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BACKGROUND: Maternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as "stress signals" in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues. RESULTS: Our mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs. CONCLUSION: Our results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes.
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Vesículas Extracelulares , Placenta , Estrés Psicológico , Animales , Femenino , Embarazo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/fisiología , Placenta/metabolismo , Masculino , Feto , Ratas , Retardo del Crecimiento Fetal/metabolismo , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Intercambio Materno-Fetal/fisiologíaRESUMEN
INTRODUCTION: Undetected high-risk conditions in pregnancy are a leading cause of perinatal mortality in low-income and middle-income countries. A key contributor to adverse perinatal outcomes in these settings is limited access to high-quality screening and timely referral to care. Recently, a low-cost one-dimensional Doppler ultrasound (1-D DUS) device was developed that front-line workers in rural Guatemala used to collect quality maternal and fetal data. Further, we demonstrated with retrospective preliminary data that 1-D DUS signal could be processed using artificial intelligence and deep-learning algorithms to accurately estimate fetal gestational age, intrauterine growth and maternal blood pressure. This protocol describes a prospective observational pregnancy cohort study designed to prospectively evaluate these preliminary findings. METHODS AND ANALYSIS: This is a prospective observational cohort study conducted in rural Guatemala. In this study, we will follow pregnant women (N =700) recruited prior to 18 6/7 weeks gestation until their delivery and early postpartum period. During pregnancy, trained nurses will collect data on prenatal risk factors and obstetrical care. Every 4 weeks, the research team will collect maternal weight, blood pressure and 1-D DUS recordings of fetal heart tones. Additionally, we will conduct three serial obstetric ultrasounds to evaluate for fetal growth restriction (FGR), and one postpartum visit to record maternal blood pressure and neonatal weight and length. We will compare the test characteristics (receiver operator curves) of 1-D DUS algorithms developed by deep-learning methods to two-dimensional fetal ultrasound survey and published clinical pre-eclampsia risk prediction algorithms for predicting FGR and pre-eclampsia, respectively. ETHICS AND DISSEMINATION: Results of this study will be disseminated at scientific conferences and through peer-reviewed articles. Deidentified data sets will be made available through public repositories. The study has been approved by the institutional ethics committees of Maya Health Alliance and Emory University.
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Inteligencia Artificial , Retardo del Crecimiento Fetal , Preeclampsia , Ultrasonografía Doppler , Humanos , Embarazo , Femenino , Preeclampsia/diagnóstico por imagen , Preeclampsia/diagnóstico , Guatemala , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico , Estudios Prospectivos , Ultrasonografía Doppler/métodos , Población Rural , Ultrasonografía Prenatal/métodos , Adulto , Edad Gestacional , Aprendizaje Profundo , HipertensiónRESUMEN
INTRODUCTION: Iodine is an essential mineral for fetal growth and brain development. The aim of this research was to evaluate goiter, iodine deficiency and intrauterine growth restriction in pregnant women of minority ethnic groups in Colombia. METHODS: A cross-sectional study was performed in six non-metropolitan areas of Colombia. RESULTS: A total of 318 Indigenous and Afro-descendant pregnant women were invited to participate: 248 (83.2%) Indigenous and 50 (16.8%) Afro-descendants were studied. The mean age was 24 years (range 13-44 years). Of the women, 130 (43.5%) were from the department of Cauca, 72 (24.1%) were from Córdoba, 28 (9.4%) were from Guajira, 26 (8.8%) were from Sierra Nevada de Santa Marta, 22 (7.4%) were from Amazonas, 16 (5.4%) were from Meta and 4 (1.3%) were from the department of Cesar. A total of 244 (81.8%) were illiterate and 291 (97.7%) were of very low socioeconomic level. Goiter was observed in 69 (23.3%) pregnant women (38 (41.7%) from the department of Cauca, 10 (35.7%) from Guajira, 5 (31.2%) from Meta, 6 (27.2%) from Amazonas and 10 (13.8%) from Córdoba). Iodine deficiency (<100 µg/L) was observed in 42 (14.9%) pregnant women (16 (11.6%) mild (50-99 µg/L), 19 (13.8%) moderate (20-49 µg/L) and 7 (5.1%) severe (<20 µg/L)). Being literate was a protective factor for iodine deficiency (odds ratio (OR)=0.19, 95% confidence interval (CI) 0.04-0.84, p=0.016). Being illiterate and iodine deficient was only a risk factor for goiter (OR=6.72, 95%CI 3.9-9.5, p=0.038) in the department of Cauca. CONCLUSION: A high prevalence of goiter, iodine deficiency and intrauterine growth restriction was observed in minority ethnic groups of Colombia. The highest prevalence and risk was observed in the department of Cauca.
