Pulmonary vascular reactivity in growth restricted fetuses using computational modelling and machine learning analysis of fetal Doppler waveforms.

The aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24-37 weeks of gestation and data were acquired before and after oxygen administration. After, Machine Learning (ML) and a computational model were used on the Doppler waveforms to classify individuals and estimate pulmonary vascular resistance (PVR). Our results showed lower mean velocity time integral (VTI) in the main pulmonary and intrapulmonary arteries in baseline conditions in FGR individuals. Delta changes of the main pulmonary artery VTI and intrapulmonary artery pulsatility index before and after hyperoxygenation were significantly greater in FGR when compared with controls. Also, ML identified two clusters: A (including 66% controls and 34% FGR) with similar Doppler traces over time and B (including 33% controls and 67% FGR) with changes after hyperoxygenation. The computational model estimated the ratio of PVR before and after maternal hyperoxygenation which was closer to 1 in cluster A (cluster A 0.98 ± 0.33 vs cluster B 0.78 ± 0.28, p = 0.0156). Doppler ultrasound allows the detection of significant changes in pulmonary vasculature in most FGR at baseline, and distinct responses to hyperoxygenation. Future studies are warranted to assess its potential applicability in the clinical management of FGR.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

10. Role of high dimensional technology in preeclampsia (omics in preeclampsia).

Preeclampsia is a pregnancy-specific disease that has no known precise cause. Integrative biology approach based on multi-omics has been applied to identify upstream pathways and better understand the pathophysiology of preeclampsia. At DNA level, genomics and epigenomics studies have revealed numerous genetic variants associated with preeclampsia, including those involved in regulating blood pressure and immune response. Transcriptomics analyses have revealed altered expression of genes in preeclampsia, particularly those related to inflammation and angiogenesis. At protein level, proteomics studies have identified potential biomarkers for preeclampsia diagnosis and prediction in addition to revealing the main pathophysiological pathways involved in this disease. At metabolite level, metabolomics has highlighted altered lipid and amino acid metabolisms in preeclampsia. Finally, microbiomics studies have identified dysbiosis in the gut and vaginal microbiota in pregnant women with preeclampsia. Overall, omics technologies have improved our understanding of the complex molecular mechanisms underlying preeclampsia. However, further research is warranted to fully integrate and translate these omics findings into clinical practice.

Maternal Stress, Anxiety, Well-Being, and Sleep Quality in Pregnant Women throughout Gestation.

BACKGROUND: Maternal stress, anxiety, well-being, and sleep quality during pregnancy have been described as influencing factors during pregnancy. AIM: We aimed to describe maternal stress, anxiety, well-being, and sleep quality in pregnant women throughout gestation and their related factors. METHODS: A prospective study including pregnant women attending BCNatal, in Barcelona, Spain (n = 630). Maternal stress and anxiety were assessed by the Perceived Stress Scale (PSS) and State-Trait Anxiety Inventory (STAI)-validated questionnaires. Maternal well-being was assessed using the World Health Organization Well-Being Index Questionnaire (WHO-5), and sleep quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). All questionnaires were obtained twice during the second and third trimester of pregnancy. A multivariate analysis was conducted to assess factors related to higher maternal stress and anxiety and worse well-being and sleep quality. RESULTS: High levels of maternal stress were reported in 23.1% of participants at the end of pregnancy, with maternal age <40 years (OR 2.02; 95% CI 1.08-3.81, p = 0.03), non-white ethnicity (OR 2.09; 95% CI 1.19-4.02, p = 0.01), and non-university studies (OR 1.86; 95% CI 1.08-3.19, p = 0.02) being the parameters mostly associated with it. A total of 20.7% of women had high levels of anxiety in the third trimester and the presence of psychiatric disorders (OR 3.62; 95% CI 1.34-9.78, p = 0.01) and non-university studies (OR 1.70; 95% CI 1.11-2.59, p = 0.01) provided a significant contribution to high anxiety at multivariate analysis. Poor maternal well-being was observed in 26.5% of women and a significant contribution was provided by the presence of psychiatric disorders (OR 2.96; 95% CI 1.07-8.25, p = 0.04) and non-university studies (OR 1.74; 95% CI 1.10-2.74, p = 0.02). Finally, less sleep quality was observed at the end of pregnancy (p < 0.001), with 81.1% of women reporting poor sleep quality. CONCLUSION: Maternal stress and anxiety, compromised maternal well-being, and sleep quality disturbances are prevalent throughout pregnancy. Anxiety and compromised sleep quality may increase over gestation. The screening of these conditions at different stages of pregnancy and awareness of the associated risk factors can help to identify women at potential risk.

Cardiometabolic sex differences in adults born small for gestational age.

