Incidence and risk factors for hyperglycemia in pregnancy among nulliparous women: A Brazilian multicenter cohort study.

OBJECTIVE: To assess the incidence and risk factors for hyperglycemia in pregnancy in a cohort of Brazilian nulliparous pregnant women. MATERIALS AND METHODS: This is a secondary analysis of a multicenter cohort study that enrolled 1,008 nulliparous pregnant women at 19-21 weeks. Exclusion criteria included chronic exposure to corticosteroids and previous diabetes. Bivariate and multivariate analyses by Poisson regression were used to identify associated factors. RESULTS: The incidence of hyperglycemia in pregnancy was 14.9% (150/1,008), and 94.7% of these cases were gestational diabetes mellitus (142/150). Significant associated factors included a family history of diabetes mellitus, maternal overweight or obesity at enrollment, and previous maternal conditions (polycystic ovarian syndrome, thyroid dysfunctions and hypertensive disorders). A BMI ≥ 26.3Kg/m2 (RRadj 1.87 [1.66-2.10]) and a family history of diabetes mellitus (RRadj 1.71 [1.37-2.15]) at enrollment were independent risk factors for HIP. CONCLUSIONS: A family history of diabetes mellitus and overweight or obesity (until 19-21 weeks of gestation) may be used as selective markers for HIP in Brazilian nulliparous women. Given the scarcity of results in nulliparous women, our findings may contribute to determine the optimal diagnostic approach in populations of similar socioeconomic characteristics.

Trace biomarkers associated with spontaneous preterm birth from the maternal serum metabolome of asymptomatic nulliparous women - parallel case-control studies from the SCOPE cohort.

Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.

Examining the predictive accuracy of metabolomics for small-for-gestational-age babies: a systematic review.

INTRODUCTION: To date, there is no robust enough test to predict small-for-gestational-age (SGA) infants, who are at increased lifelong risk of morbidity and mortality. OBJECTIVE: To determine the accuracy of metabolomics in predicting SGA babies and elucidate which metabolites are predictive of this condition. DATA SOURCES: Two independent researchers explored 11 electronic databases and grey literature in February 2018 and November 2018, covering publications from 1998 to 2018. Both researchers performed data extraction and quality assessment independently. A third researcher resolved discrepancies. STUDY ELIGIBILITY CRITERIA: Cohort or nested case-control studies were included which investigated pregnant women and performed metabolomics analysis to evaluate SGA infants. The primary outcome was birth weight <10th centile-as a surrogate for fetal growth restriction-by population-based or customised charts. STUDY APPRAISAL AND SYNTHESIS METHODS: Two independent researchers extracted data on study design, obstetric variables and sampling, metabolomics technique, chemical class of metabolites, and prediction accuracy measures. Authors were contacted to provide additional data when necessary. RESULTS: A total of 9181 references were retrieved. Of these, 273 were duplicate, 8760 were removed by title or abstract, and 133 were excluded by full-text content. Thus, 15 studies were included. Only two studies used the fifth centile as a cut-off, and most reports sampled second-trimester pregnant women. Liquid chromatography coupled to mass spectrometry was the most common metabolomics approach. Untargeted studies in the second trimester provided the largest number of predictive metabolites, using maternal blood or hair. Fatty acids, phosphosphingolipids and amino acids were the most prevalent predictive chemical subclasses. CONCLUSIONS AND IMPLICATIONS: Significant heterogeneity of participant characteristics and methods employed among studies precluded a meta-analysis. Compounds related to lipid metabolism should be validated up to the second trimester in different settings. PROSPERO REGISTRATION NUMBER: CRD42018089985.

Clamping the Umbilical Cord in Premature Deliveries (CUPiD): Neuromonitoring in the Immediate Newborn Period in a Randomized, Controlled Trial of Preterm Infants Born at <32 Weeks of Gestation.

OBJECTIVE: To compare cerebral activity and oxygenation in preterm infants (<32 weeks of gestation) randomized to different cord clamping strategies. STUDY DESIGN: Preterm infants born at <32 weeks of gestation were randomized to immediate cord clamping, umbilical cord milking (cord stripped 3 times), or delayed cord clamping for 60 seconds with bedside resuscitation. All infants underwent electroencephalogram (EEG) and cerebral near infrared spectroscopy for the first 72 hours after birth. Neonatal primary outcome measures were quantitative measures of the EEG (17 features) and near infrared spectroscopy over 1-hour time frames at 6 and 12 hours of life. RESULTS: Forty-five infants were recruited during the study period. Twelve infants (27%) were randomized to immediate cord clamping, 19 (42%) to umbilical cord milking, and 14 (31%) to delayed cord clamping with bedside resuscitation. There were no significant differences between groups for measures of EEG activity or cerebral near infrared spectroscopy. Three of the 45 infants (6.7%) were diagnosed with severe IVH (2 in the immediate cord clamping group, 1 in the umbilical cord milking group; P = .35). CONCLUSIONS: There were no differences in cerebral EEG activity and cerebral oxygenation values between cord management strategies at 6 and 12 hours. TRIAL REGISTRATION: ISRCTN92719670.

