Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight.

AIMS/HYPOTHESIS: It is not known whether the early-pregnancy metabolome differs in patients with early- vs late-onset gestational diabetes mellitus (GDM) stratified by maternal overweight. The aims of this study were to analyse correlations between early-pregnancy metabolites and maternal glycaemic and anthropometric characteristics, and to identify early-pregnancy metabolomic alterations that characterise lean women (BMI <25 kg/m2) and women with overweight (BMI ≥25 kg/m2) with early-onset GDM (E-GDM) or late-onset GDM (L-GDM). METHODS: We performed a nested case-control study within the population-based prospective Early Diagnosis of Diabetes in Pregnancy cohort, comprising 210 participants with GDM (126 early-onset, 84 late-onset) and 209 normoglycaemic control participants matched according to maternal age, BMI class and primiparity. Maternal weight, height and waist circumference were measured at 8-14 weeks' gestation. A 2 h 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and women with normal results underwent repeat testing at 24-28 weeks' gestation (OGTT2). Comprehensive metabolomic profiling of fasting serum samples, collected at OGTT1, was performed by untargeted ultra-HPLC-MS. Linear models were applied to study correlations between early-pregnancy metabolites and maternal glucose concentrations during OGTT1, fasting insulin, HOMA-IR, BMI and waist circumference. Early-pregnancy metabolomic features for GDM subtypes (participants stratified by maternal overweight and gestational timepoint at GDM onset) were studied using linear and multivariate models. The false discovery rate was controlled using the Benjamini-Hochberg method. RESULTS: In the total cohort (n=419), the clearest correlation patterns were observed between (1) maternal glucose concentrations and long-chain fatty acids and medium- and long-chain acylcarnitines; (2) maternal BMI and/or waist circumference and long-chain fatty acids, medium- and long-chain acylcarnitines, phospholipids, and aromatic and branched-chain amino acids; and (3) HOMA-IR and/or fasting insulin and L-tyrosine, certain long-chain fatty acids and phospholipids (q<0.001). Univariate analyses of GDM subtypes revealed significant differences (q<0.05) for seven non-glucose metabolites only in overweight women with E-GDM compared with control participants: linolenic acid, oleic acid, docosapentaenoic acid, docosatetraenoic acid and lysophosphatidylcholine 20:4/0:0 abundances were higher, whereas levels of specific phosphatidylcholines (P-16:0/18:2 and 15:0/18:2) were lower. However, multivariate analyses exploring the early-pregnancy metabolome of GDM subtypes showed differential clustering of acylcarnitines and long-chain fatty acids between normal-weight and overweight women with E- and L-GDM. CONCLUSIONS/INTERPRETATION: GDM subtypes show distinct early-pregnancy metabolomic features that correlate with maternal glycaemic and anthropometric characteristics. The patterns identified suggest early-pregnancy disturbances of maternal lipid metabolism, with most alterations observed in overweight women with E-GDM. Our findings highlight the importance of maternal adiposity as the primary target for prevention and treatment.

Impact of smoking on gestational diabetes mellitus and offspring birthweight in primiparous women.

INTRODUCTION: Smoking has been shown to affect glucose homeostasis and increase the risk for type 2 diabetes mellitus. Further, gestational diabetes mellitus (GDM) and smoking are known to influence offspring birthweight. The effect of smoking on glucose homeostasis in pregnancy is less studied and the findings are inconsistent. The aim of this study was to evaluate the effect of smoking on risk for GDM and to evaluate the impact of smoking and GDM on offspring birthweight. MATERIAL AND METHODS: This is an observational cohort study encompassing 4111 Finnish primiparous women from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data were obtained from Finnish national registers. Study participants had complete oral glucose tolerance test results and were divided into three groups according to smoking status: non-smokers (I), smokers who quit during first trimester (II), and smokers who continued after first trimester (III). RESULTS: Prevalence of GDM was 19.8%, 24.3%, and 26.6% in non-smokers, those who quit, and those who continued after the first trimester, respectively (P = .004 for differences between groups). The odds ratio for GDM in smokers who continued after the first trimester compared with non-smokers was 1.65 (95% CI 1.09-2.57) after adjustments for age, prepregnancy body mass index, education, and cohabitation. In women without GDM, offspring birthweight was lowest in those who continued smoking after the first trimester (P = .010 for differences between groups). In women with GDM, smoking status did not influence offspring birthweight. CONCLUSIONS: Smoking during pregnancy is associated with an increased risk for GDM. Offspring birthweight is lowest in women who continue smoking after the first trimester. If pregnancy is complicated by GDM, offspring birthweight is not influenced by smoking.

The impact of educational attainment on the occurrence of gestational diabetes mellitus in two successive pregnancies of Finnish primiparous women: a population-based cohort study.

