Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes: A post-hoc analysis of the GlucoMOMS trial.

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.

Quality Improvement with Outcome Data in Integrated Obstetric Care Networks: Evaluating Collaboration and Learning Across Organizational Boundaries with an Action Research Approach.

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.

PROMs and PREMs in routine perinatal care: mixed methods evaluation of their implementation into integrated obstetric care networks.

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.

External validation of prognostic models for preeclampsia in a Dutch multicenter prospective cohort.

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.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

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.

Serum concentrations of psychotropic drugs in neonates as a PROgnOstic Factor for admission to the neonatology ward and withdrawal symptoms: PROOF-1.

The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.

External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study.

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.

Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels.

OBJECTIVE: The primary aim of this study was to investigate the correlation between pregnancy outcome and bile acid (BA) levels in pregnancies that were affected by intrahepatic cholestasis of pregnancy (ICP). In addition, correlations between maternal and fetal BA levels were explored. STUDY DESIGN: We conducted a retrospective study that included women with pruritus and BA levels ≥10 µmol/L between January 2005 and August 2012 in 3 large hospitals in the Netherlands. The study group was divided in mild (10-39 µmol/L), moderate (40-99 µmol/L), and severe (≥100 µmol/L) ICP. Main outcome measures were spontaneous preterm birth, meconium-stained amniotic fluid, asphyxia, and perinatal death. Univariate and multivariate logistic regression analysis was used to study associations between BA levels and adverse outcome. RESULTS: A total of 215 women were included. Gestational age at diagnosis and gestational age at delivery were significantly lower in the severe, as compared with the mild, ICP group (P < .001). Spontaneous preterm birth (19.0%), meconium-stained fluid (47.6%), and perinatal death (9.5%) occurred significantly more often in cases with severe ICP. Higher BA levels were associated significantly with spontaneous preterm birth (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 1.03-1.28), meconium-stained amniotic fluid (aOR, 1.15; 95% CI, 1.06-1.25), and perinatal death (aOR, 1.26; 95% CI, 1.01-1.57). Maternal BA levels at diagnosis and at delivery were correlated positively with umbilical cord blood BA levels (P = .006 and .012, respectively). CONCLUSION: Severe ICP is associated with adverse pregnancy outcome. Levels of BA correlate between mother and fetus.

Evaluation of strategies regarding management of imminent preterm delivery before 32 weeks of gestation: a regional cohort study among 1375 women in the Netherlands.

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.

The efficacy and effectiveness of continuous glucose monitoring during pregnancy: a systematic review.

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.

Effectiveness of continuous glucose monitoring during diabetic pregnancy (GlucoMOMS trial); a randomised controlled trial.

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.

Cardiac function in 7-8-year-old offspring of women with type 1 diabetes.

Offspring of type 1 diabetic mothers (ODMs) are at risk of short-term and long-term complications, such as neonatal macrosomia (birth weight >90th percentile), hypertrophic cardiomyopathy, and cardiovascular morbidity in later life. However, no studies have been performed regarding cardiac outcome. In this study, we investigated cardiac dimensions and function in 30 ODMs at 7-8 years of age in relation to neonatal macrosomia and maternal glycemic control during pregnancy and compared these with those in a control group of 30 children of nondiabetic women. We found that cardiac dimensions and systolic and diastolic function parameters in ODMs were comparable with those in controls. Neonatal macrosomia and poorer maternal glycemic control during pregnancy were not related to worse cardiac outcome in ODM. We conclude that cardiac function at 7-8 years of age in offspring of women with type 1 diabetes is reassuring and comparable with that in controls.

[Gestational diabetes mellitus: treatment reduces the risk of complications]. / Diabetes gravidarum. Behandeling vermindert kans op complicaties.