Planning, Implementing, and Running a Multicentre Preterm Birth Study with Biobank Resources in Brazil: The Preterm SAMBA Study.

BACKGROUND: Our aim was to describe the steps in planning, implementing, and running a multicentre cohort study of maternal and perinatal health using a high-quality biobank comprised of maternal serum, plasma, and hair samples collected from five sites in Brazil. The Preterm SAMBA study, conducted by the Brazilian Network for Studies on Reproductive and Perinatal Health, was an innovative approach used to identify women at higher risk for preterm birth. It is also of great importance in the study of other maternal and perinatal complications in the context of Brazil, which is a middle-income country. METHODS: We described phases of planning, implementing, and running the Preterm SAMBA study, a multicentre Brazilian cohort study of low-risk nulliparous pregnant women, to validate a set of metabolite biomarkers for preterm birth identified in an external cohort. Procedures and strategies used to plan, implement, and maintain this multicentre preterm birth study are described in detail. Barriers and experience cited in the current narrative are not usually discussed in the scientific literature or published study protocols. RESULTS: Several barriers and strategies were identified in different phases of the Preterm SAMBA study at different levels of the study framework (steering committee; coordinating and local centres). Strategies implemented and resources used in the study are a legacy of the Brazilian Network, aimed at training collaborators in such complex settings. CONCLUSION: The Brazilian Network for Studies on Reproductive and Perinatal Health has gained some experience in conducting a multicentre cohort study using a resourceful biobank which may be helpful to other research groups and maternal/perinatal health networks that plan on employing a similar approach to a similar background.

Metabolomics for predicting fetal growth restriction: protocol for a systematic review and meta-analysis.

INTRODUCTION: Fetal growth restriction (FGR) is a relevant research and clinical concern since it is related to higher risks of adverse outcomes at any period of life. Current predictive tools in pregnancy (clinical factors, ultrasound scan, placenta-related biomarkers) fail to identify the true growth-restricted fetus. However, technologies based on metabolomics have generated interesting findings and seem promising. In this systematic review, we will address diagnostic accuracy of metabolomics analyses in predicting FGR. METHODS AND ANALYSIS: Our primary outcome is small for gestational age infant, as a surrogate for FGR, defined as birth weight below the 10th centile by customised or population-based curves for gestational age. A detailed systematic literature search will be carried in electronic databases and conference abstracts, using the keywords 'fetal growth retardation', 'metabolomics', 'pregnancy' and 'screening' (and their variations). We will include original peer-reviewed articles published from 1998 to 2018, involving pregnancies of fetuses without congenital malformations; sample collection must have been performed before clinical recognition of growth impairment. If additional information is required, authors will be contacted. Reviews, case reports, cross-sectional studies, non-human research and commentaries papers will be excluded. Sample characteristics and the diagnostic accuracy data will be retrieved and analysed. If data allows, we will perform a meta-analysis. ETHICS AND DISSEMINATION: As this is a systematic review, no ethical approval is necessary. This protocol will be publicised in our institutional websites and results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018089985.

Use of metabolomics for the identification and validation of clinical biomarkers for preterm birth: Preterm SAMBA.

BACKGROUND: Spontaneous preterm birth is a complex syndrome with multiple pathways interactions determining its occurrence, including genetic, immunological, physiologic, biochemical and environmental factors. Despite great worldwide efforts in preterm birth prevention, there are no recent effective therapeutic strategies able to decrease spontaneous preterm birth rates or their consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate metabolomics technologies to identify clinical and metabolite predictors for preterm birth. These innovative and unbiased techniques might be a strategic key to advance spontaneous preterm birth prediction. METHODS/DESIGN: Preterm SAMBA study consists of a discovery phase to identify biophysical and untargeted metabolomics from blood and hair samples associated with preterm birth, plus a validation phase to evaluate the performance of the predictive modelling. The first phase, a case-control study, will randomly select 100 women who had a spontaneous preterm birth (before 37 weeks) and 100 women who had term birth in the Cork Ireland and Auckland New Zealand cohorts within the SCOPE study, an international consortium aimed to identify potential metabolomic predictors using biophysical data and blood samples collected at 20 weeks of gestation. The validation phase will recruit 1150 Brazilian pregnant women from five participant centres and will collect blood and hair samples at 20 weeks of gestation to evaluate the performance of the algorithm model (sensitivity, specificity, predictive values and likelihood ratios) in predicting spontaneous preterm birth (before 34 weeks, with a secondary analysis of delivery before 37 weeks). DISCUSSION: The Preterm SAMBA study intends to step forward on preterm birth prediction using metabolomics techniques, and accurate protocols for sample collection among multi-ethnic populations. The use of metabolomics in medical science research is innovative and promises to provide solutions for disorders with multiple complex underlying determinants such as spontaneous preterm birth.