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OBJECTIVE: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. STUDY DESIGN: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. RESULTS: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with ß-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (ß-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886). CONCLUSIONS: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.
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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 , Epigênese Genética , Retardo do Crescimento Fetal , Sulfeto de Hidrogênio , Hipóxia , Animais , Sulfeto de Hidrogênio/metabolismo , Acetilcisteína/farmacologia , Embrião de Galinha , Humanos , Feminino , Gravidez , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Metilação de DNA , Cistationina gama-Liase/genética , Cistationina gama-Liase/metabolismo , Vasodilatação/efeitos dos fármacos , Placenta/metabolismo , Placenta/irrigação sanguínea , Artérias Umbilicais/metabolismoRESUMO
Maternal Zika virus (ZIKV) infection during pregnancy has been associated with severe intrauterine growth restriction (IUGR), placental damage, metabolism disturbances, and newborn neurological abnormalities. Here, we investigated the impact of maternal ZIKV infection on placental nutrient transporters and nutrient-sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (103 PFU-ZIKVPE243) or High (5 × 107 PFU-ZIKVPE243) ZIKV titers at gestational day (GD) 12.5, and tissue was collected at GD18.5 (term). Fetal-placental growth was impaired in male fetuses, which exhibited higher placental expression of the ZIKV infective marker, eukaryotic translation initiation factor 2 (eIF2α), but lower levels of phospho-eIF2α. There were no differences in fetal-placental growth in female fetuses, which exhibited no significant alterations in placental ZIKV infective markers. Furthermore, ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose-6-phosphate in female placentae, with no differences in amino acid transport potential. In contrast, ZIKV did not impact glucose transporters in male placentae but downregulated sodium-coupled neutral amino acid 2 (Snat2) transporter expression. We also observed sex-dependent differences in the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation in ZIKV-infected pregnancies, showing that ZIKV can disturb placental nutrient sensing. Our findings highlight molecular alterations in the placenta caused by maternal ZIKV infection, shedding light on nutrient transport, sensing, and availability. Our results also suggest that female and male placentae employ distinct coping mechanisms in response to ZIKV-induced metabolic changes, providing insights into therapeutic approaches for congenital Zika syndrome.
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Desenvolvimento Fetal , Camundongos Endogâmicos C57BL , Placenta , Transdução de Sinais , Infecção por Zika virus , Zika virus , Animais , Feminino , Infecção por Zika virus/metabolismo , Infecção por Zika virus/virologia , Gravidez , Camundongos , Placenta/metabolismo , Placenta/virologia , Masculino , Desenvolvimento Fetal/fisiologia , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/metabolismo , Nutrientes/metabolismo , Transportador de Glucose Tipo 1/metabolismoRESUMO
Fetal growth restriction associated with hypertensive disorders of pregnancy (FGR-HDP) is a prevalent pathology with a higher risk of perinatal morbimortality. In this condition, placental insufficiency and endothelial dysfunction serve key roles. The present prospective cohort study monitored 11 patients with an FGR-HDP and 15 with full-term normotensive pregnancies and studied post-natal intracellular calcium concentration ([Ca2+]i) signals in human umbilical vein endothelial cells (HUVECs). Small fetuses with placental insufficiency were identified using fetal biometry with Doppler velocimetry. Mean gestational age and birth weight were 31.8±4.1 weeks and 1,260±646 g for FGR-HDP and 39.2±0.8 weeks and 3,320±336 g for normal births, respectively. Abnormal umbilical artery Doppler waveforms were found in 64% of neonates with FGR-HDP. A significant percentage (86%) of FGR newborns were admitted to the neonatal intensive care unit at Gustavo Fricke hospital, Viña del Mar, Chile, with one case of death after birth. [Ca2+]i signals were measured by microfluorimetry in Fluo-3-loaded HUVECs from primary cultures. Altered [Ca2+]i signals were observed in HUVECs from FGR-HDP, where the sustained phase of ATP-induced [Ca2+]i responses was significantly reduced compared with the normotensive group. Also, the [Ca2+]i signals induced with 10 mM Ca2+ after depletion of internal Ca2+ stores were significantly higher. The present study provides a better comprehension of the role of altered cytosolic Ca2+ dynamics in endothelial dysfunction and an in vitro model to assess novel therapeutic approaches for decreasing or preventing complications in FGR-HDP.