Recent studies show that higher blood glucose values after a 75 g oral glucose tolerance test in pregnancy are associated with higher rates of perinatal and maternal complications. Treatment of gestational diabetes mellitus (hyperglycaemia in pregnancy) reduces the risk of complications. Gestational diabetes mellitus is an asymptomatic condition. Screening is the only strategy for diagnosing this disorder of pregnancy in time, in order to provide treatment. Until recently, there was no uniformity concerning diagnostic strategy and treatment of gestational diabetes mellitus in the Netherlands, possibly due to lack of evidence on the risk of complications and the effectiveness of treatment. Results of several recent studies show that early detection and treatment of gestational diabetes mellitus are effective. By means of a more active screening and treatment policy it should be possible to reduce the perinatal and maternal complications as a result of gestational diabetes mellitus.

Cardiovascular and metabolic outcome in 6-8 year old offspring of women with type 1 diabetes with near-optimal glycaemic control during pregnancy.

BACKGROUND: High maternal glucose concentrations during diabetic pregnancy may lead to health problems in the offspring later in life. We showed in a previous nationwide study on pregnancy outcome in type 1 diabetic women that prepregnancy care was good and a near-optimal glycaemic control during pregnancy was achieved (mean HbA1c 6.2%). AIMS: We investigated to what extent current care and treatment of pregnant women with type 1 diabetes were related to cardiovascular and metabolic disturbances in the offspring at school age. Additionally, we studied the influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia (birth weight>p 90). STUDY DESIGN: Observational cohort study. SUBJECTS: 6-8 year old offspring of women with type 1 diabetes (ODM, n=213) and a control group of children of non-diabetic women (n=79). OUTCOME MEASURES: BMI, blood pressure, parameters of fasting glucose regulation and lipid metabolism, components of the metabolic syndrome (overweight, hypertension, impaired fasting glucose, dyslipidaemia). RESULTS: Parameters of fasting glucose regulation and lipid metabolism and the frequency of components of the metabolic syndrome did not significantly differ between ODM and controls. Systolic blood pressure was slightly higher in ODM. The influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia on outcome in ODM was limited. CONCLUSIONS: Current care and treatment of pregnant women with type 1 diabetes result in cardiovascular and metabolic outcome in the offspring at 6-8 years of age that is comparable to that in children of non-diabetic women. Further follow-up should substantiate these results at later age.

Risk factors for childhood overweight in offspring of type 1 diabetic women with adequate glycemic control during pregnancy: Nationwide follow-up study in the Netherlands.

OBJECTIVE: Pregnancy in type 1 diabetic women remains a high-risk situation for both mother and child. In this study, we investigated long-term effects on body composition, prevalence of overweight, and insulin resistance in children of type 1 diabetic women who had had adequate glycemic control during pregnancy (mean A1C 6.2%), and we related their outcome to perinatal factors, including macrosomia (birth weight >90th percentile). RESEARCH DESIGN AND METHODS: Anthropometric measurements were performed at 6-8 years of age in 213 offspring of type 1 diabetic mothers who participated in a previous nationwide study. Homeostasis model assessment of insulin resistance (HOMA-IR) was determined from a fasting blood sample in 155 of these children. In addition, we studied BMI standard deviation score (SDS) growth trajectories. Results were compared with national reference data. RESULTS: The prevalence of overweight in the study population was not different from that in the reference population. However, children who were born macrosomic showed twice as much overweight as nonmacrosomic children. Macrosomia and maternal overweight were independent predictors of childhood overweight. Overweight children showed an increase in BMI SDS starting already after 6 months of age and had a significantly increased HOMA-IR. CONCLUSIONS: In type 1 diabetic women with adequate glycemic control during pregnancy, long-term effects on body composition and overweight in their offspring at school age are limited and related mainly to macrosomia at birth. Possible targets for prevention of childhood overweight are fetal macrosomia, maternal overweight, and an increase in BMI SDS during the first years of life.

Male predominance of congenital malformations in infants of women with type 1 diabetes.

