Registry Identifier: NTR6134.

IMPORTANCE Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. OBJECTIVE To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). INTERVENTIONS Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. MAIN OUTCOMES AND MEASURES The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. RESULTS Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. CONCLUSIONS AND RELEVANCE Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age.

Abstract Introduction Gestational diabetes mellitus (GDM), or hyperglycemia first diagnosed in pregnancy, affects 7–10% of all pregnancies worldwide. Perinatal risk rises with increasing glycemia at oral glucose tolerance test (OGTT). The new (2013) WHO criteria recommend a lower fasting, and a higher post-load threshold for GDM diagnosis in comparison to the old (1999) WHO criteria. To date, however, outcomes of GDM treatment for those affected by the altered diagnostic criteria, has not been well investigated. We hypothesized that intensive GDM treatment according to the new (2013) GDM criteria would result in a reduction in infants with birth weight > 90th centile (large for gestational age, LGA), in comparison to treatment according to the old criteria (1999). Methods The TANGO-DM trial is an open label, multicenter randomized controlled trial. Participants are pregnant with a gestational age between 16 + 0 and 32 + 0 weeks, who underwent a 1-step venous 2- or 3-point 75-gram oral OGTT, were eligible if they had glucose concentrations discordant between the old (1999) and the new (2013) criteria. After informed consent, women are randomized to either intensive GDM treatment, consisting of dietary advice and glucose monitoring and, if euglycemia is not reached, antihyperglycemic agents, or normal obstetric care without GDM treatment. The primary outcome is large-for-gestational-age infants (birth weight > 90th percentile). Secondary outcome measures include maternal complications, obstetric complications, neonatal complications, obstetric interventions, quality of life, and healthcare and societal costs. Outcomes will be analyzed according to the intention-to-treat principle. The study is powered to detect a reduction in LGA from 16% in the untreated to 10% in the treated group, which requires 1032 participants (516 per arm; alpha-error 5% for 80% power). Discussion The TANGO-DM trial will provide high-level evidence to support or refute the use of the new 2013 WHO diagnostic criteria in terms of their ability to lower the number of large for gestational age infants and/or improve maternal and perinatal outcomes and/or costs in women with gestational diabetes. Trial registration Central Committee on Research Involving Human Subjects (CCMO) (NL63013.018.18). Registered on 22 September 2018.

Background In the transition towards value-based healthcare, patient-reported outcome and experience measures (PROM and PREM) are recommended by international collaborations and government programs to guide clinical practice and quality improvement. For many conditions, using PROM/PREM over the complete continuum of care requires implementation across care organizations and disciplines. Along PROM/PREM implementation in obstetric care networks (OCN), we aimed to evaluate implementation outcomes and the processes influencing these outcomes in the complex context of care networks across the continuum of perinatal care. Methods Three OCN in the Netherlands implemented PROM/PREM in routine practice, using an internationally developed outcomes set with care professionals and patient advocates. Their aim was to use PROM/PREM results individually to guide patient-specific care decisions and at group-level to improve quality of care. The implementation process was designed following the principles of action research: iteratively planning implementation, action, data generation and reflection to refine subsequent actions, involving both researchers and care professionals. During the one-year implementation period in each OCN, implementation outcomes and processes were evaluated in this mixed-methods study. Data generation (including observation, surveys and focus groups) and analysis were guided by two theoretical implementation frameworks: the Normalization Process Theory and Proctor’s taxonomy for implementation outcomes. Qualitative findings were supplemented with survey data to solidify findings in a broader group of care professionals. Results Care professionals in OCN found the use of PROM/PREM acceptable and appropriate, recognized their benefits and felt facilitated in their patient-centered goals and vision. However, feasibility for daily practice was low, mainly due to IT issues and time constraints. Hence PROM/PREM implementation did not sustain, but strategies for future PROM/PREM implementation were formulated in all OCN. Processes contributing positively to implementation outcomes were internalization (understand the value) and initiation (driven by key-participants), whereas challenges in relational integration (maintain confidence) and reconfiguration (refine activities) affected implementation negatively. Conclusion Although implementation did not sustain, network-broad PROM/PREM use in clinic and quality improvement matched professionals’ motivation. This study provides recommendations to implement PROM/PREM meaningfully in practice in ways that support professionals in their drive towards patient-centered care. In order for PROM/PREM to fulfill their potential for value-based healthcare, our work highlights the need for sustainable IT infrastructures, as well as an iterative approach to refine their complex implementation into local contexts.

