Glycemic control assessed by continuous glucose monitoring during pregnancy in women with type 1 diabetes and its association with preeclampsia, an observational Swedish cohort study.

INTRODUCTION: Women with type 1 diabetes have an increased risk of preeclampsia (PE), but it is not fully understood if degree of glycemic control is associated with this risk. The aim of this study was to assess glycemic control during pregnancy analyzed by continuous glucose monitoring (CGM) in women with and without PE and to investigate if glycemic control is associated with increased risk of PE. MATERIAL AND METHODS: A total of 120 pregnant Swedish women with type 1 diabetes using CGM were included. Background factors and pregnancy outcomes were collected from medical records. CGM data were collected via the internet-based platform Diasend. Mean glucose, standard deviation of mean glucose, percentage of time in target, time below target, and time above target were presented for each trimester in women who did or did not develop PE. Associations between CGM-derived metrics and PE were analyzed with logistic regression and adjusted for confounders. RESULTS: Twenty-two women (18.3%) developed PE. There were no significant differences in maternal characteristics between women with and without PE. Glycemic control improved in each trimester but was suboptimal in both groups. Time in target increased from 59% in the non-PE group and 54% in the PE group in the first trimester to 65% in both groups in the third trimester. There were no significant associations between glycemic control and PE after adjustment for confounders. CONCLUSIONS: Degree of glycemic control during pregnancy assessed by CGM was not associated with development of PE in women with type 1 diabetes. However, more research is needed to understand the role of glycemic control in relation to development of PE.

Continuous Glucose Monitoring Metrics and Birth Weight: Informing Management of Type 1 Diabetes Throughout Pregnancy.

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.

Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy - Pump vs multiple daily injections, a secondary analysis of an observational cohort study.

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.

Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort.

Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 µg/kg) above the spline knot of 0.50 µg/kg was associated with reduced birth weight (B: -191 g; 95% CI: -315, -68) and length (-0.67 cm; -1.2, -0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 µg/kg, mainly MeHg) above 1.0 µg/kg, was associated with decreased birth weight (-59 g; -115, -3.0), and length (-0.29 cm; -0.54, -0.047). Maternal Pb (median 11 µg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.

Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages.

INTRODUCTION: There is an increasing prevalence of non-communicable diseases worldwide. Metabolic diseases such as obesity and gestational diabetes mellitus (GDM) increasingly affect women during pregnancy, which can harm pregnancy outcomes and the long-term health and wellbeing of exposed offspring. Both obesity and GDM have been associated with proinflammatory effects within the placenta, the critical organ governing fetal development. METHODS: The purpose of these studies was to model, in vitro, the effects of metabolic stress (high levels of glucose, insulin and saturated lipids) on placental macrophage biology, since these cells are the primary innate immune phagocyte within the placenta with roles in governing maternofetal immune tolerance and antimicrobial host defense. Macrophages were isolated from the villous core of term, human placentae delivered through nonlaboring, elective Cesarean sections and exposed to combinations of elevated glucose (30 mM), insulin (10 nM) and the saturated lipid palmitic acid (palmitate, 0.4 mM). RESULTS: We found that palmitate alone induced the activation of the nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in placental macrophages, which was associated with increased interleukin 1 beta release and an increase in apoptotic cell death. Glucose and insulin neither provoked these effects nor augmented the impact of palmitate itself. DISCUSSION: Our findings confirm an impact of saturated fat on placental macrophage immune activation and could be relevant to the impact of metabolic stress in vivo.

Associations between maternal dietary patterns and infant birth weight, small and large for gestational age in the Norwegian Mother and Child Cohort Study.