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BACKGROUND: Prematurity is considered to be the leading cause of death in children under 5 years of age, with one child dying every 2 s. Smoking is known to be one of the factors associated with prematurity, with both immediate and late consequences. However, it is difficult to obtain concrete data on the relationship between smoking and spontaneous preterm birth. OBJECTIVE: The aim of this study was to evaluate the influence of active and passive smoking on spontaneous preterm birth. METHODS: This was a multicenter, cross-sectional complementary study that included data on preterm births in 20 maternity hospitals in Brazil between 2011 and 2012. The relationship between smoking category (people who smoke [PWS]; people who smoke indirectly [PWSI]; and people who do not smoke [PWDNS]) and sociodemographic characteristics, birth, and neonatal data was assessed. Statistical analysis was performed using frequencies, percentages, the χ2 test, and stepwise comparisons, with a significance level of 5%. RESULTS: The original study included 5295 pregnant participants and their preterm infants. There were 1491 spontaneous preterm births (SPBs); 1191 preterm rupture of membranes; 1468 therapeutic preterm births; and 1146 term births. The proportion of women who were PWS during pregnancy was 13.5%, and 31.6% were PWSI. Pregnant individuals who smoked and who smoked indirectly had a higher incidence of SPBs (61.2%) compared with PWDNS (48.4%; P < 0.0001); however, multivariate analysis did not confirm causality. CONCLUSIONS: This study did not confirm that smoking during pregnancy increases the risk of SPB. PWSI also did not have an increased incidence of spontaneous preterm birth or adverse neonatal outcomes.
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Nascimento Prematuro , Fumar , Poluição por Fumaça de Tabaco , Humanos , Feminino , Nascimento Prematuro/epidemiologia , Gravidez , Estudos Transversais , Brasil/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Recém-Nascido , Fumar/epidemiologia , Fumar/efeitos adversos , Adulto Jovem , Fatores de Risco , Ruptura Prematura de Membranas Fetais/epidemiologiaRESUMO
SUMMARY 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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Objective: To compare neonatal outcomes in pregnancies with fetal growth restriction (FGR) by intended delivery mode.Methods: This is a retrospective cohort study of singleton pregnancies with FGR that were delivered ≥34.0 weeks gestation. Neonatal outcomes were compared according to the intended delivery mode, which the attending obstetrician determined. Of note, none of the subjects had a contraindication to labor. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between intended delivery mode and neonatal morbidity defined as a composite outcome (i.e. umbilical artery pH ≤7.1, 5-min Apgar score ≤7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). A sensitivity analysis excluded intrapartum fetal distress requiring emergency cesarean delivery from the composite outcome since only patients with spontaneous labor or labor induction could meet this criterion. Potential confounders in the adjusted effects models included maternal age, body mass index, hypertensive disorders, diabetes, FGR type (i.e. early or late), and oligohydramnios.Results: Seventy-two (34%) patients had an elective cesarean delivery, 73 (34%) had spontaneous labor and were expected to deliver vaginally, and 67 (32%) underwent labor induction. The composite outcome was observed in 65.3%, 89%, and 88.1% of the groups mentioned above, respectively (p < 0.001). Among patients with spontaneous labor and those scheduled for labor induction, 63% and 47.8% required an emergency cesarean delivery for intrapartum fetal distress. Compared to elective cesarean delivery, spontaneous labor (OR 4.32 [95% CI 1.79, 10.42], p = 0.001; aOR 4.85 [95% CI 1.85, 12.66], p = 0.001), and labor induction (OR 3.92 [95% CI 1.62, 9.49] p = 0.002; aOR 5.29 [95% CI 2.01, 13.87], p = 0.001) had higher odds of adverse neonatal outcomes.Conclusion: In this cohort of FGR, delivering at ≥34 weeks of gestation, pregnancies with spontaneous labor, and those that underwent labor induction had higher odds of neonatal morbidity than elective cesarean delivery.
