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1.
Ultrasound Obstet Gynecol ; 62(6): 860-866, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37470712

RESUMEN

OBJECTIVES: To use superb microvascular imaging (SMI) to evaluate longitudinally spiral artery (SA) and uterine artery (UtA) vascular adaptation in normal human pregnancy, and to develop reference ranges for use at various gestational ages throughout pregnancy. METHODS: The data for this study were obtained from the National Institutes of Health (NIH)-funded Human Placenta Project. Women aged 18-35 years, with a body mass index < 30 kg/m2 , without comorbidities, with a singleton gestation conceived spontaneously, and gestational age at or less than 13 + 6 weeks were eligible for inclusion. The current analysis was restricted to uncomplicated pregnancies carried to term. Exclusion criteria included maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation or delivery < 37 weeks. Women who fulfilled the inclusion criteria formed the reference population of the Human Placenta Project study. Each participant underwent eight ultrasound examinations during pregnancy. The pulsatility index (PI) of both the left and right UtA were obtained twice for each artery and the presence or absence of a notch was noted. Using SMI technology, the total number of SA imaged was recorded in a sagittal placental section at the level of cord insertion. The PI and peak systolic velocity (PSV) were also measured in a total of six SA, including two in the central portion of the placenta, two peripherally towards the uterine fundal portion, and two peripherally towards the lower uterine segment. RESULTS: A total of 90 women fulfilled the study criteria. Maternal UtA-PI decreased throughout the first half of pregnancy from a mean ± SD of 1.39 ± 0.50 at 12-13 weeks' gestation to 0.88 ± 0.24 at 20-21 weeks' gestation. The mean number of SA visualized in a sagittal plane of the placenta increased from 8.83 ± 2.37 in the first trimester to 16.99 ± 3.31 in the late-third trimester. The mean SA-PI was 0.57 ± 0.12 in the first trimester and decreased progressively during the second trimester, reaching a nadir of 0.40 ± 0.10 at 24-25 weeks, and remaining constant until the end of pregnancy. SA-PSV was highest in early pregnancy with a mean of 57.16 ± 14.84 cm/s at 12-13 weeks' gestation, declined to a mean of 49.38 ± 17.88 cm/s at 20-21 weeks' gestation and continued to trend downward for the remainder of pregnancy, reaching a nadir of 34.50 ± 15.08 cm/s at 36-37 weeks' gestation. A statistically significant correlation was noted between SA-PI and UtA-PI (r = 0.5633; P < 0.001). Multilevel regression models with natural cubic splines were used to create reference ranges of SA-PSV and SA-PI for given gestational ages. CONCLUSION: From early gestation, we have demonstrated the ability to image and quantify SA blood flow in normal pregnancy, and have developed reference ranges for use at various gestational ages throughout pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Preeclampsia , Arteria Uterina , Recién Nacido , Embarazo , Femenino , Humanos , Arteria Uterina/diagnóstico por imagen , Arteria Uterina/fisiología , Placenta/diagnóstico por imagen , Placenta/irrigación sanguínea , Ultrasonografía Prenatal , Ultrasonografía , Tercer Trimestre del Embarazo , Edad Gestacional , Flujo Pulsátil , Preeclampsia/epidemiología
2.
BJOG ; 129(3): 473-483, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34605130

RESUMEN

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.


Asunto(s)
Diabetes Gestacional/tratamiento farmacológico , Prescripciones de Medicamentos/estadística & datos numéricos , Hipoglucemiantes/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Prenatal/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Femenino , Gliburida/uso terapéutico , Humanos , Insulina/uso terapéutico , Metformina/uso terapéutico , Persona de Mediana Edad , Embarazo , Estados Unidos , Adulto Joven
3.
BJOG ; 129(4): 619-626, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34529344

RESUMEN

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.


Asunto(s)
Fructosamina/sangre , Mortinato/epidemiología , Adulto , Estudios de Casos y Controles , Causalidad , Femenino , Humanos , Nacimiento Vivo/epidemiología , Embarazo , Curva ROC , Factores de Riesgo , Estados Unidos/epidemiología
4.
BJOG ; 125(3): 343-350, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28139890

RESUMEN

OBJECTIVE: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB). DESIGN: Case-control. SETTING: Three tertiary-care centres across the USA. POPULATION: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P. METHODS: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P). MAIN OUTCOME MEASURES: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction). CONCLUSION: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P. TWEETABLE ABSTRACT: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment.