Aim: This study aimed to assess the cardiometabolic sex similarities and differences in adults born small for gestational age. Methods: This study was an ambispective cohort study from a birth registry in Barcelona, Spain, including 523 adult participants (20-40 years-old) subdivided as born small for gestational age (SGA, if birth weight <10th centile) or adequate fetal growth for gestational age (AGA). Cardiometabolic health was assessed by echocardiography, electrocardiogram, blood pressure measurement, vascular ultrasound, anthropometric measurements, and serum glycemia and lipid profile. Stratified analyses by sex were performed by estimation of adjusted absolute difference (AAD) using inverse probability weighting. Results: Compared with AGA, the stratified analyses by sex showed a more pronounced reduction in ejection fraction [AAD: female -1.73 (95% CI -3.2 to -0.28) vs. male -1.33 (-3.19 to 0.52)] and increment in heart rate [female 3.04 (0.29-5.8) vs. male 2.25 (-0.82 to 5.31)] in SGA females compared with SGA males. In contrast, a more pronounced reduction in PR interval [female -1.36 (-6.15 to 3.42) vs. male -6.61 (-11.67 to -1.54)] and an increase in systolic blood pressure [female 0.06 (-2.7 to 2.81) vs. male 2.71 (-0.48 to 5.9)] and central-to-peripheral fat ratio [female 0.05 (-0.03 to 0.12) vs. male 0.40 (0.17-0.62)] were mainly observed in SGA male compared with SGA female. Conclusions: Sex differences were observed in the effect of SGA on cardiometabolic endpoints with female being more prone to cardiac dysfunction and male to electrocardiographic, vascular, and metabolic changes. Future research including sex-stratification data is warranted.

Effects of Mediterranean diet or mindfulness-based stress reduction on fetal and neonatal brain development: a secondary analysis of a randomized clinical trial.

BACKGROUND: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment. OBJECTIVE: This study aimed to investigate if structured lifestyle interventions involving a Mediterranean diet or mindfulness-based stress reduction during pregnancy are associated with differences in fetal and neonatal brain development. STUDY DESIGN: This was a secondary analysis of the randomized clinical trial Improving Mothers for a Better Prenatal Care Trial Barcelona that was conducted in Barcelona, Spain, from 2017 to 2020. Participants with singleton pregnancies were randomly allocated into 3 groups, namely Mediterranean diet intervention, stress reduction program, or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week mindfulness-based stress reduction program adapted for pregnancy. Magnetic resonance imaging of 90 fetal brains was performed at 36 to 39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale was completed for 692 newborns at 1 to 3 months. Fetal outcomes were the total brain volume and lobular or regional volumes obtained from a 3-dimensional reconstruction and semiautomatic segmentation of magnetic resonance images. Neonatal outcomes were the 6 clusters scores of the Neonatal Neurobehavioral Assessment Scale. Multiple regression analyses were conducted to assess the association between the interventions and the fetal and neonatal outcomes. RESULTS: When compared with the usual care group, the offspring exposed to a maternal Mediterranean diet had a larger total fetal brain volume (mean, 284.11 cm3; standard deviation, 23.92 cm3 vs 294.01 cm3; standard deviation, 26.29 cm3; P=.04), corpus callosum (mean, 1.16 cm3; standard deviation, 0.19 cm3 vs 1.26 cm3; standard deviation, 0.22 cm3; P=.03), and right frontal lobe (44.20; standard deviation, 4.09 cm3 vs 46.60; standard deviation, 4.69 cm3; P=.02) volumes based on magnetic resonance imaging measures and higher scores in the Neonatal Neurobehavioral Assessment Scale clusters of autonomic stability (mean, 7.4; standard deviation, 0.9 vs 7.6; standard deviation, 0.7; P=.04), social interaction (mean, 7.5; standard deviation, 1.5 vs 7.8; standard deviation, 1.3; P=.03), and range of state (mean, 4.3; standard deviation, 1.3 vs 4.5; standard deviation, 1.0; P=.04). When compared with the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume (1.63; standard deviation, 0.32 m3 vs 1.79; standard deviation, 0.30 cm3; P=.03) based on magnetic resonance imaging and higher scores in the Neonatal Neurobehavioral Assessment Scale for regulation of state (mean, 6.0; standard deviation, 1.8 vs 6.5; standard deviation, 1.5; P<.01). CONCLUSION: Maternal structured lifestyle interventions involving the promotion of a Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development.

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.

Diet quality and nutrient density in pregnant women according to adherence to Mediterranean diet.