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Retardo del Crecimiento Fetal , Bocio , Yodo , Adolescente , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Colombia/epidemiología , Estudios Transversales , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/etnología , Bocio/epidemiología , Bocio/etnología , Yodo/deficiencia , Yodo/administración & dosificación , Minorías Étnicas y RacialesRESUMEN
Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.
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Biotina , Restricción Calórica , Suplementos Dietéticos , Retardo del Crecimiento Fetal , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Embarazo , Ratas , Restricción Calórica/métodos , Biotina/administración & dosificación , Biotina/farmacología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Retardo del Crecimiento Fetal/prevención & control , Retardo del Crecimiento Fetal/etiología , Resistencia a la Insulina , Modelos Animales de Enfermedad , Síndrome Metabólico/prevención & control , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Fructosa/efectos adversos , Factores de Riesgo Cardiometabólico , Peso Corporal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacosRESUMEN
BACKGROUND: The mitigation measures implemented to face the healthcare emergency brought by COVID 19 pandemic generated an increase in socioeconomic inequities in the most underprivileged population which is also the most threatened in their human rights. In Uruguay, this population is assisted in the public health care system. To analyze how these measures impacted on these mothers and their neonates we selected outcomes that most contributed to neonatal mortality. OBJECTIVE: To analyze the incidence of Preterm Birth (PB), Intrauterine Growth Restriction (IUGR) and Low Birth Weight (LBW) in the public health care system in Uruguay, during the period of time in which the strictest measures were adopted to mitigate the COVID 19 pandemic in 2020 (para-pandemic period) compared to the same period in 2019 (pre-pandemic). METHODS: A retrospective, cross sectional, descriptive study was performed to compare PB, IUGR and LBW from 15 March to 30 September 2019 (before COVID 19 pandemic) to the same period of 2020 (when COVID 19 pandemic bloomed), in the public health care subsystem. The analysis was performed with data from the national perinatal database system (SIP). RESULTS: In 2020, a significative increase in PB, RR: 1.14 (CI 95%: 1.03-1.25), and in LBW, RR: 1.16 (CI 95% 1.02-1.33), was registered compared to 2019 (pre-pandemic period). IUGR also showed an increase, but without statistical significance (4.6% in 2019 vs 5.2% in 2020, RR 1.13 CI 95% 0.98-1.31). The compared groups showed no differences in the distribution of biological confounding variables that could explain the increase in incidence of the main outcomes. CONCLUSIONS: In the absence of other factors that could explain the results we consider that social crisis associated to the restrictive measures implemented in the country to dwindle the effect of the pandemic exacerbated the adverse conditions that affect the reproductive process for those underprivileged women assisted in the public sector, increasing PB and LBW. It is important to consider the future impact of these results on neonatal and infant mortality and to implement social measures to reduce the damage as soon as possible.