Asunto(s)
Caproato de 17 alfa-Hidroxiprogesterona/uso terapéutico , Nacimiento Prematuro , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Farmacogenética , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/genética , Nacimiento Prematuro/prevención & control , Progestinas/uso terapéutico , Recurrencia , Estados Unidos/epidemiología , Secuenciación del Exoma/métodos , Secuenciación del Exoma/estadística & datos numéricos
5.
Ultrasound Obstet Gynecol ; 52(6): 757-762, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29155504

RESUMEN

OBJECTIVE: To evaluate whether the presence of cervical funneling or intra-amniotic debris identified in the second trimester is associated with a higher rate of preterm birth (PTB) in asymptomatic nulliparous pregnant women with a midtrimester cervical length (CL) less than 30 mm (i.e. below the 10th percentile). METHODS: This was a secondary cohort analysis of data from a multicenter trial in nulliparous women between 16 and 22 weeks' gestation with a singleton gestation and CL less than 30 mm on transvaginal ultrasound, randomized to treatment with either 17-alpha-hydroxyprogesterone caproate or placebo. Sonographers were centrally certified in CL measurement, as well as in identification of intra-amniotic debris and cervical funneling. Univariable and multivariable analysis was performed to assess the associations of cervical funneling and intra-amniotic debris with PTB. RESULTS: Of the 657 women randomized, 112 (17%) had cervical funneling only, 33 (5%) had intra-amniotic debris only and 45 (7%) had both on second-trimester ultrasound. Women with either of these findings had a shorter median CL than those without (21.0 mm vs 26.4 mm; P < 0.001). PTB prior to 37 weeks was more likely in women with cervical funneling (37% vs 21%; odds ratio (OR), 2.2 (95% CI, 1.5-3.3)) or intra-amniotic debris (35% vs 23%; OR, 1.7 (95% CI, 1.1-2.9)). Results were similar for PTB before 34 and before 32 weeks' gestation. After multivariable adjustment that included CL, PTB < 34 and < 32 weeks continued to be associated with the presence of intra-amniotic debris (adjusted OR (aOR), 1.85 (95% CI, 1.00-3.44) and aOR, 2.78 (95% CI, 1.42-5.45), respectively), but not cervical funneling (aOR, 1.17 (95% CI, 0.63-2.17) and aOR, 1.45 (95% CI, 0.71-2.96), respectively). CONCLUSIONS: Among asymptomatic nulliparous women with midtrimester CL less than 30 mm, the presence of intra-amniotic debris, but not cervical funneling, is associated with an increased risk for PTB before 34 and 32 weeks' gestation, independently of CL. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Asunto(s)
17-alfa-Hidroxiprogesterona/uso terapéutico , Líquido Amniótico/química , Cuello del Útero/diagnóstico por imagen , Nacimiento Prematuro/epidemiología , Ultrasonografía Prenatal/métodos , Adulto , Medición de Longitud Cervical , Estudios de Cohortes , Femenino , Humanos , Edad Materna , Embarazo , Segundo Trimestre del Embarazo , Nacimiento Prematuro/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto Joven
6.
Ultrasound Obstet Gynecol ; 50(2): 156-166, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27935148

