Metabolomics applied to maternal and perinatal health : a review of new frontiers with a translation potential

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and “omics” sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent “boom” in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies

Profile of calories and nutrients intake in a Brazilian multicenter study of nulliparous women

Objective: To assess the calorie intake and nutritional content of the maternal diet in regions with different culinary traditions and typical foods, and to understand the nutritional profile so as to provide information about the consumption of this population and promote maternal and perinatal health. Methods: From a cohort of 1145 pregnant women with diverse socio-backgrounds we analyzed the dietary characteristics profile according to three guidelines and compared the differences between regions of Brazil. Results: Women from the northeast had the lowest level of income, occupation, education, and age (P < 0.001). Intakes of unprocessed/minimally processed foods and processed foods were more prevalent in women from the northeast than in southern/southeastern women (P < 0.001). The consumption of dairy products and vegetables was less than the recommended intake, with lower intake in southern/southeastern women (P < 0.001). This study showed a lower consumption of dairy and vegetables, with a shortfall of vitamins K and D, iron, calcium, folate, magnesium, and chromium from natural and fortified foods. We observed a greater consumption of unprocessed or minimally processed food in women from the northeast of Brazil. Conclusion: Our findings indicate the importance of differentiating the source of calorie intake between regional nutritional guidance and the diversity of local cuisine

The food patterns of a multicenter cohort of Brazilian nulliparous pregnant women

Assessment of human nutrition is a complex process, in pregnant women identify dietary patterns through mean nutrient consumption can be an opportunity to better educate women on how to improve their overall health through better eating. This exploratory study aimed to identify a posteriori dietary patterns in a cohort of nulliparous pregnant women. The principal component analysis (PCA) technique was performed, with Varimax orthogonal rotation of data extracted from the 24-h dietary recall, applied at 20 weeks of gestation. We analysed 1.145 dietary recalls, identifying five main components that explained 81% of the dietary pattern of the sample. Dietary patterns found were: Obesogenic, represented by ultra-processed foods, processed foods, and food groups rich in carbohydrates, fats and sugars; Traditional, most influenced by natural, minimally processed foods, groups of animal proteins and beans; Intermediate was similar to the obesogenic, although there were lower loads; Vegetarian, which was the only good representation of fruits, vegetables and dairy products; and Protein, which best represented the groups of proteins (animal and vegetable). The obesogenic and intermediate patterns represented over 37% of the variation in food consumption highlighting the opportunity to improve maternal health especially for women at first mothering

Proposal of MUAC as a fast tool to monitor pregnancy nutritional status : results from a cohort study in Brazil

Objective: In Brazil, although the assessment of maternal nutritional status is recommended using body mass index (BMI), this is only possible in settings adequately prepared. Midupper arm circumference (MUAC) is another biological variable identified as a tool for rapid assessment of nutritional status that is correlated with BMI. Therefore, we aim to surrogate BMI by MUAC cut-offs for rapid screening of maternal nutritional status starting at midpregnancy. Design: Analysis of the multicentre cohort study entitled ‘Preterm SAMBA’ using an approach of validation of diagnostic test. Setting: Outpatient prenatal care clinics from five tertiary maternity hospitals from three different Brazilian regions. Participants: 1165 pregnant women attending prenatal care services from 2015 to 2018 and with diverse ethnic characteristics who were enrolled at midpregnancy and followed in three visits at different gestational weeks. Primary and secondary outcome measures: Sensitivity, specificity, positive and negative predictive values, likelihood ratio and accuracy of MUAC being used instead of BMI for the assessment of nutritional status of women during pregnancy. Results: We found a strong correlation between MUAC and BMI, in the three set points analysed (r=0.872, 0.870 and 0.831, respectively). Based on BMI categories of nutritional status, we estimated the best MUAC cut-off points, finding measures according to each category: underweight 30.15 cm (19–21 weeks), >30.60 cm (27–29 weeks) and >30.25 cm (37–39 weeks) per gestational week. Therefore, we defined as adequate between 25.75–28.10 cm (19–21 weeks), 25.75–28.70 cm (27–29 weeks) and 25.75–29.45 cm (37–39 weeks) of MUAC. Conclusion: We conclude that MUAC can be useful as a surrogate for BMI as a faster screening of nutritional status in pregnant women