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Retardo do Crescimento Fetal , Trabalho de Parto , Gravidez , Recém-Nascido , Feminino , Humanos , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/etiologia , Estudos Retrospectivos , Sofrimento Fetal/epidemiologia , Sofrimento Fetal/etiologia , Cesárea/efeitos adversos , Trabalho de Parto Induzido/efeitos adversos , Idade GestacionalRESUMO
INTRODUCTION: There are many studies showing that silicone breast implants may affect lactation, but few analyzed whether these implants affect placentation. We observed that many mothers with growth-restricted pregnancies had inflammatory conditions, such as silicone breast implants or giardiasis. METHODS: This single-center cohort study assessed the prevalence of inflammatory conditions in normotensive growth-restricted singleton pregnancies. Next, we stratified the patients according to the presence or absence of silicone breast implants, to determine whether these implants influence fetal growth restriction onset or severity. RESULTS: Twelve (32%) of the 38 participants underwent cosmetic breast augmentation 4-18 years before pregnancy. Half of the patients with and 38% without silicone breast implants had giardiasis. Half of the mothers with and 35% without silicone breast implants had autoantibodies. Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32 weeks' gestation (95% confidence interval [CI], 1.2-2.5). Fetal growth restriction was diagnosed significantly earlier in mothers with than in those without silicone breast implants, respectively at 27 (95% CI, 25-30) and 30 weeks' gestation (95% CI, 29-32). Silicone breast implants also tripled the risk of fetuses being below the third percentile, but the difference was not significant. CONCLUSION: Our results suggest that the association of inflammatory conditions, such as silicone breast implants, giardiasis, and autoantibodies may contribute to placental insufficiency. Silicone breast implants older than four years increased the risk of early-onset fetal growth restriction. Studies with large samples are needed to validate our findings and define whether silicone-related fetal growth restriction should be included in autoimmune/inflammatory syndrome induced by adjuvants (ASIA) criteria. Key Points ⢠Fetal growth restriction (FGR), responsible for 30% of stillbirths, is the most common cause of prematurity and intrapartum asphyxia. ⢠In this study, including 38 mothers with normotensive FGR, all participants had 2-4 inflammatory conditions, such as giardiasis, sinusitis, candidiasis, dysbiosis, extreme fear or autoantibodies. ⢠Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32 weeks' gestation. ⢠FGR was diagnosed at 27 weeks' gestation (95% CI, 25-30) in mothers with and at 30 weeks' gestation (95% CI, 29-32) in mothers without silicone breast implants.
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Implantes de Mama , Giardíase , Gravidez , Humanos , Feminino , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/diagnóstico , Estudos de Coortes , Implantes de Mama/efeitos adversos , PlacentaRESUMO
OBJECTIVES: To evaluate the prevalence and perinatal repercussions of preeclampsia (PE) after the implementation of a prophylaxis protocol with aspirin in singleton pregnancy at Maternity School of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2015-2106). METHODOLOGY: PE prevalence according to gestational age (GA) and the prevalence ratio (PR) between PE and prematurity, small for gestational age (SGA), and fetal death were calculated in patients assisted during 2015 and 2016. RESULTS: PE occurred in 373(10.75%) of 3468 investigated cases, where PE < 37 weeks was of 2.79% and PE greater than 37 weeks was of 7.95%. A total of 413 (11.9%) prematurity cases, 320 SGA (9.22%), and 50 fetal deaths (1.44%) occurred. In the PE group, 97 premature newborns (PR 0.90) and 51 SGA (PR 1.16) were born, and two fetal deaths occurred (PR 7.46). Concerning PE < 37 weeks, 27 SGA cases (PR 1.42) and two fetal deaths (PR 2.62) were observed. Regarding PE greater than 37 weeks, 24 SGA (PR 1.09) were born, and no fetal deaths were observed. Our findings were compared to previously published results. CONCLUSIONS: PE was significantly associated with SGA newborns, especially premature PE. Prescribing aspirin for PE prophylaxis based only on clinical risk factors in a real-life scenario does not appear to be effective but resulted in a PE screening and prophylaxis protocol review and update at ME/UFRJ.