RESUMEN

OBJECTIVE: To compare the effectiveness of customized vs population-based growth charts for the prediction of adverse pregnancy outcomes. METHODS: MEDLINE, ClinicalTrials.gov and The Cochrane Library were searched up to 31 May 2016 to identify interventional and observational studies comparing adverse outcomes among large- (LGA) and small- (SGA) for-gestational-age neonates, when classified according to customized vs population-based growth charts. Perinatal mortality and admission to the neonatal intensive care unit (NICU) of both SGA and LGA neonates, intrauterine fetal demise (IUFD) and neonatal mortality of SGA neonates, and neonatal shoulder dystocia and hypoglycemia as well as maternal third- and fourth-degree perineal lacerations in LGA pregnancies were evaluated. RESULTS: The electronic search identified 237 records that were examined based on title and abstract, of which 27 full-text articles were examined for eligibility. After excluding seven articles, 20 observational studies were included in a Bayesian meta-analysis. Neonates classified as SGA according to customized growth charts had higher risks of IUFD (odds ratio (OR), 7.8 (95% CI, 4.2-12.3)), neonatal death (OR, 3.5 (95% CI, 1.1-8.0)), perinatal death (OR, 5.8 (95% CI, 3.8-7.8)) and NICU admission (OR, 3.6 (95% CI, 2.0-5.5)) than did non-SGA cases. Neonates classified as SGA according to population-based growth charts also had increased risk for adverse outcomes, albeit the point estimates of the pooled ORs were smaller: IUFD (OR, 3.3 (95% CI, 1.9-5.0)), neonatal death (OR, 2.9 (95% CI, 1.2-4.5)), perinatal death (OR, 4.0 (95% CI, 2.8-5.1)) and NICU admission (OR, 2.4 (95% CI, 1.7-3.2)). For LGA vs non-LGA, there were no differences in pooled ORs for perinatal death, NICU admission, hypoglycemia and maternal third- and fourth-degree perineal lacerations when classified according to either the customized or the population-based approach. In contrast, both approaches indicated that LGA neonates are at increased risk for shoulder dystocia than are non-LGA ones (OR, 7.4 (95% CI, 4.9-9.8) using customized charts; OR, 8.0 (95% CI, 5.3-10.1) using population-based charts). CONCLUSIONS: Both customized and population-based growth charts can identify SGA neonates at risk for adverse outcomes. Although the point estimates of the pooled ORs may differ for some outcomes, the overlapping CIs and lack of direct comparisons prevent conclusions from being drawn on the superiority of one method. Future clinical trials should compare directly the two approaches in the management of fetuses of abnormal size. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Asunto(s)
Peso al Nacer , Gráficos de Crecimiento , Recién Nacido Pequeño para la Edad Gestacional/crecimiento & desarrollo , Teorema de Bayes , Femenino , Macrosomía Fetal , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Embarazo , Resultado del Embarazo
7.
J Hum Nutr Diet ; 30(1): 51-58, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27412890

RESUMEN

BACKGROUND: The present study aimed to investigate the association between gestational weight gain (GWG) and birth weight, as well as the body mass index (BMI) status, of children at the ages of 2 and 8 years. METHODS: Population-based data were obtained from a database of all 7-9-year-old Greek children who attended primary school during 1997-2007. The study sample consisted of 5125 children matched with their mothers, randomly selected according to region and place of residence, and equally distributed (approximately 500 per year) throughout the study period (1997-2007). A standardised questionnaire was applied; telephone interviews were carried out to collect maternal age, BMI status at the beginning and the end of pregnancy and GWG, birth weight of offspring and BMI status at the ages of 2 and 8 years, as well as several other pregnancy characteristics (e.g. pregnancy duration, gestational medical problems, maternal smoking and alcohol consumption habits, and lactation of offspring after pregnancy). RESULTS: Gestational weight gain was positively associated with the weight status of offspring at all three life stages studied: newborn (birth weight), infant (BMI) and child (BMI) [b = 0.008 (0.001), b = 0.053 (0.009) and b = 0.034 (0.007), respectively, all P < 0.001], after adjusting for maternal age at pregnancy (significant inverse predictor only at age 2 years). The same applied to excessive GWG, as defined by the Institute of Medicine guidelines. CONCLUSIONS: Excessive GWG was associated with a higher risk of greater infant size at birth and a higher BMI status at the ages of 2 and 8 years. Healthcare providers should encourage women to limit their GWG to the range indicated by the current guidelines.


Asunto(s)
Obesidad/epidemiología , Efectos Tardíos de la Exposición Prenatal , Aumento de Peso , Adolescente , Adulto , Peso al Nacer , Índice de Masa Corporal , Niño , Preescolar , Ejercicio Físico , Femenino , Grecia/epidemiología , Encuestas Epidemiológicas , Humanos , Lactante , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Embarazo , Factores de Riesgo , Factores Socioeconómicos , Adulto Joven
8.
BJOG ; 122(13): 1740-7, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25516497

