Glycerophospholipid and detoxification pathways associated with small for gestation age pathophysiology: discovery metabolomics analysis in the SCOPE cohort.

INTRODUCTION: Small for gestational age (SGA) may be associated with neonatal morbidity and mortality. Our understanding of the molecular pathways implicated is poor. OBJECTIVES: Our aim was to determine the metabolic pathways involved in the pathophysiology of SGA and examine their variation between maternal biofluid samples. METHODS: Plasma (Cork) and urine (Cork, Auckland) samples were collected at 20 weeks' gestation from nulliparous low-risk pregnant women participating in the SCOPE study. Women who delivered an SGA infant (birthweight < 10th percentile) were matched to controls (uncomplicated pregnancies). Metabolomics (urine) and lipidomics (plasma) analyses were performed using ultra performance liquid chromatography-mass spectrometry. Features were ranked based on FDR adjusted p-values from empirical Bayes analysis, and significant features putatively identified. RESULTS: Lipidomics plasma analysis revealed that 22 out of the 33 significantly altered lipids annotated were glycerophospholipids; all were detected in higher levels in SGA. Metabolomic analysis identified reduced expression of metabolites associated with detoxification (D-Glucuronic acid, Estriol-16-glucuronide), nutrient absorption and transport (Sulfolithocholic acid) pathways. CONCLUSIONS: This study suggests higher levels of glycerophospholipids, and lower levels of specific urine metabolites are implicated in the pathophysiology of SGA. Further research is needed to confirm these findings in independent samples.

Adverse perinatal outcomes are associated with severe maternal morbidity and mortality: evidence from a national multicentre cross-sectional study.

PURPOSE: To assess the association between maternal potentially life-threatening conditions (PLTC), maternal near miss (MNM), and maternal death (MD) with perinatal outcomes. METHODS: Cross-sectional study in 27 Brazilian referral centers from July, 2009 to June, 2010. All women presenting any criteria for PLTC and MNM, or MD, were included. Sociodemographic and obstetric characteristics were evaluated in each group of maternal outcomes. Childbirth and maternal morbidity data were related to perinatal adverse outcomes (5th min Apgar score < 7, fetal death, neonatal death, or any of these). The Chi-squared test evaluated the differences between groups. Multiple regression analysis adjusted for the clustering design effect identified the independently associated maternal factors with the adverse perinatal outcomes (prevalence ratios; 95% confidence interval). RESULTS: Among 8271 cases of severe maternal morbidity, there were 714 cases of adverse perinatal outcomes. Advanced maternal age, low level of schooling, multiparity, lack of prenatal care, delays in care, preterm birth, and adverse perinatal outcomes were more common among MNM and MD. Both MNM and MD were associated with Apgar score (2.39; 1.68-3.39); maternal hemorrhage was the most prevalent characteristic associated with fetal death (2.9, 95% CI 1.81-4.66) and any adverse perinatal outcome (2.16; 1.59-2.94); while clinical/surgical conditions were more related to neonatal death (1.56; 1.08-2.25). CONCLUSION: We confirmed the association between MNM and MD with adverse perinatal outcomes. Maternal and perinatal issues should not be dissociated. Policies aiming maternal care should include social and economic development, and improvements in accessibility to specialized care. These, in turn, will definitively impact on childhood mortality rates.

Fetal Growth Restriction Prediction: How to Move beyond.

The actual burden and future burden of the small-for-gestational-age (SGA) babies turn their screening in pregnancy a question of major concern for clinicians and policymakers. Half of stillbirths are due to growth restriction in utero, and possibly, a quarter of livebirths of low- and middle-income countries are SGA. Growing body of evidence shows their higher risk of adverse outcomes at any period of life, including increased rates of neurologic delay, noncommunicable chronic diseases (central obesity and metabolic syndrome), and mortality. Although there is no consensus regarding its definition, birthweight centile threshold, or follow-up, we believe birthweight <10th centile is the most suitable cutoff for clinical and epidemiological purposes. Maternal clinical factors have modest predictive accuracy; being born SGA appears to be of transgenerational heredity. Addition of ultrasound parameters improves prediction models, especially using estimated fetal weight and abdominal circumference in the 3rd trimester of pregnancy. Placental growth factor levels are decreased in SGA pregnancies, and it is the most promising biomarker in differentiating angiogenesis-related SGA from other causes. Unfortunately, however, only few societies recommend universal screening. SGA evaluation is the first step of a multidimensional approach, which includes adequate management and long-term follow-up of these newborns. Apart from only meliorating perinatal outcomes, we hypothesize SGA screening is a key for socioeconomic progress.

Approaching literature review for academic purposes: The Literature Review Checklist.

A sophisticated literature review (LR) can result in a robust dissertation/thesis by scrutinizing the main problem examined by the academic study; anticipating research hypotheses, methods and results; and maintaining the interest of the audience in how the dissertation/thesis will provide solutions for the current gaps in a particular field. Unfortunately, little guidance is available on elaborating LRs, and writing an LR chapter is not a linear process. An LR translates students' abilities in information literacy, the language domain, and critical writing. Students in postgraduate programs should be systematically trained in these skills. Therefore, this paper discusses the purposes of LRs in dissertations and theses. Second, the paper considers five steps for developing a review: defining the main topic, searching the literature, analyzing the results, writing the review and reflecting on the writing. Ultimately, this study proposes a twelve-item LR checklist. By clearly stating the desired achievements, this checklist allows Masters and Ph.D. students to continuously assess their own progress in elaborating an LR. Institutions aiming to strengthen students' necessary skills in critical academic writing should also use this tool.

