The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Use of a pocket-sized ultrasound machine (PUM) for routine examinations in the third trimester of pregnancy.

OBJECTIVES: To evaluate the application of a pocket-sized ultrasound machine (PUM) in a routine antenatal third-trimester scan compared with a high-specification ultrasound machine (HSUM). METHODS: This was an observational cohort study of 53 unselected women who came for their routine third-trimester ultrasound scan. The first scan was performed by an experienced ultrasonographer on an HSUM for fetal growth, fetal wellbeing and placental location. A second experienced operator performed the measurements on the PUM. Both operators were blinded to the other's findings and measurement results. RESULTS: Fifty-one patients were eligible and scanned at a median gestational age of 31 + 1 (range, 27 + 2 to 36 + 0) weeks. Mean pregestational body mass index was 22.9 ± 3.1 (range, 17.6-35.7) kg/m(2) . In the comparison between measurements made using the PUM and HSUM, perfect agreement was found for fetal position, fetal bladder and stomach visualization (all κ 1.0) and very good agreement was found for placental position (κ 0.86). Measurements of deepest vertical pocket correlated moderately (intraclass correlation coefficient (ICC) 0.38 (95% CI, 0.12-0.59); Bland-Altman bias, 2.43 (95% limits of agreement (LoA), -22.65 to 27.51)). For fetal growth measurements there was very good agreement for biparietal diameter (ICC, 0.93 (95% CI, 0.88-0.96), Bland-Altman bias, -1.06 (95% LoA, -5.07 to 2.95)), and good agreement for femur length (ICC, 0.66 (95% CI, 0.48-0.79), Bland-Altman bias 0.56 (95% LoA, -5.97 to 7.08)) and transcerebellar diameter (ICC, 0.65 (95% CI, 0.46-0.78), Bland-Altman bias, -0.84 (95% LoA, -7.77 to 6.09)). CONCLUSION: A battery-driven PUM can be used in third-trimester obstetrics for routine assessment of fetal growth (biparietal diameter, transcerebellar diameter and femur length) and for assessment of fetal wellbeing.

Partial monochorionic and monoamniotic twin pregnancies: a report of two cases.

Monochorionic (MC) twin pregnancies are at increased risk of adverse outcome because of the vascular anastomoses that connect the two fetal circulations. MC monoamniotic (MA) twins are at an even higher risk because of their almost universal cord entanglement and possible compression, which can cause an acute transfusion imbalance between the twins. Chorionicity and amnionicity should be determined during the first-trimester ultrasound examination to identify high-risk MC and MA twin pregnancies for which a fortnightly follow-up may improve outcome. Although this can be achieved readily by assessing and counting the membranes that separate the twins, some pitfalls may occur. We present our observations of two monozygotic twin pairs with an intermediate type of monodichorionic and monodiamniotic twin pregnancy. The first was recognized during the first-trimester scan and the second during the second-trimester scan.

Gestational age-specific reference ranges for amniotic fluid assessment in monochorionic diamniotic twin pregnancies.

OBJECTIVES: To establish gestational age-specific reference ranges for amniotic fluid measurements in monochorionic diamniotic twin pregnancies, to compare them with previously reported singleton and twin reference ranges and to examine the rationale for using a gestational age-dependent cut-off to define polyhydramnios in twin-twin transfusion syndrome, as is the practice in most European centers. METHODS: We retrospectively evaluated amniotic fluid volume in 32 monochorionic diamniotic twin pregnancies that were followed longitudinally at 2-week intervals from the first trimester until birth. Amniotic fluid volume was assessed by measuring the deepest vertical pocket in both amniotic sacs. We used multilevel modeling to estimate the gestational age-specific reference ranges for deepest vertical pocket measurements. RESULTS: Based on 429 observations in 64 fetuses, we constructed gestational age-specific reference ranges from 11 weeks until term. The deepest pocket increased from the first trimester to reach a maximum at 26 weeks, followed by a gradual decrease towards term. Measurements between 18 and 28 weeks were comparable to those in singleton pregnancies. However, before 18 weeks values were higher, whereas after 28 weeks they were lower, as compared to singleton references. CONCLUSION: In monochorionic twin pregnancies, the deepest vertical pocket is a gestational age-dependent measurement. Therefore, a gestational age-dependent definition of polyhydramnios in twin-twin transfusion syndrome, as used by most European centers, seems a logical approach.