RESUMEN

OBJECTIVE: Smoking and pre-eclampsia (PE) are associated with increases in preterm birth, placental abruption and low birthweight. We evaluated the relationship between prenatal vitamin C and E (C/E) supplementation and perinatal outcomes by maternal self-reported smoking status focusing on outcomes known to be impacted by maternal smoking. DESIGN/SETTING/POPULATION: A secondary analysis of a multi-centre trial of vitamin C/E supplementation starting at 9-16 weeks in low-risk nulliparous women with singleton gestations. METHODS: We examined the effect of vitamin C/E by smoking status at randomisation using the Breslow-Day test for interaction. MAIN OUTCOME MEASURES: The trial's primary outcomes were PE and a composite outcome of pregnancy-associated hypertension (PAH) with serious adverse outcomes. Perinatal outcomes included preterm birth and abruption. RESULTS: There were no differences in baseline characteristics within subgroups (smokers versus nonsmokers) by vitamin supplementation status. The effect of prenatal vitamin C/E on the risk of PE (P = 0.66) or PAH composite outcome (P = 0.86) did not differ by smoking status. Vitamin C/E was protective for placental abruption in smokers (relative risk [RR] 0.09; 95% CI 0.00-0.87], but not in nonsmokers (RR 0.92; 95% CI 0.52-1.62) (P = 0.01), and for preterm birth in smokers (RR 0.76; 95% CI 0.58-0.99) but not in nonsmokers (RR 1.03; 95% CI 0.90-1.17) (P = 0.046). CONCLUSION: In this cohort of women, smoking was not associated with a reduction in PE or the composite outcome of PAH. Vitamin C/E supplementation appears to be associated with a reduction in placental abruption and preterm birth among smokers.


Asunto(s)
Desprendimiento Prematuro de la Placenta/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Preeclampsia/epidemiología , Nacimiento Prematuro/epidemiología , Fumar/epidemiología , Vitaminas/administración & dosificación , Adolescente , Adulto , Ácido Ascórbico/administración & dosificación , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Embarazo , Vitamina E/administración & dosificación , Adulto Joven
9.
BJOG ; 122(10): 1387-94, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25600430

RESUMEN

OBJECTIVE: To determine whether ß2 -adrenoceptor (ß2 AR) genotype is associated with shortening of the cervix or with preterm birth (PTB) risk among women with a short cervix in the second trimester. DESIGN: A case-control ancillary study to a multicentre randomised controlled trial. SETTING: Fourteen participating centres of the Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. POPULATION: Four hundred thirty-nine women, including 315 with short cervix and 124 with normal cervical length. METHODS: Nulliparous women with cervical length <30 mm upon a 16-22-week transvaginal sonogram and controls frequency-matched for race/ethnicity with cervical lengths ≥40 mm were studied. ß2 AR genotype was determined at positions encoding for amino acid residues 16 and 27. MAIN OUTCOME MEASURES: Genotype distributions were compared between case and control groups. Within the short cervix group, pregnancy outcomes were compared by genotype, with a primary outcome of PTB <37 weeks. RESULTS: Genotype data were available at position 16 for 433 women and at position 27 for 437. Using a recessive model testing for association between short cervix and genotype, and adjusted for ethnicity, there was no statistical difference between cases and controls for Arg16 homozygosity (OR 0.7, 95% CI 0.4-1.3) or Gln27 homozygosity (OR 0.9, 95% CI 0.3-2.7). Among cases, Arg16 homozygosity was not associated with protection from PTB or spontaneous PTB. Gln27 homozygosity was not associated with PTB risk, although sample size was limited. CONCLUSIONS: ß2 AR genotype does not seem to be associated with short cervical length or with PTB following the second-trimester identification of a short cervix. Influences on PTB associated with ß2 AR genotype do not appear to involve a short cervix pathway.


Asunto(s)
Genotipo , Nacimiento Prematuro/etiología , Receptores Adrenérgicos beta 2/genética , Incompetencia del Cuello del Útero/genética , Adulto , Estudios de Casos y Controles , Medición de Longitud Cervical , Femenino , Marcadores Genéticos , Homocigoto , Humanos , Polimorfismo de Nucleótido Simple , Embarazo , Segundo Trimestre del Embarazo , Estudios Prospectivos , Incompetencia del Cuello del Útero/diagnóstico por imagen
10.
Am J Perinatol ; 31(8): 655-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24338124