Aim: To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy.Materials and Methods: In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL).Results: Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes.Conclusion: In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

Abstract Introduction Vitamin D deficiency has been associated with an increased risk of cardiovascular disease (CVD) mortality in healthy populations. Whether this association is also present in patients with established CVD is not yet clear. Purpose We examined the association of serum 25-hydroxyvitamin D [25(OH)D] as an indicator of vitamin D status with 12-year risk of CVD and all-cause mortality in post-myocardial infarction (MI) patients. Methods A prospective analysis was carried out in 4,479 Dutch patients from the Alpha Omega Cohort (aged 60-80 y) who had an MI ≤10 y prior to study enrolment. Non-fasting venous blood was sampled at baseline (2002-2006) for the assessment of 25(OH)D using LC-MS/MS. Patients were followed for cause-specific mortality through December 2018. Hazard ratios (HRs) for CVD and all-cause mortality were obtained in sex-specific 25(OH)D tertiles using Cox regression models, adjusted for age, education, physical activity, smoking status, alcohol intake, adherence to dietary guidelines (i.e. 2015 Dutch Healthy Diet index [DHD15]), prevalent diabetes and kidney function (eGFR). Restricted cubic splines (RCS) analysis was performed for continuous associations, using median 25(OH)D as the reference. Results Patients were 69.0 ± 5.6 y old, 78% was male, 17% were current smokers, 18% had diabetes and 8% used vitamin-D containing supplements. A total of 2,091 deaths occurred during a median follow-up period of 12.4 y (49,529 person-years), including 924 from CVD as a primary or contributing cause. Median 25(OH)D was 21.3 ng/mL, and tertile cut-offs were 18.3 and 26.2 ng/mL for males and 15.2 and 22.0 ng/mL for females. Of the cohort, 44% were vitamin D deficient (<20 ng/mL). Lower risks of CVD mortality were observed in the mid tertile (HR: 0.76, 95%CI:0.65-0.88) and upper tertile (HR: 0.67, 95%CI:0.57-0.79) of 25(OH)D, compared to the lower tertile. RCS showed a roughly linear association (P-non-linearity = 0.08), with a 11% lower risk of CVD mortality per 5 ng/mL-increment in 25(OH)D (HR: 0.89, 95%CI: 0.86-0.93). Inverse associations were more pronounced in patients with a higher calcium intake (>845 g/d; 0.87, 95%CI:0.96-0.98; per 5 ng/mL) and in patients who were more physically active (HR: 0.88, 95%CI: 0.83-0.93; per 5 ng/mL). Exclusion of 378 vitamin D supplement users did not materially change the associations. For all-cause mortality, multivariable HRs were 0.74 (95%CI: 0.67-0.82) in the mid tertile, and 0.65 (95%CI: 0.58-0.73) in the upper tertile, compared to the lower tertile. Conclusion A low vitamin D serum concentration is related to a higher risk of recurrent CVD and all-cause mortality in patients with coronary artery disease. Causality remains to be determined preferably in a clinical trial to evaluate the effect of oral suppletion of vitamin D on recurrent CVD and mortality risk in these patients.

Introduction:Patient-reported outcome and experience measures (PROM and PREM) are used to guide individual care and quality improvement (QI). QI with patient-reported data is preferably organized around patients, which is challenging across organisations. We aimed to investigate network-broad learning for QI with outcome data.Methods:In three obstetric care networks using individual-level PROM/PREM, a learning strategy for cyclic QI based on aggregated outcome data was developed, implemented and evaluated. The strategy included clinical, patient-reported, and professional-reported data; together translated into cases for interprofessional discussion. This study's data generation (including focus groups, surveys, observations) and analysis were guided by a theoretical model for network collaboration.Results:The learning sessions identified opportunities and actions to improve quality and continuity of perinatal care. Professionals valued the data (especially patient-reported) combined with in-dept interprofessional discussion. Main challenges were professionals' time constraints, data infrastructure, and embedding improvement actions. Network-readiness for QI depended on trustful collaboration through connectivity and consensual leadership. Joint QI required information exchange and support including time and resources.Conclusions:Current fragmented healthcare organization poses barriers for network-broad QI with outcome data, but also offers opportunities for learning strategies. Furthermore, joint learning could improve collaboration to catalyse the journey towards integrated, value-based care.