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Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Recém-Nascido , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/diagnóstico , Aspirina/uso terapêutico , Prevalência , Brasil , Recém-Nascido Pequeno para a Idade Gestacional , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/prevenção & controle , Retardo do Crescimento Fetal/diagnóstico , Morte Fetal/prevenção & controle , Idade GestacionalRESUMO
Abstract Objective: To assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR). Methods: This prospective cross-sectional study included pregnant women with gestational age between 26 and 37 + 6 weeks with FGR and appropriate for gestational age (AGA) fetuses. The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were measured using centrifugation and liquid chromatography. The Student's t-test, Mann-Whitney test, and general linear model, with gestational age and maternal weight as covariants, were used to compare FA levels and the FGR and AGA groups. The Chi-square was used to evaluate the association between groups and studied variables. Results: Maternal blood sample was collected from 64 pregnant women, being 24 FGR and 40 AGA. A weak positive correlation was found between the palmitoleic acid level and maternal weight (r = 0.285, p = 0.036). A weak negative correlation was found between the gamma-linoleic acid level and gestational age (r = −0.277, p = 0.026). The median of the elaidic acid level (2.3 vs. 4.7ng/ml, p = 0.045) and gamma-linoleic acid (6.3 vs. 6.6ng/ml, p = 0.024) was significantly lower in the FGR than the AGA group. The palmitoleic acid level was significantly higher in the FGR than AGA group (50.5 vs. 47.6ng/ml, p = 0.033). Conclusion: Pregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.
Resumo Objetivo: Avaliar os níveis sanguíneos maternos de ácidos graxos (AGs) em gestações com restrição de crescimento fetal (RCF). Métodos: Este estudo prospectivo transversal incluiu gestantes com idade gestacional entre 26 e 37 semanas e 6 dias com RCF e fetos adequados para a idade gestacional (AIG). Os níveis de ácidos graxos saturados, trans, monoinsaturados e poliinsaturados foram medidos usando centrifugação e cromatografia líquida. O teste t-Student, o teste de Mann-Whitney e o modelo linear geral, com idade gestacional e peso materno como covariantes, foram utilizados para comparar os níveis de AGs e os grupos RCF e AIG. O teste Qui-quadrado foi utilizado para avaliar a associação entre os grupos e as variáveis estudadas. Resultados: Amostra de sangue materno foi coletada de 64 gestantes, sendo 24 RCF e 40 AIG. Uma correlação positiva fraca foi encontrada entre o nível de ácido palmitoleico e o peso materno (r = 0,285, p = 0,036). Uma correlação negativa fraca foi encontrada entre o nível de ácido gama-linoleico ea idade gestacional (r = −0,277, p = 0,026). A mediana do nível de ácido elaídico (2,3 vs. 4,7 ng/ml, p = 0,045) e ácido gama-linoleico (6,3 vs. 6,6 ng/ml, p = 0,024) foram significativamente menores no grupo RCF do que no grupo AIG. O nível de ácido palmitoleico foi significativamente maior no grupo RCF do que no grupo AIG (50,5 vs. 47,6 ng/ml, p = 0,033). Conclusão: Gestantes com RCF apresentaram níveis mais baixos de ácido elaídico e ácido gama-linoleico e níveis mais elevados de ácido palmitoleico do que os fetos AIG.
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Humanos , Feminino , Gravidez , Ácidos Graxos , Retardo do Crescimento FetalRESUMO
Abstract This comprehensive review compares clinical protocols of important entities regarding the management of fetal growth restriction (FGR), published since 2015. Five protocols were chosen for data extraction. There were no relevant differences regarding the diagnosis and classification of FGR between the protocols. In general, all protocols suggest that the assessment of fetal vitality must be performed in a multimodally, associating biophysical parameters (such as cardiotocography and fetal biophysical profile) with the Doppler velocimetry parameters of the umbilical artery, middle cerebral artery, and ductus venosus. All protocols reinforce that the more severe the fetal condition, the more frequent this assessment should be made. The timely gestational age and mode of delivery to terminate the pregnancy in these cases can vary much between the protocols. Therefore, this paper presents, in a didactic way, the particularities of different protocols for monitoring FGR, in order to help obstetricians to better manage the cases.
Resumo Esta revisão compreensiva compara protocolos clínicos de entidades importantes em relação ao manejo da restrição de crescimento fetal (RCF), publicados desde 2015. Cinco protocolos foram escolhidos para a extração de dados. Não houve diferenças relevantes quanto ao diagnóstico e classificação da RCF entre os protocolos. Em geral, todos os protocolos sugerem que a avaliação da vitalidade fetal deve ser realizada de forma multimodal, associando parâmetros biofísicos (como cardiotocografia e perfil biofísico fetal) aos parâmetros dopplervelocimétricos da artéria umbilical, artéria cerebral média e ducto venoso. Todos os protocolos reforçam que quanto mais grave a condição fetal, mais frequente essa avaliação deve ser feita. A idade gestacional oportuna e o modo de parto para interromper a gravidez nesses casos podem variar muito entre os protocolos. Portanto, este trabalho apresenta, de forma didática, as particularidades de diferentes protocolos de acompanhamento de RCF, a fim de auxiliar os obstetras no melhor manejo dos casos.