RESUMEN

Venous thromboembolic disease accounts for 9% of all maternal deaths in the United States. In patients at risk for thrombosis, common practice is to start prophylactic doses of low-molecular-weight heparin and transition to unfractionated heparin during the third trimester, with the perception that administration of neuraxial anesthesia will be safer while on unfractionated heparin, as spinal/epidural hematomas have been associated with recent use of low-molecular-weight heparin. In patients receiving prophylactic doses of unfractionated heparin, neuraxial anesthesia may be placed, provided the dose used is 5,000 units twice a day. The American Society of Regional Anesthesia and Pain Medicine guidelines recognize that the safety of neuraxial anesthesia in patients receiving more than 10,000 units per day or more than 2 doses per day is unknown, limiting the theoretical benefit of unfractionated heparin at doses higher than 5,000 units twice a day.


Asunto(s)
Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina/uso terapéutico , Complicaciones Hematológicas del Embarazo/prevención & control , Tromboembolia Venosa/prevención & control , Anestesia Obstétrica/efectos adversos , Sustitución de Medicamentos , Femenino , Hematoma Espinal Epidural/etiología , Hematoma Espinal Epidural/prevención & control , Humanos , Embarazo , Tercer Trimestre del Embarazo
13.
BJOG ; 120(10): 1183-91, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23331974

RESUMEN

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.


Asunto(s)
Antígenos CD/sangre , Preeclampsia/sangre , Proteínas Gestacionales/sangre , Primer Trimestre del Embarazo/sangre , Segundo Trimestre del Embarazo/sangre , Receptores de Superficie Celular/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , Diagnóstico Precoz , Endoglina , Femenino , Humanos , Estudios Longitudinales , Paridad , Factor de Crecimiento Placentario , Preeclampsia/diagnóstico , Preeclampsia/etnología , Embarazo , Factores de Riesgo , Adulto Joven
14.
Vet Immunol Immunopathol ; 229: 110114, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32905850

RESUMEN

Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is one of the main component of the porcine respiratory disease complex (PRDC), which strongly impact the pig production. Although PRRSV is often considered as a primary infection that eases subsequent respiratory coinfections, the possibility that other PRDC components may facilitate PRRSV infection has been largely overlooked. The main cellular targets of PRRSV are respiratory macrophages among them alveolar macrophages (AM) and pulmonary intravascular macrophages (PIM). AM, contrarily to PIM, are directly exposed to the external respiratory environment, among them co-infectious agents. In order to explore the possibility of a co-infections impact on the capacity of respiratory macrophages to replicate PRRSV, we proceed to in vitro infection of AM and PIM sampled from animals presenting different sanitary status, and tested the presence in the respiratory tract of these animals of the most common porcine respiratory pathogens (PCV2, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Mycoplasma hyorhinis, Mycoplasma floculare, Pasteurella multocida, Bordetella bronchiseptica, Streptoccocus suis). In this exploratory study with a limited number of animals, no statistic differences were observed between AM and PIM susceptibility to in vitro PRRSV infection, nor between AM coming from animals presenting very contrasting respiratory coinfection loads.


Asunto(s)
Coinfección/veterinaria , Macrófagos Alveolares/virología , Macrófagos/virología , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino , Infecciones del Sistema Respiratorio/veterinaria , Enfermedades de los Porcinos/virología , Animales , Coinfección/microbiología , Coinfección/virología , Susceptibilidad a Enfermedades/veterinaria , Susceptibilidad a Enfermedades/virología , Femenino , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/microbiología
15.
East Mediterr Health J ; 14(6): 1280-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-19161103

RESUMEN

We report the results of the 2005 Global Youth Tobacco Survey in Lebanon which investigated the self-reported attitudes and behaviours related to tobacco among 3314 Lebanese schoolchildren aged 13-15 years. Current use of any tobacco product was 60.1%; the use of cigarettes was 10% and other tobacco products 59% with male predominance in all areas. About 80% of students lived in homes where others smoked. About 60% of current smokers wanted to quit smoking and 51% of all students had learned about the effects of tobacco in class. Over a quarter (27%) thought that boys who smoke have more friends and 17% believed that smoking makes boys more attractive. The majority of students had been exposed to both anti-smoking media messages and pro-smoking advertisements.