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COVID-19 , Recién Nacido de Bajo Peso , Nacimiento Prematuro , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Femenino , Recién Nacido , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Embarazo , Estudios Transversales , Uruguay/epidemiología , Adulto , Factores Socioeconómicos , Retardo del Crecimiento Fetal/epidemiología , SARS-CoV-2 , IncidenciaRESUMEN
OBJECTIVE: The objective of this study was to determine serum fibroblast growth factor-23 levels in preeclampsia, eclampsia, gestational hypertension, and the presence of fetal growth restriction subgroups. METHODS: A total of 55 pregnant women with planned cesarean section were included in this cross-sectional study. They were divided into two groups, namely, control (25) and gestational hypertensive disease (30). The gestational hypertensive disease group was evaluated by dividing it into three subgroups (preeclampsia, eclampsia, and gestational hypertension) according to the clinical and laboratory findings of the disease and two subgroups (presence of fetal growth restriction and absence of fetal growth restriction) according to the birth weight percentile. Demographic parameters, obstetric history, physical examination findings, and laboratory values were evaluated. RESULTS: Demographic parameters and obstetric history were similar between the two groups, while gestational week of delivery was lower in the gestational hypertensive disease group (p=0.002). Laboratory parameters and serum fibroblast growth factor-23 (pg/mL) values were similar between the two groups. In the subgroup analysis for gestational hypertension, preeclampsia, and eclampsia, there was no statistically significant difference in serum fibroblast growth factor-23 levels between gestational hypertension, preeclampsia, eclampsia, and control groups. In the subgroup analysis based on the presence of fetal growth restriction, serum fibroblast growth factor-23 levels were similar to the control group in the gestational hypertensive disease absence of fetal growth restriction, while serum fibroblast growth factor-23 levels and serum calcium levels were statistically significantly lower in the gestational hypertensive disease with the presence of fetal growth restriction (p=0.044 and p<0.001, respectively). CONCLUSION: Serum fibroblast growth factor-23 levels are similar between pregnancies complicated with gestational hypertensive disease and normotensive pregnancies. However, serum fibroblast growth factor-23 levels were found to be lower in pregnancies complicated with gestational hypertensive disease with the presence of fetal growth restriction.
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Biomarcadores , Retardo del Crecimiento Fetal , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Hipertensión Inducida en el Embarazo , Preeclampsia , Humanos , Femenino , Embarazo , Retardo del Crecimiento Fetal/sangre , Estudios Transversales , Adulto , Hipertensión Inducida en el Embarazo/sangre , Factores de Crecimiento de Fibroblastos/sangre , Factor-23 de Crecimiento de Fibroblastos/sangre , Biomarcadores/sangre , Preeclampsia/sangre , Estudios de Casos y Controles , Adulto Joven , Edad Gestacional , Eclampsia/sangreRESUMEN
Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.
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Acetilcisteína , Epigénesis Genética , Retardo del Crecimiento Fetal , Sulfuro de Hidrógeno , Hipoxia , Animales , Sulfuro de Hidrógeno/metabolismo , Acetilcisteína/farmacología , Embrión de Pollo , Humanos , Femenino , Embarazo , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/fisiopatología , Hipoxia/metabolismo , Hipoxia/fisiopatología , Metilación de ADN , Cistationina gamma-Liasa/genética , Cistationina gamma-Liasa/metabolismo , Vasodilatación/efectos de los fármacos , Placenta/metabolismo , Placenta/irrigación sanguínea , Arterias Umbilicales/metabolismoRESUMEN
Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia. Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed. Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant. Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.
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COVID-19 , Preeclampsia , Complicaciones Infecciosas del Embarazo , Resultado del Embarazo , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , Embarazo , Femenino , Preeclampsia/epidemiología , COVID-19/epidemiología , COVID-19/mortalidad , Brasil/epidemiología , Estudios Prospectivos , Adulto , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Factores de Riesgo , Resultado del Embarazo/epidemiología , Prevalencia , Recién Nacido , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/virología , ComorbilidadRESUMEN
We aimed to measure the association between Trypanosoma cruzi infection in pregnancy and reduced fetal growth in the absence of T. cruzi congenital transmission. We conducted a cross-sectional study of secondary data of all singleton live births between 2011 and 2013 in five hospitals from Argentina, Honduras, and Mexico. We excluded newborns with T. cruzi infection. Noninfected pregnant people were those without any positive rapid tests. The main study outcomes were birth weight, head circumference, and length for gestational age and sex. Logistic regression models were adjusted for country, age, education level, and obstetric history. Of the 26,544 deliveries, 459 (1.7%) pregnant people were found by rapid tests to be positive for T. cruzi. Of these, 320 were positive by enzyme-linked immunosorbent assay and 231 had a positive polymerase chain reaction (PCR) test. Uninfected newborns from T. cruzi-infected pregnant people were more likely to have birth weights below the 5th and 10th percentiles and head circumferences below the 3rd and 10th percentiles. Among T. cruzi-infected pregnant people diagnosed by PCR, the odds ratios were 1.58 for birth weight below the 10th percentile (95% CI, 1.12-2.23) and 1.57 for birth weight below the 5th percentile (95% CI, 1.02-2.42). Higher T. cruzi parasitic loads in pregnancy had a stronger association with reduced fetal growth (both in birth weight and head circumference), with an odds ratio of 2.31 (95% CI, 1.36-3.91) for a birth weight below the 5th percentile. The association shows, irrespective of causality, that newborns of pregnancies with T. cruzi have an increased risk of reduced fetal growth. We recommend further studies to assess other potential confounders and the causality of these associations.