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Humanos , Recém-Nascido , Recém-Nascido Prematuro , Cardiotocografia , Fluxometria por Laser-Doppler , Guias como Assunto , Retardo do Crescimento FetalRESUMO
OBJECTIVE: To evaluate the performance of INTERGROWTH-21st (IG-21st ) and World Health Organization (WHO) fetal growth charts to identify small-for-gestational-age (SGA) and fetal growth restriction (FGR) neonates, as well as their specific risks for adverse neonatal outcomes. METHODS: Multicenter cross-sectional study including 67 968 live births from 10 maternity units across four Latin American countries. According to each standard, neonates were classified as SGA and FGR (birth weight <10th and less than third centiles, respectively). The relative risk (RR) and diagnostic performance for a low APGAR score and low ponderal index were calculated for each standard. RESULTS: WHO charts identified more neonates as SGA than IG-21st (13.9% vs 7%, respectively). Neonates classified as having FGR by both standards had the highest RR for a low APGAR (RR, 5.57 [95% confidence interval (CI), 3.99-7.78]), followed by those who were SGA by both curves (RR, 3.27 [95% CI, 2.52-4.24]), while neonates with SGA identified by WHO alone did not have an additional risk (RR, 0.87 [95% CI, 0.55-1.39]). Furthermore, the diagnostic odds ratio for a low APGAR was higher when IG-21st was used. CONCLUSION: In a population from Latin America, the WHO charts seem to identify more SGA neonates, but the diagnostic performance of the IG-21st charts for low APGAR score and low ponderal index is better.
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Retardo do Crescimento Fetal , Gráficos de Crescimento , Recém-Nascido , Gravidez , Feminino , Humanos , Retardo do Crescimento Fetal/diagnóstico , América Latina , Idade Gestacional , Estudos Transversais , Recém-Nascido Pequeno para a Idade Gestacional , Peso ao Nascer , Ultrassonografia Pré-NatalRESUMO
During pregnancy, the body undergoes a great amount of changes in order to support a healthy developing fetus. In this context, maternal dietary supplementation is widely encouraged to provide adequate nutrition for the newborn. In the past few years, studies have emerged highlighting the benefits of polyphenols intake during pregnancy. Indeed, despite differences among reports, such as experimental model, polyphenol employed, dosage and regimen of administration, there is no doubt that the ingestion of these molecules has a protective effect in relation to three pregnancy-associated diseases or conditions: preeclampsia, gestational diabetes and fetal growth restriction. In this review, we describe the effects of different polyphenols and polyphenol-rich extracts or juices on the main outcomes of these common pregnancy-associated complications, obtained in human, animal and in vitro studies. Therefore, this work provides a critical analysis of the literature, and a summary of evidences, from which future research using polyphenols can be designed and evaluated.
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SUMMARY OBJECTIVE: The aim of this study was to assess fetal thymus size by ultrasound in growth-restricted fetuses due to placental insufficiency and compare to high-risk and low-risk pregnancy fetuses with normal placental function. METHODS: This is a nested case-control study of pregnant women followed up at a university hospital (July 2012 to July 2013). In all, 30 pregnant women presenting small fetuses for gestational age (estimated fetal weight <p10) due to placental insufficiency (umbilical artery Doppler >p95) were compared to 30 high-risk and 30 low-risk pregnancies presenting normal Doppler indices. The thymus transverse diameter and perimeter were converted into zeta score according to the normal values for gestational age. Head circumference and femur length were used to calculate ratios. RESULTS: Fetal thymus were significantly lower in pregnancies with placental insufficiency when compared to high-risk and low-risk pregnancies presenting, respectively, transverse diameter zeta score (-0.69±0.83 vs. 0.49±1.13 vs. 0.83±0.85, p<0.001) and P zeta score (-0.73±0.68 vs. 0.45±0.96 vs. 0.26±0.89, p<0.001). There was also a significant difference (p<0.05) in the ratios among the groups: pregnancies with placental insufficiency (TD/HC=0.10, P/FL=1.32, and P/HC=0.26), high-risk pregnancies (TD/HC=0.11, P/FL=1.40, and P/HC=0.30), and control group (DT/HC=0.11, P/FL=1.45, and P/HC=0.31). CONCLUSION: Fetal thymus size is reduced in growth-restricted fetuses due to placental insufficiency, suggesting fetal response as a consequence of the adverse environment.