The influence of weight gain patterns in pregnancy on fetal growth using cluster analysis in an obese and nonobese population.

OBJECTIVE: Excessive weight gain during pregnancy has an important influence on fetal growth and on weight development in future generations. DESIGN AND METHODS: A prospective cohort study of 325 obese and nonobese Caucasian women with naturally conceived, singleton pregnancies was performed. They were followed up until delivery for maternal weight gain and for fetal growth with ultrasound-based weight estimations and final birth weight. Using cluster analysis distinct profiles of maternal weight gain during pregnancy were obtained. Longitudinal regression analysis was performed to investigate the relationship of the maternal weight gain profile and BMI on fetal growth and final birth weight. RESULTS: Cluster analysis revealed four discernable maternal weight gain profiles: 12 cases (3.7%) ended up at their starting weight or decreased in weight (cluster 1), 16 cases (4.9%) who slightly increased in weight (maximum 4 kg) as compared to their initial weight (cluster 2), 114 cases (35.1%) who gained between 4 and 12 kg in weight (cluster 3), and 183 cases (56.3%) who showed the largest weight gain: more than 12 kg (cluster 4). There were statistically significant differences in fetal growth associated with weight gain cluster, which became apparent late in the second trimester and increased toward the end of pregnancy. Maternal BMI and maternal weight gain profile were independent predictors of fetal growth and birth weight. CONCLUSIONS: Therefore, the conclusion is that the cluster analysis permits to discern four gestational weight gain (GWG) patterns in obese and nonobese subjects and that both maternal BMI and maternal weight gain pattern during pregnancy positively influence fetal growth and birth weight.

Analysis of the cell infiltrate and expression of matrix metalloproteinases and granzyme B in paired synovial biopsy specimens from the cartilage-pannus junction in patients with RA.

OBJECTIVES: Examination of synovial tissue (ST) obtained at surgery because of end stage destructive rheumatoid arthritis (RA) showed that macrophages and fibroblasts are the major cell types at the cartilage-pannus junction (CPJ). This study aimed at defining the cell infiltrate and mediators of joint destruction in ST selected at arthroscopy from the CPJ in patients with RA who did not require joint surgery. METHODS: Paired synovial biopsy specimens were obtained at arthroscopy from ST adjacent to the CPJ and the suprapatellar pouch from the knee joints of 17 patients with RA. Immunohistological analysis was performed using monoclonal antibodies to detect T cells, B cells, plasma cells, macrophages, fibroblast-like synoviocytes, mast cells, and granzyme B+ cytotoxic cells as well as the expression of metalloproteinase (MMP)-1, MMP-3, and MMP-13. The sections were evaluated by computer assisted image analysis and semiquantitative analysis. RESULTS: The cell infiltrate comprised mainly T cells, macrophages, and plasma cells. The ST was also infiltrated by the other cell types, but at lower numbers. Expression of MMPs was abundant, especially MMP-3. The features of ST at the CPJ were generally similar to those at the suprapatellar pouch. CONCLUSIONS: The synovium at the CPJ in patients with RA who did not require joint surgery exhibits, in general, the same type of cell infiltrate and expression of MMPs and granzymes as ST from the suprapatellar pouch. The pathological changes that have been described at the CPJ in patients with RA with end stage, destructive disease may well reflect the transition to a process in which macrophages, fibroblast-like synoviocytes, and other cell types become increasingly important.