AIM:We assessed the association between ethnicity and the risk of gestational diabetes mellitus (GDM) in the Netherlands. METHODS:A cohort of 7815 women with known GDM status and ethnicity, including women of Sub-Saharan African ethnicity who are currently not identified as high-risk in guidelines. We compared GDM rates among participants of ethnicity to those of ethnic Dutch participants. We employed multivariable regression to correct for possible confounders, including maternal age, pre-pregnancy body mass index (BMI), and education. GDM prevalence and odds ratios based on ethnicity were the main outcome measures. RESULTS:The prevalence rates of GDM according to ethnicity were: Dutch 0.6%, South-Asian Surinamese 6.9%, African-Surinamese 3.5%, Antillean 1.0%, Turkish 1.0%, Moroccan 1.4%, Ghanaian 6.8%, Sub-Saharan African 3.5%, other Western 0.5% and other non-Western 2.8%. After adjustment for age, pre-pregnancy BMI, and education duration, compared with the reference Dutch-ethnicity population, adjusted odds ratios (aOR) for GDM were statistically significantly higher in South-Asian Surinamese (aOR 10.9; 95% Confidence Interval (CI), 4.7-25.0), African-Surinamese (4.3; 2.0-9.2), Ghanaian (6.5; 3.0-14.5), Sub-Saharan African (5.7; 2.0-16.0), and other non-Western women (4.5; 2.2-9.0). GDM was not significantly increased among Antillean (1.4; 0.2-10.3), Turkish (1.4; 0.4-4.2), Moroccan (1.8; 0.8-4.0), and other Western women (0.8; 0.3-2.2). CONCLUSIONS:This study shows for the first time in the Netherlands that women of Ghanaian or other Sub-Saharan African ethnicity have an increased risk of developing GDM than the Dutch. This calls for adaptation of the Dutch guidelines of screening high-risk groups for GDM and more awareness amongst obstetric caregivers.

IntroductionIn women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM.MethodsThe SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals.Trial registration numberNTR6134; Pre-results.

Objective: To perform an external validation of all published prognostic models for first-trimester prediction of the risk of developing preeclampsia (PE). Methods: Women <14 weeks of pregnancy were recruited in the Netherlands. All systematically identified prognostic models for PE that contained predictors commonly available were eligible for external validation. Results: 3,736 women were included; 87 (2.3%) developed PE. Calibration was poor due to overestimation. Discrimination of 9 models for LO-PE ranged from 0.58 to 0.71 and of 9 models for all PE from 0.55 to 0.75. Conclusion: Only a few easily applicable prognostic models for all PE showed discrimination above 0.70, which is considered an acceptable performance.

AIM:Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS:We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS:Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS:In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Preterm birth is in quantity and in severity the most important contributor of perinatal morbidity and mortality both in well- and low-resource countries. Cervical pessary and cervical cerclage are both considered as preventive treatments in women at risk for preterm birth. We aim to evaluate whether a cervical pessary can replace cervical cerclage for preventing recurrent preterm birth in women with a prior preterm birth due to cervical insufficiency or in women with a prior preterm birth and a short cervix in the current pregnancy.

Objective To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy. Design External validation of all published prognostic models in large scale, prospective, multicentre cohort study. Setting 31 independent midwifery practices and six hospitals in the Netherlands. Participants Women recruited in their first trimester (<14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded. Main outcome measures Discrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots. Results 3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated. The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit. Conclusions In this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact.

OBJECTIVE: To evaluate the management of imminent preterm delivery with respect to prescription of antenatal corticosteroids (ACS) and referral to a tertiary center.STUDY DESIGN: A retrospective cohort study existing of 1 perinatal center and 9 referring hospitals. All women who received their first dose of ACS in 1 of the 10 hospitals between 24+0 and 32+0 weeks of gestation and/or delivered before 32 weeks of gestation from 2005 until 2010. Patients were identified using the electronic database of hospital pharmacies. Main outcome measures were time interval from administration to delivery for different indications and number of women who were not referred in time to a tertiary center.RESULTS: In total, 1375 women received ACS. Main indications were suspected preterm labor (44.7%), preterm prelabor rupture of membranes (15.9%), maternal indication (12.8%), fetal indication (9.2%) and vaginal blood loss (8.4%). Overall, 467 (34.0%) women delivered <= 7 days after ACS administration; 8.7% of women with vaginal blood loss and 54.5% of women with maternal indication. Among the 931 women who received ACS in the secondary hospitals, 452 (48.5%) women were referred to a tertiary hospital and 89 (6.5%) women delivered in a secondary hospital with a gestational age of less than 32 weeks.CONCLUSION: One-third of all women receiving ACS delivered within 7 days and half of the women who received ACS in a secondary hospital were referred to a tertiary center. There seems to be room for improvement regarding the timing of ACS administration and subsequently referral to a tertiary center.