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Peso al Nacer , Enfermedad de Chagas , Trypanosoma cruzi , Humanos , Femenino , Embarazo , Enfermedad de Chagas/transmisión , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/congénito , Estudios Transversales , Honduras/epidemiología , Argentina/epidemiología , Trypanosoma cruzi/aislamiento & purificación , Adulto , México/epidemiología , Recién Nacido , Complicaciones Parasitarias del Embarazo/epidemiología , Masculino , Adulto Joven , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/parasitología , Desarrollo FetalRESUMEN
Intrauterine growth restriction (IUGR) affects a large proportion of infants, particularly in underdeveloped countries. Among the main causes of IUGR, maternal endocrine-metabolic dysfunction is highlighted, either due to its high incidence or due to the severity of the immediate and mediated changes that these dysfunctions cause in the fetus and the mother. Although the effects of endocrine and metabolic disorders have been widely researched, there are still no reviews that bring together and summarize the effects of these conditions on bone development in cases of IUGR. Therefore, the present literature review was conducted with the aim of discussing bone changes observed in fetuses with IUGR caused by maternal endocrine-metabolic dysfunction. The main endocrine dysfunctions that occur with IUGR include maternal hyperthyroidism, hypothyroidism, and hypoparathyroidism. Diabetes mellitus, hypertensive disorders, and obesity are the most important maternal metabolic dysfunctions that compromise fetal growth. The bone changes reported in the fetus are, for the most part, due to damage to cell proliferation and differentiation, as well as failures in the synthesis and mineralization of the extracellular matrix, which results in shortening and fragility of the bones. Some maternal dysfunctions, such as hyperthyroidism, have been widely studied, whereas conditions such as hypoparathyroidism and gestational hypertensive disorders require further study regarding the mechanisms underlying the development of bone changes. Similarly, there is a gap in the literature regarding changes related to intramembranous ossification, as most published articles only describe changes in endochondral bone formation associated with IUGR. Furthermore, there is a need for more research aimed at elucidating the late postnatal changes that occur in the skeletons of individuals affected by IUGR and their possible relationships with adult diseases, such as osteoarthritis and osteoporosis.
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Desarrollo Óseo , Retardo del Crecimiento Fetal , Humanos , Retardo del Crecimiento Fetal/fisiopatología , Femenino , Embarazo , Feto , Animales , Enfermedades del Sistema EndocrinoRESUMEN
OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.