BACKGROUND/OBJECTIVES: To assess whether quality of maternal diet affects birth weight and the risk of small for gestational age (SGA) and/or large for gestational age (LGA) babies. SUBJECTS/METHODS: This study is based on the Norwegian Mother and Child Cohort Study (MoBa) and includes 65,904 pregnant women who answered a validated food frequency questionnaire at mid-pregnancy. Three maternal dietary patterns were extracted based on characteristics of food items in each pattern. From these we created four non-overlapping groups: "high prudent," "high Western," "high traditional," and "mixed". We obtained information about birth weight from the Norwegian Medical Birth Registry and calculated birth weight z-scores, SGA, and LGA according to an ultrasound-based, population-based, and a customized growth standards. Associations were studied by linear and multiple logistic regression. RESULTS: Compared to the high Western group, the high prudent group was associated with lower birth weight (ßultrasound z-scores -0.041 (95% confidence interval (CI): -0.068, -0.013)) and the high traditional group with higher birth weight (ßultrasound 0.067 (95% CI: 0.040, 0.094)) for all three growth standards. The high prudent pattern was associated with increased SGA risk (SGAultrasound odds ratio (OR) 1.25 (95% CI: 1.02, 1.54)) and decreased LGA risk (LGApopulation OR 0.84 (95% CI: 0.75, 0.94)), while the high traditional group on the contrary was associated with decreased SGA (SGAcustomized OR 0.92 (95% CI: 0.84, 0.99)) and increased LGA risk (LGApopulation OR 1.12 (95% CI: 1.02, 1.24)). CONCLUSIONS: Food quality was associated with birth weight in this well-nourished Norwegian population. Food quality may affect a woman's risk of giving birth to a SGA or LGA baby.

Meal frequency patterns and glycemic properties of maternal diet in relation to preterm delivery: Results from a large prospective cohort study.

BACKGROUND: Dietary habits are linked to high maternal glucose levels, associated with preterm delivery. The aim of this study was to examine the associations between meal frequency and glycemic properties of maternal diet in relation to preterm delivery. METHODS: This prospective cohort study included 66,000 women from the Norwegian Mother and Child Cohort Study (MoBa). Meal frequency and food intake data were obtained from a validated food frequency questionnaire during mid-pregnancy. Principal component factor analysis was used with a data-driven approach, and three meal frequency patterns were identified: "snack meal", "main meal", and "evening meal". Pattern scores were ranked in quartiles. Glycemic index and glycemic load were estimated from table values. Intakes of carbohydrates, added sugar, and fiber were reported in grams per day and divided into quartiles. Gestational age was obtained from the Medical Birth Registry of Norway. Preterm delivery was defined as birth at <37 gestational weeks. A Cox regression model was used to assess associations with preterm delivery. RESULTS: After adjustments, the "main meal" pattern was associated with a reduced risk of preterm delivery, with hazard ratios (HRs) of 0.89 (95% confidence interval (CI): 0.80, 0.98) and 0.90 (95% CI: 0.81, 0.99) for the third and fourth quartiles, respectively, and p for trend of 0.028. This was mainly attributed to the group of women with BMI ≥25 kg/m2, with HRs of 0.87 (95% CI: 0.79, 0.96) and 0.89 (95% CI: 0.80, 0.98) for the third and fourth quartiles, respectively, and p for trend of 0.010. There was no association between glycemic index, glycemic load, carbohydrates, added sugar, fiber, or the remaining meal frequency patterns and preterm delivery. CONCLUSION: Regular consumption of main meals (breakfast, lunch, dinner) was associated with a lower risk of preterm delivery. Diet should be further studied as potential contributing factors for preterm delivery.

Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery.

BACKGROUND: Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. METHODS: The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. RESULTS: Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (>5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0.85) for ≥3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. CONCLUSIONS: Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.

Maternal dietary patterns and preterm delivery: results from large prospective cohort study.