OBJECTIVE: To investigate sex-related differences in maternal, perinatal, and neonatal outcome in type 1 diabetic pregnancies in the Netherlands. RESEARCH DESIGN AND METHODS: This was a nationwide prospective cohort-based study. Logistic regression analysis was used to identify sex-specific risk factors for adverse pregnancy outcome. RESULTS: A total of 323 type 1 diabetic pregnancies were included; 314 were ongoing after 24 weeks of gestation. There were eight twin pregnancies and one triplet, resulting in 324 infants born after 24 weeks of gestation. Multiple logistic regression analysis showed that the occurrence of congenital malformations was independently associated with male newborns (OR 3.5 [95% CI 1.3-10.0]; P = 0.02). CONCLUSIONS: The higher incidence of congenital malformations in infants of women with type 1 diabetes appears to be restricted to male infants only.

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

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

Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences.

There is strong evidence that the avoidance of hyperglycemia is essential inoptimizing pregnancy outcome in type 1 diabetes. The price to pay is a striking increase in severe hypoglycemia (SH), defined as episodes requiring help from another person. During type 1 diabetic pregnancy, occurrence rates of SH up to 15 times higher as in the intensively treated group of the Diabetes Control and Complications Trial (DCCT) are reported. Blood glucose (BG) treatment targets differ considerably between clinics; some authors advocate lower limits as low as 3.3 mmol/l. Improved glycemic control and/or recurrent hypoglycemia (i.e. BG <3.9 mmol/l) may result in impairment of glucose counterregulatory responses. Also, glucose counterregulation may be altered by pregnancy itself. Short-acting insulin analogs may help reduce hypoglycemia with preservation of good glycemic control, but their use during pregnancy has yet to be proven safe.Several clinical studies did not establish an association between maternal hypoglycemia and diabetic embryopathy. However, animal studies clearly indicate that hypoglycemia is potentially teratogenic during organogenesis. Increased rates of macrosomia continue to be observed despite near normal HbA(1c) levels. This may, at least in part, be the result of rebound hyperglycemia elicited by hypoglycemia. Exposure to hypoglycemia in utero may have long-term effects on offspring including neuropsychological defects. It is yet unclear to what extent the benefits of tight glycemic control balance with the increased risk of (severe) hypoglycemia during type 1 diabetic pregnancy. Efforts must be made to avoid low BG, i.e. <3.9 mmol/l, when tightening glycemic control.

Risk indicators predictive for severe hypoglycemia during the first trimester of type 1 diabetic pregnancy.

OBJECTIVES: To investigate the frequency of severe hypoglycemia (SH) and hypoglycemic coma during the first trimester of type 1 diabetic pregnancy and in the 4 months before gestation and to identify risk indicators predicting first trimester SH in a nonselected nationwide cohort of pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a longitudinal cohort survey in 278 pregnant type 1 diabetic women using questionnaires at inclusion and at 17 weeks of gestation, addressing the frequencies of SH (i.e., external help required) and hypoglycemic coma, general characteristics, hypoglycemia awareness, blood glucose symptom threshold, and the Hypoglycemia Fear Survey. RESULTS: The occurrence of SH (including hypoglycemic coma) rose from 0.9 +/- 2.4 episodes per 4 months before gestation to 2.6 +/- 6.3 episodes during the first trimester (P < 0.001), including an increase in episodes of coma from 0.3 +/- 1.3 to 0.7 +/- 3.7 (P=0.03). The proportion of women affected by SH rose from 25 to 41% (P < 0.001). First-trimester SH was independently related to a history of SH before gestation (odds ratio [95%CI]: 9.2 [3.9-21.7]), a 10 years' longer diabetes duration (1.6 [1.0-2.4]), an HbA1c level < or = 6.5% (2.5 [1.3-5.0]), and a 0.1 unit/kg higher daily insulin dose (5.4 [1.5-18.9]), adjusted for a decreased symptom threshold. CONCLUSIONS: In type 1 diabetic pregnancy, the risk of SH is increased already before pregnancy and rises further during the first trimester. A history of SH before gestation, longer duration of diabetes, an HbA1c level < or = 6.5%, and a higher total daily insulin dose were risk indicators predictive for SH during the first trimester. Further research should aim to elucidate how the benefits of strict glycemic control balance with the markedly increased risk of SH early in pregnancy.