Karl Kristensen

Introduction: Self‐monitoring of blood glucose (SMBG) is the standard of care for women with gestational diabetes mellitus (GDM). This study aimed to review SMBG profiles in women with GDM and to examine how glucose metrics derived from SMBG relate to fetal overgrowth and infants born large for gestational age (LGA, >90th percentile).Material and Methods: This was a single‐center, historical, observational cohort study of 879 GDM pregnancies in Sweden. The diagnosis of GDM was based on a universal 75 g oral glucose tolerance test at gestational week 28 or 12 in high‐risk women. The glucose metrics derived from the SMBG profiles were calculated. Treatment targets for glucose were p < 0.001). The corresponding discriminating thresholds were 5.3 and 6.1 mmol/L, respectively. Mean glucose levels increased and readings in target decreased with increasing body mass index category and at each step of adding pharmacological treatment, from diet alone to metformin and insulin (p < 0.001).Conclusions: Higher mean glucose levels and a smaller proportion of readings within the target range were associated with an increased risk of LGA. Suboptimal glucose control is associated with obesity and the need for pharmacological treatment.

OBJECTIVE: To determine gestational weekly changes in continuous glucose monitoring (CGM) metrics and 24-h glucose profiles and their relationship to infant birth weight in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: An analysis of >10.5 million CGM glucose measures from 386 pregnant women with type 1 diabetes from two international multicenter studies was performed. CGM glucose metrics and 24-h glucose profiles were calculated for each gestational week, and the relationship to normal (10–90th percentile) and large (>90th percentile) for gestational age (LGA) birth weight infants was determined. RESULTS: Mean CGM glucose concentration fell and percentage of time spent in the pregnancy target range of 3.5–7.8 mmol/L (63–140 mg/dL) increased in the first 10 weeks of pregnancy and plateaued until 28 weeks of gestation, before further improvement in mean glucose and percentage of time in range until delivery. Maternal CGM glucose metrics diverged at 10 weeks of gestation, with significantly lower mean CGM glucose concentration (7.1 mmol/L; 95% CI 7.05–7.15 [127.8 mg/dL; 95% CI 126.9–128.7] vs. 7.5 mmol/L; 95% CI 7.45–7.55 [135 mg/dL; 95% CI 134.1–135.9]) and higher percentage of time in range (55%; 95% CI 54–56 vs. 50%; 95% CI 49–51) in women who had normal versus LGA. The 24-h glucose profiles were significantly higher across the day from 10 weeks of gestation in LGA. CONCLUSIONS: Normal birth weight is associated with achieving significantly lower mean CGM glucose concentration across the 24-h day and higher CGM time in range from before the end of the first trimester, emphasizing the need for a shift in clinical management, with increased focus on using weekly CGM glucose targets for optimizing maternal glycemia from early pregnancy.

Introduction: Continuous glucose monitoring (CGM) provides detailed information about glucose level fluctuations over time. The method is increasingly being used in pregnant women with type 1 diabetes. However, only one previous study compared CGM results related to pregnancy outcomes in women using insulin pumps with those administering multiple daily injections (MDI). We performed a secondary analysis of CGM metrics from an observational cohort of pregnant women with type 1 diabetes and compared insulin pump and MDI therapies in relation to maternal and neonatal outcomes.Material and methods: The study included 185 pregnant Swedish women with type 1 diabetes undergoing CGM throughout pregnancy. Women were divided according to insulin administration mode, ie MDI (n = 131) or pump (n = 54). A total of 91 women used real‐time CGM and 94 women used intermittently viewed CGM. Maternal demographics and maternal and neonatal outcome data were collected from medical records. CGM data were analyzed according to predefined glycemic indices: mean glucose; standard deviation; percentage of time within, below and above glucose target range; mean amplitude of glycemic excursion; high and low glucose indices; and coefficient variation in percent. Associations between insulin administration mode and CGM data, on the one hand, and maternal and neonatal outcomes, on the other, were analyzed with analysis of covariance and logistic regression, respectively, adjusted for confounders.Results: There were no differences in maternal characteristics or glycemic indices between the MDI and pump groups, except for a longer duration of type 1 diabetes and higher frequencies of microangiopathy and real‐time CGM among pump users. Despite improvement with each trimester, glucose levels remained suboptimal throughout pregnancy in both groups. There were no differences between the MDI and pump groups concerning the respective associations with any of the outcomes. The frequency of large for gestational age was high in both groups (MDI 49% vs pump 63%) and did not differ significantly.Conclusions: Pregnant women with type 1 diabetes did not differ in glycemic control or pregnancy outcome, related to MDI or pump administration of insulin. Glycemic control remained suboptimal throughout pregnancy, regardless of insulin administration mode.

Introduction: Obstetricians routinely use biochemical parameters from non‐pregnant women to assess the condition of the laboring mother. However, it is well known that pregnancy leads to significant physiological changes in most organ systems. The aim of this study was to determine normal values for maternal arterial blood gases during vaginal deliveries as compared with control values from planned cesarean sections. We also wanted to elucidate the effect of various maternal characteristics, mode of delivery and obstetric interventions on blood gas values.Material and methods: We carried out a randomly selected, prospective‐observational cohort study of 250 women undergoing vaginal delivery and 58 women undergoing planned cesarean section at the Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden.Results: We found significant differences for gestational age, parity, umbilical venous blood pH, pCO₂ and lactate values between the two study groups (P < .005). Significantly lower pH, pCO₂, pO₂ and sO₂ were found in mothers delivering vaginally. Higher base deficit, hemoglobin, bilirubin, potassium, glucose and lactate were found in vaginal deliveries than in planned cesarean sections (P < .02). Maternal body mass index (BMI), smoking and hypertension were not significantly correlated to acid base parameters in women with vaginal deliveries. On the other hand, multiple regression showed significant associations for the use of epidural anesthesia on maternal pH (P < .05) and pO₂ (P < .01); and synthetic oxytocin on pCO₂ (P = .08), glucose (P < .00) and lactate (P < .02) levels in maternal arterial blood. Maternal arterial pH, pCO₂ and lactate values correlated significantly to values in venous umbilical cord blood (P < .000).Conclusions: Maternal arterial blood gas parameters varied significantly according to mode of delivery, the use of epidural anesthesia and synthetic oxytocin.

Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM). We have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1–2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum. After adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567–6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = −5.478, 95% CI: -8.315 to −2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = −6.319, 95% CI: −9.466 to −3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes. This study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results.

Objective: To determine a reference interval for maternal arterial blood values during vaginal delivery and to elucidate the effect of common maternal characteristics and obstetric interventions on maternal acid base values during vaginal and planned cesarean section (CS). Design: Prospective, observational study of randomly selected women undergoing vaginal deliveries and planned CS at Skåne University Hospital, Malmö, Sweden. Results: Two hundred and fifty women undergoing vaginal delivery (VD) and fifty-eight women undergoing planned CS were recruited. We found significant differences for gestational age, parity, artery pH, pCO ₂ , pO ₂ , sO ₂ and cord venous pH, pCO ₂ and lactate between the two study groups ( P < 0.005). For women undergoing vaginal delivery, we found significant changes in base deficit, hemoglobin, bilirubin, potassium, glucose and lactate values as compared to women with planned CS ( P < 0.02). Maternal characteristics did not significantly affect acid base parameters however, multiple regression showed significant associations for the use of epidural anesthesia on maternal pH ( P < 0.05) and pO ₂ ( P < 0.01); and synthetic oxytocin on pCO ₂ ( P = 0.08), glucose ( P < 0.00) and lactate ( P < 0.02) in maternal blood. Maternal arterial pH, pCO ₂ and lactate correlated significantly to values in venous umbilical cord blood ( P < 0.000). Conclusions: Reference values for maternal arterial blood gases in vaginal deliveries for term pregnancies were outlined and we found that most arterial blood gas parameters varied significantly according to mode of delivery. The use of different obstetrical interventions like epidural anesthesia or synthetic oxytocin, resulted in significant changes in blood gas values.

Aims/hypothesis The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes. Methods This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5–7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders. Results The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target. Conclusions/interpretation Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.

Introduction: An antenatal corticosteroid (ACS) delivery interval of 24 h to seven days is commonly referred to as optimal timing. We aimed to investigate whether the ACS delivery interval was associated with the obstetric indication for treatment and with neonatal complications.Material and methods: The study was a retrospective chart review of clinical data from preterm neonates delivered at the Skåne University Hospital, Lund University, Sweden, from 1 January 2013 to 31 December 2016. The ACS delivery intervals were compared between groups of women with various clinical scenarios and related to neonatal outcomes.Results: The study included 498 preterm neonates from 431 women. One to seven days before delivery, 41% of the women received ACS. Women with preterm prelabor rupture of membranes or vaginal bleeding had a median ACS delivery interval of 7.5 and eight days, respectively, compared with women with maternal/fetal indications or preterm labor (three and two days, respectively) (p < 0.001). Neonates with an ACS delivery interval of more than seven days were at a higher risk of respiratory distress syndrome [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.05–3.79] and moderate or severe bronchopulmonary dysplasia (OR 2.78, 95% CI 1.45–5.33) than were neonates with an ACS delivery interval of one to seven days.Conclusion: Optimal timing of ACS treatment varied significantly based on the clinical indication. Women with preterm prelabor rupture of membranes or vaginal bleeding were more likely to have an ACS delivery interval of more than seven days. A prolonged ACS delivery interval was associated with an increased risk of neonatal respiratory morbidity and a prolonged stay in the neonatal care unit, but not with neonatal mortality.

Despite improved glycemic control, the rate of large-for-gestational-age (LGA) infants remains high in pregnancies complicated by diabetes mellitus type 1 (T1DM) and type 2 (T2DM). Poor glycemic control, obesity, and excessive gestational weight gain are the main risk factors. The aim of this study was to determine the relative contribution of these risk factors for LGA in women with T1DM and T2DM, after controlling for important confounders such as age, smoking, and parity. In this retrospective chart review study, we analyzed the medical files of pregnant women with T1DM and T2DM who attended the antenatal care program at Skåne University Hospital during the years 2006 to 2016. HbA1c was used as a measure of glycemic control. Maternal weight in early pregnancy and at term was registered. LGA was defined as birth weight > 2 standard deviations of the mean. Univariable and multivariable logistic regression analysis was used to calculate odds ratios (OR’s) and 95% confidence intervals (CIs) for LGA. Over the 11-year period, we identified 308 singleton pregnancies in 221 women with T1DM and in 87 women with T2DM. The rate of LGA was 50% in women with T1DM and 23% in women with T2DM. The multivariable regression model identified gestational weight gain and second-trimester HbA1c as risk factors for LGA in T1DM pregnancies (OR = 1.107, 95% CI: 1.044–1.17, and OR = 1.047, 95% CI: 1.015–1.080, respectively) and gestational weight gain as a risk factor in T2DM pregnancies (OR = 1.175, 95% CI: 1.048–1.318), independent of body mass index. Gestational weight gain was associated with LGA in women with T1DM and T2DM, independent of maternal body mass index. The findings suggest that monitoring and regulation of gestational weight gain is important in the clinical care of these women, to minimize the risk of fetal overgrowth.