AIMS: To assess the impact of educational attainment on the occurrence and recurrence of gestational diabetes mellitus (GDM) in two successive pregnancies in primiparous women. METHODS: This is a population-based observational cohort study including all 2347 Finnish women without previously diagnosed diabetes, aged ≥ 20 years from the city of Vantaa, Finland, who gave birth to their first and second child between 2009 and 2015. National registries provided data on study participants. We divided the population into four groups according to the presence of GDM in the two pregnancies (GDM-/-, n = 1820; GDM-/+, n = 223; GDM+/-, n = 113; GDM+/+, n = 191). RESULTS: The occurrence of GDM in the first pregnancy was 13.0% (n = 304) and 17.6% (n = 414) in the second. The recurrence rate of GDM was 62.8%. The four groups did not differ in relation to educational attainment (p = 0.11). In multinomial regression analysis, educational attainment protected from GDM in the second pregnancy [relative risk ratio 0.93 (95% confidence interval (CI) 0.86-0.99) per year of schooling for being GDM-/+ compared with GDM-/-]. In multivariate logistics models, prepregnancy body mass index at the first pregnancy [odds ratio (OR) 1.53 per 1-standard deviation (SD) (95% CI 1.22-1.91)], first-born birth weight z-score [OR 1.30 per 1-SD (95% CI 1.00-1.67)], and inter-pregnancy weight change [OR 1.66 per 1-SD (95% CI 1.27-2.16)], but not educational attainment, predicted recurrence of GDM. CONCLUSIONS: The recurrence rate of GDM was high. Education protected from novel GDM in the second pregnancy, but was not associated with GDM recurrence.

Impact of maternal height and gestational diabetes mellitus on offspring birthweight.

AIMS: To evaluate the impact of gestational diabetes mellitus (GDM) and maternal height on offspring birthweight. METHODS: This is an observational cohort study, encompassing 4 111 Finnish primiparous women from Vantaa city, Finland, with singleton deliveries between 2009 and 2015. Data were obtained from the Finnish Medical Birth Register. The study population was divided into five groups according to maternal height. Cut-offs for height levels were I ≤ 158 cm, II 159-163 cm, III 164-167 cm, IV 168-172 cm, V ≥ 173 cm. The main outcome measure was offspring birthweight, expressed as Z-scores according to sex and gestational age. RESULTS: Independently, both maternal height and GDM increased offspring birthweight (p < 0.001 for height and GDM). When studying the interaction, a significant increase in offspring birthweight was noted only in extreme height categories; group I ≤ 158 cm (p = 0.011), group IV 168-172 cm (p = 0.010) and group V ≥ 173 cm (p < 0.001) and the impact was similar in both sexes. Maternal height had no impact on offspring ponderal index (p = 0.20 for trend). CONCLUSIONS: In extreme height categories, short and tall primiparous women with GDM are at risk for delivering larger offspring compared to women without GDM of similar height.

Body surface area at birth and later risk for gestational diabetes mellitus among primiparous women.

AIMS: To assess the relationship between body surface area (BSA) at birth and future risk for gestational diabetes mellitus (GDM). METHODS: This is an observational cohort study from Vantaa, Finland. The cohort included 1548 Finnish primiparous women, aged 15-28 years, without pre-existing diabetes, who gave birth 2009-2015. All women were born full-term and had complete information about their birth weight and length, from the Finnish Medical Birth Register. Additional data for the study were provided by individual patient health records and Statistics Finland. Study participants were divided into five levels (I-V) according to BSA at birth, based on normal distribution. RESULTS: There was an inverse association between BSA at birth and risk for GDM (p = 0.015 for linearity, after adjustments for age, educational attainment, pre-pregnancy BMI and smoking). The odds ratio (OR) for GDM in level V, with the largest BSA at birth, compared with level I, with the smallest BSA at birth, was 0.43 [95% confidence interval (CI) 0.22-0.83]; adjusted for age, educational attainment, pre-pregnancy body mass index and smoking. The OR for GDM was 0.8 (95% CI 0.68-0.95, p = 0.009) for each one standard deviation increase in BSA at birth, adjusted for the same confounders. BSA at birth correlated with adult anthropometry: correlation coefficients were r = 0.16 (95% CI 0.11-0.21) for weight, r = 0.31 (95% CI 0.26-0.35) for height, and r = 0.06 (95% CI 0.01-0.11) for BMI. CONCLUSIONS: Body surface area at birth is inversely associated with future risk for GDM in primiparous women.

Risk of preterm birth in primiparous women with exposure to antidepressant medication before pregnancy and/or during pregnancy - impact of body mass index.

INTRODUCTION: Preterm birth is a major cause of infant mortality. It is unknown whether body mass index (BMI) influences the risk of preterm birth in women, who prenatally use antidepressants. MATERIALS AND METHODS: The study cohort (N = 6920) consists of all primiparous European born women without previously diagnosed diabetes from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data on births, pre-pregnancy BMI and purchases of antidepressants from 12 months before conception until delivery were obtained from Finnish National Registers. RESULTS: Of the primiparous women, 9.9% used antidepressants. The overall prevalence of preterm birth was 5.2%. In women with a pre-pregnancy BMI <18.5 kg/m2, the Odds Ratio (OR) for preterm birth among antidepressant users compared with those who were non-users was 1.91 (95% confidence intervals [CI] 0.40 to 9.15, adjusted for age, smoking, education, use of fertility treatments and number of previous pregnancies) while in women with a pre-pregnancy BMI ≥30 kg/m2, the OR was 0.53 (95% CI 0.21-1.36), respectively. DISCUSSION: Primiparous women using antidepressants, who were underweight before conception should be closely monitored and provided tailored care in a maternity clinic to minimize the risk of preterm birth. Key messages In primiparous women, one in ten used antidepressant medications before pregnancy and/or during pregnancy. In primiparous women, the prevalence of preterm birth was 5%. Underweight primiparous women using antidepressants should be closely monitored and provided tailored care in a maternity clinic.