Background and aims: The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients. Methods: This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders. Results: A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, n = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, p < 0.001), magnesium (0% vs. 7.6%, p = 0.001), iron (24.5% vs. 74.1%, p < 0.001), and vitamin B9 (0% vs. 29.8%, p < 0.001), vitamin C (0% vs. 1.9%, p = 0.033), and vitamin D (61.5% vs. 92.8%, p < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet. Conclusion: High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies.

Effect of a Mediterranean Diet or Mindfulness-Based Stress Reduction During Pregnancy on Child Neurodevelopment: A Prespecified Analysis of the IMPACT BCN Randomized Clinical Trial.

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment. Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years. Design, Setting, and Participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks' gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022. Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols. Main Outcomes and Measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age. Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (ß, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (ß, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (ß, 4.75; 95% CI, 0.54-8.85; P = .02). Conclusions and Relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT03166332.

Effects of a Mediterranean Diet Intervention on Maternal Stress, Well-Being, and Sleep Quality throughout Gestation-The IMPACT-BCN Trial.

Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation.

Preterm Prelabour Rupture of Membranes before Viability in Twin Pregnancies: What Can We Expect?

Preterm prelabour rupture of membranes (PPROMs) before viability carries significant perinatal mortality and morbidity. Clinical management and prenatal counselling are a challenge, especially in twin pregnancies, due to scarce evidence on how previable PPROM affects this population. The aim of this study was to describe pregnancy outcomes of twin pregnancies complicated with previable PPROM and evaluate potential prognostic factors that may predict perinatal mortality. A retrospective cohort including dichorionic and monochorionic diamniotic twin pregnancies complicated with PPROM before 24 + 0 weeks of pregnancy was evaluated. Perinatal outcomes of pregnancies managed expectantly were described. Factors predicting perinatal mortality or reaching periviability (defined from 23 + 0 weeks onwards) were evaluated. Of the 45 patients included, 7 (15.6%) spontaneously delivered within the first 24 h after diagnosis. Two patients (5.3%) requested selective termination of the affected twin. In the 36 ongoing pregnancies that opted for expectant management, the overall survival rate was 35/72 (48.6%). There were 25/36 (69.4%) patients who delivered after 23 + 0 weeks of pregnancy. When periviability was achieved, neonatal survival increased up to 35/44 (79.5%). Gestational age at delivery was the only independent risk factor of perinatal mortality. The overall survival rate of twin pregnancies complicated with previable PPROM is poor but similar to singletons. No prognostic factors, apart from achieving periviability, were identified as individual predictors of perinatal mortality.

Cardiac remodeling from the fetus to adulthood.

Prenatal cardiac remodeling refers to in utero changes in the fetal heart that occur as a response to an adverse intrauterine environment. In this article, we will review the main mechanisms leading to cardiac remodeling and dysfunction, summarizing and describing the major pathological conditions that have been reported to be related to this in utero plastic adaptive process. We will also recap the current evidence regarding the persistence of fetal cardiac remodeling and dysfunction, both in infancy and later in adult life. Moreover, we will discuss primary, secondary, and tertiary preventive measures and future clinical and research aspects.

An automatic pipeline for atlas-based fetal and neonatal brain segmentation and analysis.

BACKGROUND AND OBJECTIVE: The automatic segmentation of perinatal brain structures in magnetic resonance imaging (MRI) is of utmost importance for the study of brain growth and related complications. While different methods exist for adult and pediatric MRI data, there is a lack for automatic tools for the analysis of perinatal imaging. METHODS: In this work, a new pipeline for fetal and neonatal segmentation has been developed. We also report the creation of two new fetal atlases, and their use within the pipeline for atlas-based segmentation, based on novel registration methods. The pipeline is also able to extract cortical and pial surfaces and compute features, such as curvature, local gyrification index, sulcal depth, and thickness. RESULTS: Results show that the introduction of the new templates together with our segmentation strategy leads to accurate results when compared to expert annotations, as well as better performances when compared to a reference pipeline (developing Human Connectome Project (dHCP)), for both early and late-onset fetal brains. CONCLUSIONS: These findings show the potential of the presented atlases and the whole pipeline for application in both fetal, neonatal, and longitudinal studies, which could lead to dramatic improvements in the understanding of perinatal brain development.

Association of central obesity with unique cardiac remodelling in young adults born small for gestational age.