Asunto(s)
Actitud Frente a la Salud , Fumar/epidemiología , Fumar/psicología , Estudiantes , Adolescente , Conducta del Adolescente/psicología , Publicidad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas , Humanos , Líbano/epidemiología , Masculino , Medios de Comunicación de Masas , Motivación , Vigilancia de la Población , Prevalencia , Psicología del Adolescente , Distribución por Sexo , Factores Sexuales , Fumar/efectos adversos , Cese del Hábito de Fumar/psicología , Prevención del Hábito de Fumar , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Encuestas y Cuestionarios , Industria del Tabaco
16.
Placenta ; 36(9): 969-73, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26004735

RESUMEN

BACKGROUND: Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). METHODS: We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. RESULTS: The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. CONCLUSION: Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction.


Asunto(s)
Rotura Prematura de Membranas Fetales/etiología , Placenta/metabolismo , Nacimiento Prematuro/etiología , Estudios Epidemiológicos , Femenino , Rotura Prematura de Membranas Fetales/metabolismo , Humanos , Embarazo , Nacimiento Prematuro/metabolismo
17.
Endocrinology ; 124(4): 1744-53, 1989 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2538310

RESUMEN

We have investigated the interaction of estrogen with GnRH on the regulation of LH subunit mRNA in female hypogonadal (hpg) mice receiving constant frequency and amplitude pulsatile GnRH treatment for up to 18 days. The level of cytosolic common alpha mRNA in female hpg mouse pituitaries was 45 +/- 6% of normal female littermate values, and treatment with pulsatile GnRH increased alpha mRNA to 40% above the normal value at 24 h and 2-4 times normal at 7 and 12 days (P less than 0.001); by 18 days levels had returned to those of untreated hpg controls. Concurrent treatment with estradiol (E2) did not affect those changes. However, in ovariectomized hpg mice the 2- to 4-fold rise in alpha mRNA was sustained for 18 days with GnRH treatment. E2 treatment alone for 7 and 12 days doubled alpha mRNA. LH beta mRNA levels in untreated female hpg mice were between 5-10% of normal values. Levels increased significantly (77 +/- 6.4%) 24 h after GnRH treatment and were normal at 7, 12, and 18 days. E2 together with GnRH did not affect the LH beta mRNA increase at 12 days, but reduced it to 45% of normal at 18 days. Ovariectomy did not alter the LH beta mRNA response to GnRH treatment, and E2 treatment alone did not increase LH beta mRNA. Serum LH concentrations were normalized by GnRH treatment at all times and did not increase in ovariectomized animals. LH release was prevented when E2 was combined with GnRH. Pituitary LH content in hpg mice was 20% of normal and increased gradually with GnRH treatment. Neither concurrent treatment with E2 nor ovariectomy affected the GnRH-induced synthesis of LH. PRL mRNA levels were 30-40% of normal littermate values in untreated female hpg mice, and pulsatile GnRH increased these to 70-80% of normal. E2 alone raised PRL mRNA slightly above normal values, although together with GnRH this rise was attenuated by about 40%. Pulsatile GnRH treatment of ovariectomized hpg mice did not increase PRL mRNA. E2 increased pituitary PRL content, and GnRH did not attenuate this aspect of E2 action. Serum PRL levels rose with E2 treatment at 7 and 12 days, and concurrent GnRH treatment prevented the rise at 12 days. We conclude the following: 1) The stimulatory action of pulsatile GnRH on the expression of both common alpha and LH beta mRNA is rapid (less than 24 h).(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Estradiol/metabolismo , Hipogonadismo/genética , Hormona Luteinizante/genética , Hormonas Liberadoras de Hormona Hipofisaria/metabolismo , Prolactina/genética , Animales , Relación Dosis-Respuesta a Droga , Estradiol/farmacología , Femenino , Regulación de la Expresión Génica , Hipogonadismo/metabolismo , Hormona Luteinizante/análisis , Hormona Luteinizante/sangre , Ratones , Ratones Mutantes , Ovariectomía , Hipófisis/análisis , Hipófisis/fisiopatología , Hipófisis/ultraestructura , Hormonas Liberadoras de Hormona Hipofisaria/farmacología , Prolactina/análisis , Prolactina/sangre , ARN Mensajero/genética , Receptores LHRH/análisis , Factores de Tiempo
18.
Curr Pharm Des ; 9(5): 359-80, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12570814