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COVID-19 , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , México/epidemiología , COVID-19/epidemiología , SARS-CoV-2 , Retardo del Crecimiento Fetal/epidemiología , Muerte Fetal , Resultado del Embarazo/epidemiologíaRESUMEN
BACKGROUND: Gestational weight gain (GWG) is an important indicator for monitoring maternal and fetal health. OBJECTIVE: To evaluate the effect of GWG outside the recommendations of the Institute of Medicine (IOM) on fetal and neonatal outcomes. STUDY DESIGN: A prospective cohort study with 1642 pregnant women selected from 2017 to 2023, with gestational age ≤ 18 weeks and followed until delivery in the city of Araraquara, Southeast Brazil. The relationship between IOM-recommended GWG and fetal outcomes (abdominal subcutaneous tissue thickness, arm and thigh subcutaneous tissue area and intrauterine growth restriction) and neonatal outcomes (percentage of fat mass, fat-free mass, birth weight and length, ponderal index, weight adequateness for gestational age by the Intergrowth curve, prematurity, and Apgar score) were investigated. Generalized Estimating Equations were used. RESULTS: GWG below the IOM recommendations was associated with increased risks of intrauterine growth restriction (IUGR) (aOR 1.61; 95% CI: 1.14-2.27), low birth weight (aOR 2.44; 95% CI: 1.85-3.21), and prematurity (aOR 2.35; 95% CI: 1.81-3.05), and lower chance of being Large for Gestational Age (LGA) (aOR 0.38; 95% CI: 0.28-0.54), with smaller arm subcutaneous tissue area (AST) (-7.99 g; 95% CI: -8.97 to -7.02), birth length (-0.76 cm; 95% CI: -1.03 to -0.49), and neonatal fat mass percentage (-0.85%; 95% CI: -1.12 to -0.58). Conversely, exceeding GWG guidelines increased the likelihood of LGA (aOR 1.53; 95% CI: 1.20-1.96), with lower 5th-minute Apgar score (aOR 0.42; 95% CI: 0.20-0.87), and increased birth weight (90.14 g; 95% CI: 53.30 to 126.99). CONCLUSION: Adherence to GWG recommendations is crucial, with deviations negatively impacting fetal health. Effective weight control strategies are imperative.
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Retardo del Crecimiento Fetal , Ganancia de Peso Gestacional , Humanos , Femenino , Embarazo , Adulto , Recién Nacido , Estudios Prospectivos , Brasil/epidemiología , Retardo del Crecimiento Fetal/epidemiología , Resultado del Embarazo/epidemiología , Peso al Nacer , Recién Nacido de Bajo Peso , Nacimiento Prematuro/epidemiología , Adulto Joven , Estudios de Cohortes , Edad GestacionalRESUMEN
Introduction: Violence during pregnancy (VDP) is a prevalent global issue with dire consequences for the mother and the developing fetus. These consequences include prematurity, low birthweight, and intrauterine growth restriction (IUGR), but its pathways remain elusive. This study investigated the causal pathways between VDP and IUGR using mediation analysis. Methods: A prospective population-based birth cohort was followed from the beginning of the third gestational trimester to the second year of life. IUGR was defined by the Kramer index, and information on VDP was collected using the WHO-Violence Against Women (WHO VAW) questionnaire. Cases were considered positive only when no other life episodes were reported. Ten different mediators were analyzed as possible pathways based on previous research. Path analysis was conducted to evaluate these relationships. Results: The path analysis model included 755 dyads and presented an adequate fit. Violence during pregnancy showed a direct effect (ß = -0.195, p = 0.041) and a total effect (ß = -0.276, p = 0.003) on IUGR. Violence was associated with gestational depression or anxiety, tobacco and alcohol consumption, changes in blood pressure, and the need for emergency care, but these did not constitute mediators of its effect on IUGR. The sum of the indirect effects, however, showed a significant association with IUGR (ß = -0.081, p = 0.011). Conclusion: The acute experience of violence during pregnancy was associated with IUGR, primarily via a direct pathway. An indirect effect was also present but not mediated through the variables analyzed in this study. The robust strength of these associations underscores the negative health consequences of violence against women for the succeeding generation.
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Retardo del Crecimiento Fetal , Humanos , Femenino , Embarazo , Retardo del Crecimiento Fetal/epidemiología , Adulto , Estudios Prospectivos , Encuestas y Cuestionarios , Estudios de Cohortes , Violencia/psicología , Violencia/estadística & datos numéricos , Recién Nacido , Factores de Riesgo , Análisis de Mediación , Complicaciones del Embarazo/psicología , Complicaciones del Embarazo/epidemiologíaRESUMEN
Poor fetal growth affects eating behavior and the mesocorticolimbic system; however, its influence on the hippocampus has been less explored. Brain insulin sensitivity has been linked to developmental plasticity in response to fetal adversity and to cognitive performance following high-fat diet intake. We investigated whether poor fetal growth and exposure to chronic hyperpalatable food in adulthood could influence the recognition of environmental and food cues, eating behavior patterns, and hippocampal insulin signaling. At 60 days of life, we assigned male offspring from a prenatal animal model of 50% food restriction (FR) to receive either a high-fat and -sugar (HFS) diet or standard chow (CON) diet. Behavioral tests were conducted at 140 days, then tissues were collected. HFS groups showed a diminished hippocampal pAkt/Akt ratio. FR-CON and FR-HFS groups had higher levels of suppressor of cytokine signaling 3, compared to control groups. FR groups showed increased exploration of a novel hyperpalatable food, independent of their diet, and HFS groups exhibited overall lower entropy (less random, more predictable eating behavior) when the environment changed. Poor fetal growth and chronic HFS diet in adulthood altered hippocampal insulin signaling and eating patterns, diminishing the flexibility associated with eating behavior in response to extrinsic changes in food availability in the environment.