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CCR5 is a chemokine receptor that mediates cell recruitment to sites of inflammation. It has been previously reported that the expression of CCR5 is increased in the placentas of women with malaria, a disease characterized by causing deliveries with low birth weight among other complications. CCR5 has been associated with pathology of protozoan infections during pregnancy but its role during malaria in pregnancy has not been elucidated. In the present work, we assessed the pregnancy outcome, placental structure, and levels of inflammatory markers of pregnant C57BL/6 and CCR5-/- mice infected or not with Plasmodium berghei NK65, with the purpose of determine the role of CCR5 in pregnancy associated malaria complications. We demonstrated that the expression of CCR5 mRNA increases in late pregnancy placentas of C57BL/6 when compared to uninfected controls. Infected pregnant C57BL/6 mice showed preterm birth, decreased fetal weight, placental inefficiency, and reduced placental vascular space. On the other hand, CCR5 deficiency led to increased levels of maternal parasitemia, reduced fetal weight and placental inefficiency compared to C57BL/6 mice. However, the infection did not cause additional changes in these parameters or in the incidence of preterm delivery in infected CCR5-/- mice in relation to C57BL/6 mice, showing that CCR5 may contribute to the adverse effects caused by infection during pregnancy. This improvement in pregnancy outcome, observed in infected CCR5-/- mice, was accompanied by lower placental levels of the inflammatory markers, such as TNF and NAG. Furthermore, it was observed that the placentas of CCR5-/- animals showed structural differences in relation to C57BL/6 mice, which could improve the efficiency of maternal-fetal exchanges, reflecting on fetal weight. Taken together, these results indicate that CCR5 expression contributes to the adverse outcomes caused by malaria in late pregnancy.
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Malária , Complicações Parasitárias na Gravidez , Complicações na Gravidez , Nascimento Prematuro , Recém-Nascido , Humanos , Gravidez , Feminino , Animais , Camundongos , Placenta/patologia , Peso Fetal , Camundongos Endogâmicos C57BL , Resultado da Gravidez , Receptores CCR5/genéticaRESUMO
PURPOSE: We aim to compare the perinatal outcomes of two consecutive management strategies for fetal growth restriction (FGR), with or without the inclusion of additional Doppler parameters. METHODS: A quasi-experimental before/after study was conducted in which we compared a composite perinatal outcome, prematurity rate, and neonatal complications between two management strategies in small fetuses. In the strategy 1 (S1), the management was based on fetal biometry and umbilical artery Doppler. The second strategy (S2) added the assessment of uterine and middle cerebral artery Doppler. We also compared outcomes between strategies according to early (≤ 32 weeks) and late (> 32 weeks) diagnosis subgroups. RESULTS: We included 396 patients, 163 in S1 and 233 in S2. There were no significant differences in the perinatal composite outcome (p 0.98), prematurity (p 0.19), or in the subgroup analysis. We found a significant reduction in respiratory distress syndrome (RDS) rate with S2 both globally (OR 0.50, p 0.02), and in the early diagnosis subgroup (OR 0.45, p 0.01). In addition, we observed a significant reduction in the incidence of sepsis with S2 both globally (OR 0.30, p 0.04) and in the early diagnosis subgroup (OR 0.25, p 0.02). We did not observe significant differences in necrotizing enterocolitis (p 0.41) and intraventricular hemorrhage (p 1.00). CONCLUSION: The expanded strategy for the management of FGR did not show significant differences in the primary composite outcome or prematurity. However, it was associated with a lower incidence of RDS and neonatal sepsis.