AIMS: Being born small for gestational age (SGA, 10% of all births) is associated with increased risk of cardiovascular mortality in adulthood together with lower exercise tolerance, but mechanistic pathways are unclear. Central obesity is known to worsen cardiovascular outcomes, but it is uncertain how it affects the heart in adults born SGA. We aimed to assess whether central obesity makes young adults born SGA more susceptible to cardiac remodelling and dysfunction. METHODS AND RESULTS: A perinatal cohort from a tertiary university hospital in Spain of young adults (30-40 years) randomly selected, 80 born SGA (birth weight below 10th centile) and 75 with normal birth weight (controls) was recruited. We studied the associations between SGA and central obesity (measured via the hip-to-waist ratio and used as a continuous variable) and cardiac regional structure and function, assessed by cardiac magnetic resonance using statistical shape analysis. Both SGA and waist-to-hip were highly associated to cardiac shape (F = 3.94, P < 0.001; F = 5.18, P < 0.001 respectively) with a statistically significant interaction (F = 2.29, P = 0.02). While controls tend to increase left ventricular end-diastolic volumes, mass and stroke volume with increasing waist-to-hip ratio, young adults born SGA showed a unique response with inability to increase cardiac dimensions or mass resulting in reduced stroke volume and exercise capacity. CONCLUSION: SGA young adults show a unique cardiac adaptation to central obesity. These results support considering SGA as a risk factor that may benefit from preventive strategies to reduce cardiometabolic risk.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Nasopharyngeal microbiota profiling of pregnant women with SARS-CoV-2 infection.

We aimed to analyze the nasopharyngeal microbiota profiles in pregnant women with and without SARS-CoV-2 infection, considered a vulnerable population during COVID-19 pandemic. Pregnant women were enrolled from a multicenter prospective population-based cohort during the first SARS-CoV-2 wave in Spain (March-June 2020 in Barcelona, Spain) in which the status of SARS-CoV-2 infection was determined by nasopharyngeal RT-PCR and antibodies in peripheral blood. Women were randomly selected for this cross-sectional study on microbiota. DNA was extracted from nasopharyngeal swab samples, and the V3-V4 region of the 16S rRNA of bacteria was amplified using region-specific primers. The differential abundance of taxa was tested, and alpha/beta diversity was evaluated. Among 76 women, 38 were classified as positive and 38 as negative for SARS-CoV-2 infection. All positive women were diagnosed by SARS-CoV-2 IgG and IgM/IgA antibodies, and 14 (37%) also had a positive RT-PCR. The overall composition of the nasopharyngeal microbiota differ in pregnant women with SARS-CoV-2 infection (positive SARS-CoV-2 antibodies), compared to those without the infection (negative SARS-CoV-2 antibodies) (p = 0.001), with a higher relative abundance of the Tenericutes and Bacteroidetes phyla and a higher abundance of the Prevotellaceae family. Infected women presented a different pattern of microbiota profiling due to beta diversity and higher richness (observed ASV < 0.001) and evenness (Shannon index < 0.001) at alpha diversity. These changes were also present in women after acute infection, as revealed by negative RT-PCR but positive SARS-CoV-2 antibodies, suggesting a potential association between SARS-CoV-2 infection and long-lasting shift in the nasopharyngeal microbiota. No significant differences were reported in mild vs. severe cases. This is the first study on nasopharyngeal microbiota during pregnancy. Pregnant women with SARS-CoV-2 infection had a different nasopharyngeal microbiota profile compared to negative cases.

Maternal Dietary Inflammatory Index during Pregnancy Is Associated with Perinatal Outcomes: Results from the IMPACT BCN Trial.

The information available on the effects of maternal dietary habits on systemic inflammation and adverse maternal outcomes is limited. We aimed to evaluate whether Dietary Inflammatory Index (DII) score during pregnancy is associated with maternal body mass index (BMI), Mediterranean diet (MD) adherence, and perinatal outcomes. At 19−23 weeks' gestation, 1028 pregnant women were recruited. Dietary information was assessed using a 17-item dietary score to evaluate MD adherence and a validated 151-item food frequency questionnaire. DII score was established according to 33 food and nutritional proinflammatory and anti-inflammatory items. Participants were distributed into tertiles according to the DII score, where a lower DII score (first tertile) represented an anti-inflammatory diet and the third tertile represented the more proinflammatory diet. Maternal characteristics and perinatal outcomes were collected, and newborns' birthweight percentiles were calculated. Adjusted logistic regression models were used to assess the association of the DII score with maternal and perinatal characteristics, setting the third tertile as the reference group. Women in the third tertile showed lower adherence to MD score compared to the first tertile: median (25th to 75th percentile) 9 (7 to 11) vs. 6 (4.25 to 8), p < 0.001. The proinflammatory diet was significantly associated with a higher maternal pre-pregnancy BMI (adjusted ß = 0.88; 95% CI: 0.31 to 1.45) and lower newborn's birthweight percentile (adjusted ß = −9.84th; 95% CI: −19.6 to −0.12). These data show that a proinflammatory diet profile may be associated with maternal overweight and fetal undergrowth.