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Conducta Alimentaria , Retardo del Crecimiento Fetal , Embarazo , Femenino , Humanos , Ratas , Animales , Masculino , Ratas Sprague-Dawley , Hipocampo , Dieta Alta en Grasa , Insulina , Desarrollo FetalRESUMEN
OBJECTIVES: To identify predictors of outcomes in severe twin oligo-polyhydramnios sequence (TOPS) with or without twin anemia-polycythemia sequence (TAPS) and/or selective fetal growth restriction (SFGR) treated by laser ablation of placental vessels (LAPV). METHODS: Analysis of cases treated from 2011 to 2022. Variables evaluated Prenatal predictors: stages of TOPS, presence of TAPS and/or SFGR; pre-LAPV fetal ultrasound parameters; peri-LAPV variables. Perinatal predictors: GA at birth; birthweight; Apgar scores; transfontanellar ultrasonography (TFUS). OUTCOME VARIABLES: fetal death, neonatal survival, infant's neurodevelopment. Binary logistic regression analyses were performed to detect predictors of outcomes. RESULTS: 265 cases were included. Predictors of post-LAPV donor fetus' death were delta EFW (p:0.045) and absent/reverse end-diastolic flow in the umbilical artery (AREDF-UA) (p < 0.001). The predictor of post-LAPV recipient fetus' death was hydrops (p:0.009). Predictors of neonatal survival were GA at birth and Apgar scores. Predictors of infant's neurodevelopment were TFUS and pre-LAPV middle cerebral artery Doppler (MCAD) for the donor twin; and pre-LAPV ductus venosus' flow and MCAD for the recipient twin. CONCLUSIONS: Prediction of fetal death, neonatal survival and infant's neurodevelopment is possible in cases of TOPS associated or not with SFGR and/or TAPS that were treated by LAPV.
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Transfusión Feto-Fetal , Terapia por Láser , Muerte Perinatal , Polihidramnios , Recién Nacido , Embarazo , Femenino , Humanos , Transfusión Feto-Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/cirugía , Placenta/diagnóstico por imagen , Placenta/cirugía , Placenta/irrigación sanguínea , Muerte Fetal/etiología , Gemelos Monocigóticos , Ultrasonografía Prenatal , Retardo del Crecimiento Fetal , Embarazo Gemelar , Estudios RetrospectivosRESUMEN
OBJECTIVE: To estimate the prevalence and risk of stillbirths by biologic vulnerability phenotypes in a cohort of pregnant women in the municipality of São Paulo, Brazil, 2017-2019. METHODS: Retrospective population-based cohort study. Fetuses were assessed as small for gestational age (SGA), large for gestational age (LGA), adequate for gestational age (AGA), preterm (PT) as less than 37 weeks of gestation, non-PT (NPT) as 37 weeks of gestation or more, low birth weight (LBW) as less than 2500 g, and non-LBW (NLBW) as 2500 g or more. Relative risks (RR) with robust variance were estimated using Poisson regression. RESULTS: In all 442 782 pregnancies, including 2321 (0.5%) stillbirths, were included. About 85% (n = 1983) of stillbirths had at least one characteristic of vulnerability, compared with 21% (n = 92524) of live births. Fetuses with all three markers of vulnerability had the highest adjusted RR of stillbirth-SGA + LBW + PT (RR 155.00; 95% confidence interval [CI] 136.29-176.30) and LGA + LBW + PT (RR 262.04; 95% CI 206.10-333.16) when compared with AGA + NLBW + NPT. CONCLUSION: Our findings show that the simultaneous presence of prematurity, low birth weight, and abnormal intrauterine growth presented a higher risk of stillbirths. To accelerate progress towards reducing preventable stillbirths, one must identify the circumstances of greatest biologic vulnerability.