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Retardo do Crescimento Fetal , Feto , Feminino , Gravidez , Humanos , Recém-Nascido , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/epidemiologia , Estudos Controlados Antes e Depois , Feto/irrigação sanguínea , Artéria Cerebral Média/diagnóstico por imagem , Artérias Umbilicais/diagnóstico por imagem , Ultrassonografia Pré-Natal , Ultrassonografia DopplerRESUMO
Resumen ANTECEDENTES: Existe interés creciente en los efectos de la vitamina D en el embarazo y en la función placentaria, homeostasis de la glucosa, infección y respuesta inflamatoria, además de la asociación de su deficiencia con enfermedades de alto riesgo obstétrico. OBJETIVO: Identificar los aspectos relevantes conocidos y controvertidos del déficit de vitamina D y de su suplementación en pacientes con alto riesgo obstétrico que permitan aportarle al lector herramientas para la toma de decisiones en la práctica clínica. METODOLOGÍA: Se llevó a cabo una revisión de la bibliografía registrada en las bases de datos de MEDLINE vía PubMed, EBSCO y OVID del 2016 al 2022. Se consultaron artículos publicados en inglés y español, con los términos MeSH "Vitamin D", "preeclampsia", "premature birth", "diabestes, gestational" y "fetal growth retardation". RESULTADOS: La búsqueda inicial arrojó 685 artículos de los que se descartaron 364 por falta de pertinencia, 248 por falta del recurso completo y 44 por duplicaciones. De acuerdo con el objetivo planteado, al final quedaron 29 artículos que se complementaron con 55 textos clásicos encontrados en una búsqueda manual para contextualización de la revisión. CONCLUSIONES: La evidencia respecto de la asociación entre deficiencia de vitamina D y pobres desenlaces obstétricos, en términos de tasas de preeclampsia, parto pretérmino, diabetes gestacional y restricción del crecimiento fetal no es concluyente. Sin embargo, el análisis de los estudios mencionados muestra una relación entre el déficit de vitamina D y el aumento del riesgo, desenlaces impactantes y consistentes con el riesgo de resultar con diabetes gestacional.
Abstract BACKGROUND: There is increasing interest in the effects of vitamin D in pregnancy and on placental function, glucose homeostasis, infection and inflammatory response, and the association of vitamin D deficiency with high-risk obstetric conditions. OBJECTIVE: To identify the relevant known and controversial aspects of vitamin D deficiency and its supplementation in patients at high obstetric risk, in order to provide the reader with decision-making tools for clinical practice. METHODOLOGY: A review of the literature registered in the MEDLINE databases via PubMed, EBSCO and OVID from 2016 to 2022 was performed. Articles published in English and Spanish were included using the MeSH terms "vitamin D", "pre-eclampsia", "preterm birth", "gestational diabetes" and "fetal growth retardation". RESULTS: The initial search yielded 685 articles, of which 364 were discarded for lack of relevance, 248 for lack of complete source and 44 for duplication. In accordance with the stated objective, 29 articles remained at the end, which were supplemented by 55 classic texts found in a manual search to contextualise the review. CONCLUSIONS: The evidence for an association between vitamin D deficiency and poor obstetric outcomes in terms of rates of pre-eclampsia, preterm birth, gestational diabetes and fetal growth restriction is inconclusive. However, analysis of the above studies shows an association between vitamin D deficiency and increased risk, with striking results consistent with the risk of gestational diabetes.
RESUMO
Introduction: During pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. Important proteins during placentation are known to be targets for O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension. Methods: To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses. Results: SHR presented a higher blood pressure than the Wistar rats (p=0.001). Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs. Conclusions: These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth.
Assuntos
Hipertensão , Placenta , Feminino , Gravidez , Ratos , Masculino , Animais , Placenta/metabolismo , Ratos Wistar , Ratos Endogâmicos SHR , Placentação , NutrientesRESUMO
Objectives: To determine the predictive performance of fetal growth restriction by Maternal Fetal Medicine Society (MFMS) definition of ultrasound, the Delphi consensus (DC) and the Barcelona Fetal Medicine (BFM) criteria for adverse perinatal outcomes, and to identify whether there is an association between the diagnosis of fetal growth restriction (FGR) and adverse perinatal outcomes. Material and methods: A retrospective cohort study was conducted including women with singleton pregnancies between 24 and 36 weeks of gestation seen at the maternal fetal medicine unit for ultrasound assessment of fetal growth and delivery care in a public referral hospital in Popayán, Colombia. Pregnancies with ultrasound findings of congenital abnormalities were excluded. Convenience sampling was used. Sociodemographic and clinical variables were measured on admission; additional variables were gestational age, FGR diagnosis and adverse composite perinatal outcome. The predictive ability of three fetal growth restriction diagnostic criteria for poor perinatal outcomes was analyzed and asociation between FGR and adverse perinatlal outcomes. Results: Overall, 228 pregnant women with a mean age of 26.8 years were included; FGR prevalence according to the three criteria was 3.95 %, 16.6 % and 21.9 % for DC, BFM and MFMS, respectively. None of the criteria resulted in an acceptable area under the curve for the prediction of the composite adverse neonatal outcome; FGR diagnosis by DC and MFMS were associated with adverse perinatal outcomes with a RR of 2.6 (95 % CI: 1.5-4.3) and 1.57 (95 % CI: 1.01-2.44) respectively. No association was found for BFM RR: 1.32 (95 % CI: 0.8-2.1). Conclusions: Given a positive result for FGR, the Delphi method is significantly associated with adverse perinatal outcomes. The proportion of false negative results for a poor perinatal outcome is high for the three methods. Prospective studies that reduce measurement and attrition bias are required.