Macrosomia is associated with an increased risk for both mother and child antepartum, intrapartum, as well as post-partum. We assessed the recurrence risk for macrosomia in a nationwide study in the Netherlands. Data were extracted from the Netherlands Perinatal Registry (PRN) between 1999 and 2007. A linked data set of first and second singleton deliveries was used. Data of all women who delivered their first singleton between 36 and 43 weeks of gestation were included. Fetuses with congenital malformations were excluded. Macrosomia was defined as birthweight above the 95th percentile. The recurrence risk for future macrosomia was calculated after adjustment for maternal age, interpregnancy interval, ethnicity, socio-economic status, artificial reproduction, and pre-existing diabetes. We included 247,825 women with two subsequent singleton pregnancies, of which 14,083 women (5.7%) had a macrosomic child at first delivery. Women who had a macrosomic firstborn had 29.0% risk of delivering a second macrosomic child as opposed to 4.3% risk for women without a history of macrosomia (OR 8.8, 95% CI 8.4-9.1). Induction of labour in the second pregnancy occurred in 42.3% of the patients with preceding macrosomia and in 28.3% of the pregnancies with a history of normal birthweight (OR 1.6, 95% CI 1.5-1.7). Women with a previous macrosomic child who delivered vaginally had 7.0% risk of an caesarean section of the second child, while for women without previous macrosomia who delivered vaginally this was 5.1% (OR 1.4, 95% CI 1.3-1.5). Women with a macrosomic firstborn who had a caesarean section had 59.8% risk of a repeat caesarean section, whereas women without a history of macrosomia who delivered per sectio this was 46.5% (OR 1.7, 95% CI 1.6-1.8). Women with a history of macrosomia have an increased risk of recurrent macrosomia. Furthermore, they have an increased risk of induction of labour and when they had a caesarean section they are at increased risk of a repeat caesarean section in a subsequent pregnancy.

Objective Diabetic pregnancies carry a high risk for both mother and child, especially when glycemic control is poor. A novel technique that aims to improve glycemic control is the continuous glucose monitor (CGM). This tool is already in use to improve pregnancy outcome. This review presents the available evidence on the efficacy of CGM use in pregnancy and the effectiveness on pregnancy outcome. Methods A systematic search was conducted using PubMed, EMBASE, and the Cochrane Libraries for articles on CGM in pregnancy. We evaluated the selected articles with particular attention for clinical and cost-effectiveness of CGM to improve pregnancy outcome. Results We retrieved 5032 articles, 11 of which remained as relevant after selection according to predefined criteria. Most studies were limited to the evaluation of the role of CGM on clinical decision making. Only 2 studies were randomized controlled trials (RCTs) evaluating the effect on pregnancy outcome. One small RCT on retrospective CGM showed a significant reduction in third-trimester HbA1c and a significant reduction in neonatal macrosomia. A second RCT on real-time CGM did not show any effect on either glycemic control or on pregnancy outcome. Conclusions Current evidence on the efficacy of CGM on improving glycemic control during pregnancy as well as on the effectiveness on pregnancy outcome is limited to 2 RCTs with contradicting results. Evidence on the cost-effectiveness is lacking. Further proper RCTs on the effectiveness and cost-effectiveness of CGM in pregnancy are required before wide implementation in practice. Target Audience: Obstetricians and gynecologists, family physicians and internists Learning Objectives: After completing this CME activity, physicians should be better able to compare the results of the 2 major trials on the efficacy and effectiveness of the continuous glucose monitoring system (CGM) in treating pregnant women with diabetes and evaluate the evidence on the cost-effectiveness of CGMS use in pregnant women with diabetes.

Background: Hyperglycemia in pregnancy is associated with poor perinatal outcome. Even if pregnant women with diabetes are monitored according to current guidelines, they do much worse than their normoglycaemic counterparts, marked by increased risks of pre-eclampsia, macrosomia, and caesarean section amongst others. Continuous Glucose Monitoring (CGM) is a new method providing detailed information on daily fluctuations, used to optimize glucose control. Whether this tool improves pregnancy outcome remains unclear. In the present protocol, we aim to assess the effect of CGM use in diabetic pregnancies on pregnancy outcome.Methods/design: The GlucoMOMS trial is a multicenter open label randomized clinical trial with a decision and cost-effectiveness study alongside. Pregnant women aged 18 and over with either diabetes mellitus type 1 or 2 on insulin therapy or with gestational diabetes requiring insulin therapy before 30 weeks of gestation will be asked to participate. Consenting women will be randomly allocated to either usual care or complementary CGM. All women will determine their glycaemic control by self-monitoring of blood glucose levels and HbA1c. In addition, women allocated to CGM will use it for 5-7 days every six weeks. Based on their CGM profiles they receive dietary advice and insulin therapy adjustments if necessary. The primary outcome measure is rate of macrosomia, defined as a birth weight above the 90th centile. Secondary outcome measures will be birth weight, composite neonatal morbidity, maternal outcome and costs. The analyses will be according to the intention to treat principle.Discussion: With this trial we aim at clarifying whether the CGM improves pregnancy outcome when used during diabetic pregnancies.Trial registration: Nederlands Trial Register: NTR2996