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Productos Biológicos , Mortinato , Recién Nacido , Femenino , Embarazo , Humanos , Mortinato/epidemiología , Peso al Nacer , Estudios Retrospectivos , Estudios de Cohortes , Brasil/epidemiología , Prevalencia , Recién Nacido Pequeño para la Edad Gestacional , Retardo del Crecimiento Fetal , Edad GestacionalRESUMEN
The composition and diversity of the gut microbiota are essential for the health and development of the immune system of infants. However, there is limited information on factors that influence the gut microbiota of very preterm infants. In this study, we analyzed factors that affect the gut microbiota of very preterm infants. The stool samples from 64 very preterm infants with a gestational age less than 32 weeks were collected for 16S rRNA gene sequencing. The infants were divided according to the delivery mode, antibiotic use during pregnancy, and feeding methods. The abundance of Proteobacteria was high in both cesarean (92.7%) and spontaneous (55.5%) delivery groups and then shifted to Firmicutes after the first week of birth. In addition, Proteobacteria was also the dominant phylum of infant gut microbiome for mothers with antibiotic use, with more than 50% after the first week of birth. In comparison, the dominant phylum for mothers without antibiotic use was Firmicutes. Proteobacteria level was also high in breastfeeding and mixed-feeding groups, consisting of more than 90% of the community. By contrast, Proteobacteria was the dominant phylum at the first week of birth but then shifted to Firmicutes for the formula-fed group. The alterations of gut microbiota in infants can affect their health condition during growth. This study confirmed that the different feeding types, delivery modes, and use of antibiotics during pregnancy can significantly affect the composition of the gut microbiota of very preterm infants.
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Microbioma Gastrointestinal , Lactante , Femenino , Embarazo , Humanos , Recién Nacido , Recien Nacido Prematuro , ARN Ribosómico 16S/genética , Lactancia Materna , Retardo del Crecimiento Fetal , Antibacterianos , HecesRESUMEN
Insults caused by acute infections during the gestational period on fetal development are known; however, new evidence suggests that chronic infectious diseases can also impact the maternal immune status and lead to negative consequences for the neonate. This study investigated the association between the prevalence of specific antibodies in pregnant women and alterations in fetal development at birth. A follow-up study evaluated women during the gestational period and their respective newborns at delivery time. The pregnant women were tested for the presence of antibodies to infectious agents: Toxoplasma gondii (T. gondii), cytomegalovirus (CMV), syphilis, human immunodeficiency virus (HIV), hepatitis B and C. Semi-structured questionnaires were administered to the pregnant women at the time of recruitment after obtaining informed consent. Detailed information about the newborns was extracted from medical records. The seroprevalence of chronic T. gondii infection, as determined by the presence of IgG antibodies against the protozoan, was found to be 56.2%, while the overall prevalence of CMV IgG antibodies was 96.3%. Non-primiparous pregnant women from socio-economic classes, less affluent groups, and skilled working-class individuals had higher chances of testing positive for specific T. gondii IgG antibodies. Newborns classified as small for gestational age represented 12.9% of the total. Those born to mothers seropositive for anti-T. gondii IgG antibodies were 9.4 times more likely to be born small for gestational age (p = 0.035). The results suggest that chronic T. gondii infection may contribute to higher rates of newborns with growth restriction. These findings add to a growing body of evidence regarding the impact of chronic infectious diseases on intrauterine fetal development.