OBJECTIVE: To examine whether an association exists between maternal dietary patterns and risk of preterm delivery. DESIGN: Prospective cohort study. SETTING: Norway, between 2002 and 2008. PARTICIPANTS: 66 000 pregnant women (singletons, answered food frequency questionnaire, no missing information about parity or previously preterm delivery, pregnancy duration between 22+0 and 41+6 gestational weeks, no diabetes, first enrolment pregnancy). MAIN OUTCOME MEASURE: Hazard ratio for preterm delivery according to level of adherence to three distinct dietary patterns interpreted as "prudent" (for example, vegetables, fruits, oils, water as beverage, whole grain cereals, fibre rich bread), "Western" (salty and sweet snacks, white bread, desserts, processed meat products), and "traditional" (potatoes, fish). RESULTS: After adjustment for covariates, high scores on the "prudent" pattern were associated with significantly reduced risk of preterm delivery hazard ratio for the highest versus the lowest third (0.88, 95% confidence interval 0.80 to 0.97). The prudent pattern was also associated with a significantly lower risk of late and spontaneous preterm delivery. No independent association with preterm delivery was found for the "Western" pattern. The "traditional" pattern was associated with reduced risk of preterm delivery for the highest versus the lowest third (hazard ratio 0.91, 0.83 to 0.99). CONCLUSION: This study showed that women adhering to a "prudent" or a "traditional" dietary pattern during pregnancy were at lower risk of preterm delivery compared with other women. Although these findings cannot establish causality, they support dietary advice to pregnant women to eat a balanced diet including vegetables, fruit, whole grains, and fish and to drink water. Our results indicate that increasing the intake of foods associated with a prudent dietary pattern is more important than totally excluding processed food, fast food, junk food, and snacks.

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study.

BACKGROUND: Artificially sweetened (AS) and sugar-sweetened (SS) beverages are commonly consumed during pregnancy. A recent Danish study reported that the daily intake of an AS beverage was associated with an increased risk of preterm delivery. OBJECTIVE: We examined the intake of AS and SS beverages in pregnant women to replicate the Danish study and observe whether AS intake is indeed associated with preterm delivery. DESIGN: This was a prospective study of 60,761 pregnant women in the Norwegian Mother and Child Cohort Study. Intakes of carbonated and noncarbonated AS and SS beverages and use of artificial sweeteners in hot drinks were assessed by a self-reported food-frequency questionnaire in midpregnancy. Preterm delivery was the primary outcome, and data were obtained from the Norwegian Medical Birth Registry. RESULTS: Intakes of both AS and SS beverages increased with increasing BMI and energy intake and were higher in women with less education, in daily smokers, and in single women. A high intake of AS beverages was associated with preterm delivery; the adjusted OR for those drinking >1 serving/d was 1.11 (95% CI: 1.00, 1.24). Drinking >1 serving of SS beverages per day was also associated with an increased risk of preterm delivery (adjusted OR: 1.25; 95% CI: 1.08, 1.45). The trend tests were positive for both beverage types. CONCLUSION: This study suggests that a high intake of both AS and SS beverages is associated with an increased risk of preterm delivery.

Alcohol consumption in relation to metabolic regulation, inflammation, and adiponectin in 64-year-old Caucasian women: a population-based study with a focus on impaired glucose regulation.

OBJECTIVE: The aims of this study were to examine alcohol drinking patterns in women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) and to investigate whether alcohol intake was associated with improved insulin sensitivity, decreased biomarkers of inflammation, and increased adiponectin levels and if these effects were limited to dysmetabolic women. RESEARCH DESIGN AND METHODS: From a cohort of 64-year-old Caucasian women, 209 with type 2 diabetes, 205 with IGT, and 186 with NGT were recruited. Alcohol consumption and medication use were assessed by questionnaires. Anthropometric data were collected, and blood glucose, insulin, HDL cholesterol, triglycerides, C-reactive protein, white blood cell count, and serum adiponectin were measured. RESULTS: Compared with the NGT group, alcohol consumption was lower in the IGT group and lowest in the diabetes group. Mean alcohol intakes of >9.2 and > or =3-9 g/day were positively associated with adiponectin and insulin sensitivity (homeostasis model assessment [HOMA]), respectively, independently of obesity, metabolic control, and other confounders. Alcohol intake correlated negatively with inflammatory markers, although this did not remain after adjustment for HOMA and waist circumference. The inverse associations between alcohol consumption and factors related to the metabolic syndrome such as HOMA, waist circumference, and inflammatory markers were more obvious among women with diabetes and IGT than in healthy women. CONCLUSIONS: In these women, moderate alcohol consumption showed beneficial associations with the prevalence of type 2 diabetes, IGT, insulin sensitivity, and serum adiponectin. There is a need to clarify whether adiponectin may be a mechanistic link and also to clarify the clinical implications of these observations.