Asthma in pregnancy: association between the Asthma Control Test and the Global Initiative for Asthma classification and comparisons with spirometry.

OBJECTIVE: The aim of this study was to identify a possible association between the assessment of clinical asthma control using the Asthma Control Test (ACT) and the Global Initiative for Asthma (GINA) classification and to perform comparisons with values of spirometry. STUDY DESIGN: Through this cross-sectional study, 103 pregnant women with asthma were assessed in the period from October 2010 to October 2013 in the asthma pregnancy clinic at the Clinical Hospital of the Federal University of Pernambuco. Questionnaires concerning the level of asthma control were administered using the Global Initiative for Asthma classification, the Asthma Control Test validated for asthmatic expectant mothers and spirometry; all three methods of assessing asthma control were performed during the same visit between the twenty-first and twenty-seventh weeks of pregnancy. RESULTS: There was a significant association between clinical asthma control assessment using the Asthma Control Test and the Global Initiative for Asthma classification (p<0.001). There were also significant associations between the results of the subjective instruments of asthma (the GINA classification and the ACT) and evidence of lung function by spirometry. CONCLUSIONS: This study shows that both the Global Initiative for Asthma classification and the Asthma Control Test can be used for asthmatic expectant mothers to assess the clinical control of asthma, especially at the end of the second trimester, which is assumed to be the period of worsening asthma exacerbations during pregnancy. We highlight the importance of the Asthma Control Test as a subjective instrument with easy application, easy interpretation and good reproducibility that does not require spirometry to assess the level of asthma control and can be used in the primary care of asthmatic expectant mothers.

The prevalence of perinatal depression and its associated factors in two different settings in Brazil.

BACKGROUND: The prevalence of antepartum and postpartum depression (PPD) and its association with certain risk factors was evaluated. METHOD: The Edinburgh Postnatal Depression Scale (EPDS) was applied and sociodemographic data was obtained at the beginning of the third trimester of pregnancy and at 4-6 weeks postpartum. RESULTS: The prevalence of depression was 24.3% during pregnancy (n=600 women) and 10.8% in the postpartum period (n=555). The factors independently associated with antepartum depression were the absence of a partner (PRadj 1.93; 95%CI: 1.44-2.58), a lower socioeconomic class (1.75; 1.18-2.60), being non-white (1.48; 1.09-2.01) and multiparity (1.32; 1.01-1.74). For postpartum depression, the factors were the occurrence of psychological violence (PRadj 3.31; 95%CI: 2.02-5.43), use of alcohol during pregnancy (2.14; 1.33-3.45), being non-white (1.85; 1.11-3.08) and physical violence (2.14; 1.13-4.08). The sensitivity of depression during pregnancy as a predictor of PPD was 75%, while specificity was 81%. There were no differences between the two settings. LIMITATIONS: EDPS does not diagnose depression and as a screening instrument it could overestimate the true prevalence of depression. CONCLUSIONS: The use of the EPDS instrument during pregnancy would allow a screening for identifying women at higher risk of developing PPD and then a proposal of specific interventions to manage this condition. Postpartum depression was prevalent in around 10% of the women and was associated with unfavorable sociodemographic conditions including the use of alcohol and with the occurrence of psychological and physical violence.

Effect of a physical exercise program during pregnancy on uteroplacental and fetal blood flow and fetal growth: a randomized controlled trial.

OBJECTIVE: To estimate the effect of supervised physical exercise on maternal physical fitness, fetoplacental blood flow, and fetal growth. METHODS: This was a randomized controlled trial comparing three groups of pregnant women. Groups were as follows: exercise initiated at 13 weeks (group A); exercise initiated at 20 weeks (group B); and a control group (no supervised exercise; group C). The women in groups A and B walked at moderate intensity three times weekly. Physical fitness level was evaluated at weeks 13, 20, and 28. Fetal growth and uteroplacental blood flow were evaluated monthly. Birth weight was registered. Analysis of variance for repeat measures was used for outcomes evaluated throughout pregnancy. Risk ratio was used as a measure of the relative risk of preeclampsia, fetal growth restriction, macrosomia, small-for-gestational-age newborns, and large-for-gestational-age newborns. RESULTS: All the women analyzed completed more than 85% of the program. According to the evaluation conducted at week 28, physical fitness improved, with mean maximal oxygen consumptions (VO2max) of 27.3±4.3 (group A), 28±3.3 (group B), and 25.5±3.8 (group C; P=.03). Mean birth weights were 3,279±453 g (group A), 3,285±477 g (group B), and 3,378±593 g (group C; P=.53), with no difference in the frequency of large for gestational age or small for gestational age. No association was found between the practice of physical activity and the variables investigated (preeclampsia, fetal weight, blood pressure, and pulsatility index of the uterine, umbilical, and middle cerebral arteries). CONCLUSION: Moderate-intensity walking improved the physical fitness level of healthy, pregnant, previously sedentary women without affecting fetoplacental blood flow or fetal growth. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00641550. LEVEL OF EVIDENCE: II.