Head circumference as an epigenetic risk factor for maternal nutrition

Nutrition indicators for malnutrition can be screened by many signs such as stunting, underweight or obesity, muscle wasting, and low caloric and nutrients intake. Those deficiencies are also associated with low socioeconomic status. Anthropometry can assess nutritional status by maternal weight measurements during pregnancy. However, most studies have focused primarily on identifying changes in weight or Body Mass Index (BMI), and their effects on neonatal measures at present time. Whereas head circumference (HC) has been associated with nutrition in the past. When the mother was exposed to poor nutrition and unfavorable social conditions during fetal life, it was hypothesized that the intergenerational cycle was potentially mediated by epigenetic mechanisms. To investigate this theory, maternal head circumference (MHC) was associated with neonatal head circumference (NHC) in pregnant women without preexisting chronic conditions, differentiated by sociodemographic characteristics. A multiple linear regression model showed that each 1 cm-increase in MHC correlated with a 0.11 cm increase in NHC (β95% CI 0.07 to 0.15). Notwithstanding, associations between maternal and neonatal anthropometrics according to gestational age at birth have been extensively explained. Path analysis showed the influence of social status and the latent variable was socioeconomic status. A model of maternal height and head circumference was tested with effects on neonatal HC. The social variable lacked significance to predict neonatal HC in the total sample (p = 0.212) and in the South/Southeast (p = 0.095), in contrast to the Northeast (p = 0.047). This study highlights the potential intergenerational influence of maternal nutrition on HC, suggesting that maternal nutrition may be more relevant in families with major social vulnerability

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

Polycystic Ovary Syndrome And Chronic Autoimmune Thyroiditis.

Polycystic ovary syndrome (PCOS) has been associated with an autoimmune origin, either per se or favoring the onset of autoimmune diseases, from a stimulatory action on the inflammatory response. Thus, autoimmune thyroiditis (AIT) could be more prevalent among women with PCOS. To evaluate the prevalence of AIT in women with PCOS. It was a cross-sectional study, in a tertiary center, including 65 women with PCOS and 65 women without this condition. Clinical and laboratory parameters were evaluated and a thyroid ultrasound scan was performed. Levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase (anti-TPO) antibodies, anti-thyroglobulin (anti-TG) antibodies, and thyroid ultrasound findings were evaluated. The prevalence of subclinical hypothyroidism (SCH) in women with PCOS was 16.9% and 6.2% in the non-PCOS group. AIT was more common in the PCOS group compared with the non-PCOS group (43.1% versus 26.2%). But, when it was adjusted by weight and insulin resistance, the difference in the thyroiditis risk was not observed (OR 0.78, CI 0.28-2.16). AIT risk was similar in the PCOS and the non-PCOS group. SCH are more common in women with PCOS, highlighting a need for periodic monitoring of thyroid function.3148-5

Metabolomics applied to maternal and perinatal health : a review of new frontiers with a translation potential

The prediction or early diagnosis of maternal complications is challenging mostly because the main conditions, such as preeclampsia, preterm birth, fetal growth restriction, and gestational diabetes mellitus, are complex syndromes with multiple underlying mechanisms related to their occurrence. Limited advances in maternal and perinatal health in recent decades with respect to preventing these disorders have led to new approaches, and “omics” sciences have emerged as a potential field to be explored. Metabolomics is the study of a set of metabolites in a given sample and can represent the metabolic functioning of a cell, tissue or organism. Metabolomics has some advantages over genomics, transcriptomics, and proteomics, as metabolites are the final result of the interactions of genes, RNAs and proteins. Considering the recent “boom” in metabolomic studies and their importance in the research agenda, we here review the topic, explaining the rationale and theory of the metabolomic approach in different areas of maternal and perinatal health research for clinical practitioners. We also demonstrate the main exploratory studies of these maternal complications, commenting on their promising findings. The potential translational application of metabolomic studies, especially for the identification of predictive biomarkers, is supported by the current findings, although they require external validation in larger datasets and with alternative methodologies

Maternal Nutrition Status Associated with Pregnancy-Related Adverse Outcomes

Although maternal nutrition has an impact on fetal development and gestational outcome, tracking maternal nutrition in outpatient practice is still complex and involves proper technical capacitation in this area. Nevertheless, the association between nutritional variables may broaden the ability to predict the occurrence of gestational disorders and prevention management. We aimed to identify factors that could indicate the probability of adverse outcomes in mid-pregnancy. From a cohort of 1165 nulliparous pregnant women without any previous disease, the nutritional status was assessed by body mass index (BMI) and mid-upper arm circumference (MUAC), associated with dietary patterns and sociodemographic characteristics. Two predictive models with nutritional status for screening the occurrence of adverse outcomes of preterm birth, gestational diabetes mellitus, small-for-gestational-age newborns and preeclampsia were developed. The odds of adverse outcomes were higher in non-white (p &lt; 0.05) obese women and with high protein consumption. There was no significant difference between the models, with an overall accuracy of 63% for both models and a probability of success in predicting adverse outcomes (BMI = 61%, MUAC = 52%). This study of Brazilian pregnant nulliparous women offers two possible options for early tracking of adverse gestational outcomes that should be further externally validated

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