Objetivos: determinar el desempeño predictivo de la definición de retardo de crecimiento fetal (RCF) de ultrasonografía de la Sociedad de Medicina Materno Fetal (SMMF), consenso Delphi (CD) y Medicina Fetal de Barcelona (MFB) respecto a resultados adversos perinatales en cada una, e identificar si hay asociación entre diagnóstico de RCF y resultados adversos perinatales. Materiales y métodos: se realizó un estudio de cohorte retrospectiva. Se incluyeron gestantes con embarazo único de 24 a 36 semanas con 6 días, quienes fueron atendidas en la unidad de medicina materna fetal con evaluación ecográfica de crecimiento fetal y atención de parto en una institución hospitalaria pública de referencia ubicada en Popayán, Colombia. Se excluyeron embarazos con hallazgos ecográficos de anomalías congénitas. Muestreo por conveniencia. Se midieron variables sociodemográficas y clínicas de las gestantes al ingreso, la edad gestacional, el diagnóstico de RCF y el resultado adverso perinatal compuesto. Se analizó la capacidad predictiva de tres criterios diagnósticos de restricción de crecimiento fetal para malos resultados perinatales y la asociación entre el diagnóstico de RCF y mal resultado periantal. Resultados: se incluyeron 228 gestantes, cuya edad media fue de 26,8 años, la prevalencia de RCF según los tres criterios fue de 3,95 %, 16,6 % y 21,9 % para CD, MFB y SMMF respectivamente. Ningún criterio aportó área bajo la curva aceptable para predicción de resultado neonatal adverso compuesto, el diagnóstico de RCF por CD y SMMF se asoció a resultados adversos perinatales con RR de 2,6 (IC 95 %: 1,5-4,3) y 1,57 (IC 95 %: 1,01-2,44), respectivamente. No se encontró asociación por MFB RR: 1,32 (IC 95 %: 0,8-2,1). Conclusiones: ante un resultado positivo para RCF, el método Delphi se asocia de manera más importante a los resultados perinatales adversos.Los tres métodos tienen una muy alta proporción de falsos negativos en la predicción de mal resultado perinatal. Se requieren estudios prospectivos que reduzcan los sesgos de medición y datos ausentes.
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Retardo do Crescimento Fetal , Hospitais , Colômbia , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
BACKGROUND: Small-for-gestational-age neonates (SGA) are at increased risk of neonatal morbidity. Nulliparity represents a risk factor for SGA; birthweight charts may perform differently for the detection of SGA among nulliparas. This study aimed at describing the prevalence of SGA in nulliparas according to different birthweight charts and evaluating the diagnostic performance of these charts to maternal and perinatal outcomes. METHODS: This is a secondary analysis of a Brazilian cohort of nulliparas named Preterm SAMBA study. Birthweight centiles were calculated using the Intergrowth-21st, WHO-Fetal Growth Charts, Birth in Brazil population chart and GROW-customised chart. The risks of outcomes among SGA neonates and their mothers in comparison to neonates with birthweights between the 40th-60th centiles were calculated, according to each chart. ROC curves were used to detect neonatal morbidity in neonates with birth weights below different cutoff centiles for each chart. RESULTS: A sample of 997 nulliparas was assessed. The rate of SGA infants varied between 7.0-11.6%. All charts showed a significantly lower risk of caesarean sections in women delivering SGA neonates compared to those delivering adequate-for-gestational-age neonates (OR 0.55-0.64, p < .05). The charts had poor performance (AUC 0.492 - 0.522) for the detection of neonatal morbidity related to SGA born at term. CONCLUSION: The populational and customised birthweight charts detected different prevalence of small-for-gestational-age neonates and showed similar and poor performance to identify related neonatal adverse outcomes in this population.