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Infecciones por Citomegalovirus , Hepatitis B , Toxoplasma , Toxoplasmosis , Femenino , Embarazo , Recién Nacido , Humanos , Retardo del Crecimiento Fetal/epidemiología , Estudios Seroepidemiológicos , Estudios de Seguimiento , Inmunoglobulina M , Toxoplasmosis/epidemiología , Anticuerpos Antiprotozoarios , Inmunoglobulina G , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Factores de RiesgoRESUMEN
La deficiencia de zinc puede ser un factor mediador en los trastornos del crecimiento fetal en la descendencia de la gestante diabética. Se persiguió como objetivo determinar la influencia de un suplemento con zinc sobre la morfometría externa corporal y craneofacial en fetos de ratas diabéticas con hiperglucemias moderadas. Durante la gestación, ratas diabéticas y controles fueron suplementadas por vía oral con sulfato de zinc (50 mg/kg-pc) o no recibieron tratamiento. Los fetos descendientes del grupo diabético suplementado presentaron niveles similares a los controles en las variables de crecimiento somático determinadas. La suplementación con zinc a ratas diabéticas favoreció el crecimiento intrauterino en los fetos. Los resultados de esta investigación constituyen aportes para dilucidar los requerimientos de zinc que permitan prevenir los trastornos del crecimiento fetal en la descendencia de gestantes diabéticas.
Zinc deficiency may be a mediating factor in fetal growth disorders in the offspring of diabetic pregnant women. The objective was to determine the influence of a zinc supplement on external body and craniofacial morphometry in diabetic rat fetuses with moderate hyperglycemia. During gestation, diabetic and control rats were orally supplemented with zinc sulphate (50 mg/kg bw) or received no treatment. The fetuses descendants of the supplemented diabetic group had levels similar to the control ones in the determined somatic growth variables. Zinc supplementation to diabetic rats favoured intrauterine growth in fetuses. The results of this research constitute a contribution to elucidate zinc requirements that allow preventing fetal growth disorders in the offspring of diabetic pregnant women.
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Diabetes Mellitus Experimental , Zinc , Retardo del Crecimiento FetalRESUMEN
OBJECTIVE: Pregnancy in women with lupus poses a higher risk of complications compared with the general population. The present study aimed to determine and describe the obstetric and neonatal outcomes of pregnant women with lupus. MATERIALS AND METHODS: We conducted an observational retrospective study of pregnant women with the diagnosis of lupus, who were selected and followed at the Maternal-Fetal Medicine Clinic of our institution between January 2013 and July 2018. We analyzed 59 pregnancies and 52 newborns, and collected data regarding sociodemographic features, the preconception period, pregnancy, childbirth, postpartum and the newborn. A descriptive analysis of the variables was performed. RESULTS: In 58% of the cases, the pregnancy was uneventful. We registered flares in 25% of the cases, preeclampsia in 3%, fetal growth restriction in 12%, gestational loss in 10%, preterm labor in 10%, postpartum complications in 20%, and small for gestational age newborns in 17% of the cases. CONCLUSIONS: Most pregnancies in women with lupus have favorable obstetric and neonatal outcomes. Prenatal counseling, adequate multidisciplinary surveillance, and optimized treatment of the disease are fundamental pillars for these good results.
OBJETIVO: A gravidez em mulheres com lúpus representa um risco maior de complicações em comparação com a população em geral. O presente estudo teve como objetivo determinar e descrever os resultados obstétricos e neonatais de gestantes com lúpus. MATERIAIS E MéTODOS: Realizamos um estudo retrospectivo observacional de gestantes com diagnóstico de lúpus, selecionadas e acompanhadas no Ambulatório de Medicina Materno-Fetal de nossa instituição entre janeiro de 2013 e julho de 2018. Analisamos 59 gestações e 52 recém-nascidos e coletamos dados referentes às características sociodemográficas, período pré-concepcional, gravidez, parto, pós-parto e nascimento. Foi realizada uma análise descritiva das variáveis. RESULTADOS: Em 58% dos casos, a gravidez transcorreu sem intercorrências. Registramos surtos em 25% dos casos, pré-eclâmpsia em 3%, restrição do crescimento fetal em 12%, perda gestacional em 10%, trabalho de parto prematuro em 10%, complicações pós-parto em 20% e recém-nascidos pequenos para a idade gestacional em 17% dos casos. CONCLUSõES: A maioria das gestações em mulheres com lúpus tem resultados obstétricos e neonatais favoráveis. Aconselhamento pré-natal, vigilância multidisciplinar adequada e tratamento otimizado da doença são pilares fundamentais para esses bons resultados.