RESUMEN

Nitric oxide (NO) is a major paracrine mediator and important regulatory agent in various female reproductive processes, such as ovulation, implantation, pregnancy maintenance, labor and delivery. Ovulation: Circulating NO-products are increased during follicle development and decreased right after ovulation. INOS-inhibition results in a 50% reduction of ovulation, an effect completely reversed by an NO. Endometrium/Implantation: NO also regulates endometrial functions such as endometrial receptivity, implantation and menstruation. NO-donors may be useful for promoting fertility, while NO-inhibitors might be used for contraception. Uterine contractility: Throughout gestation myometrial NO-production is upregulated thus contributing to achieve uterine quiescence. Close to term, NO-production decreases promoting effective contractions resulting in labor. Clinical trials have demonstrated that NO-donors are effective tocolytics. Cervical ripening: In contrast to the myometrium, NO-production in the cervix is low during gestation and becomes upregulated once pregnancy advances to term. NO-donors are effective and safe cervical ripening agents. This finding from animal studies has been confirmed by several clinical trials. Vasoreactivity: In blood vessels, NO is a potent vasodilator and platelet-aggregation-inhibitor. Lack of NO during gestation was related to the development of pregnancy-induced hypertension and preeclampsia. In conclusion, NO-donors and NOS-inhibitors may provide novel, effective, safe, and inexpensive drugs to regulate and steer various functions in female reproductive life. The benefits reach from contraception to preventing possibly lethal pregnancy complications such as preeclampsia. Introducing NO-donors as tocolytics and cervical ripening agents may contribute to a reduction of fetal and maternal perinatal morbidity and mortality.


Asunto(s)
Óxido Nítrico/fisiología , Ovulación/metabolismo , Parto/metabolismo , Embarazo/fisiología , Animales , Femenino , Humanos , Óxido Nítrico Sintasa/fisiología , Ovulación/fisiología , Parto/fisiología , Preeclampsia/tratamiento farmacológico , Preeclampsia/enzimología , Preeclampsia/metabolismo , Reproducción/fisiología
19.
J Mol Endocrinol ; 2(3): 213-24, 1989 May.
Artículo en Inglés | MEDLINE | ID: mdl-2751830

RESUMEN

The effect of castration and gonadal steroid replacement on the concentrations of LH-beta and alpha subunit and prolactin mRNA was examined in mice. Mouse LH-beta, alpha and prolactin mRNAs were approximately 0.8, 0.7 and 1.1 kb in size respectively. After ovariectomy, LH-beta mRNA levels increased 2- to 2.5-fold, while alpha mRNA levels increased 2.5-fold 6 and 10 days after ovariectomy. Serum LH rose after 2 days to reach six times control values at 10 days. Pituitary LH content doubled by 8 days after ovariectomy. Prolactin mRNA levels decreased to 50-60% of control at 3, 6, 8 and 10 days after ovariectomy and parallelled the fall in serum prolactin. Pituitary prolactin content fell more slowly, to 50% of intact control values by 10 days. The increase in both LH-beta and alpha subunit mRNA, and decrease in prolactin mRNA, and serum and pituitary hormone changes, after ovariectomy were prevented by oestradiol or oestradiol plus progesterone replacement. Levels of LH-beta mRNA increased more quickly in male than in female mice, the earliest change being seen 24 h after orchidectomy. Maximum values (two- to threefold) were found on day 6 after orchidectomy. Concentrations of alpha mRNA increased by 12 h to between 2 and 2.5 times control from 3 to 10 days after orchidectomy. Serum LH doubled by 12 h and was three to five times greater than control values up to 10 days. Pituitary LH content fell by 48 h before gradually increasing to intact values after 10 days. Prolactin mRNA levels decreased progressively from 2 days after orchidectomy, and this decrease was preceded by a fall in serum and pituitary prolactin which remained low throughout the experiment. Testosterone treatment attenuated the rise in alpha mRNA, prevented the rise in LH-beta mRNA and serum LH and partially restored the decrease in prolactin mRNA seen after orchidectomy. We conclude that in mice, as in rats and ewes, both LH-beta and alpha subunit mRNAs are negatively regulated by gonadal steroids, whereas prolactin mRNA is positively regulated, although there are temporal differences in patterns of mRNA responses between males and females. By comparison with female rats the rise in LH-beta mRNA after ovariectomy was slower in mice. Moreover, the discordant changes in pituitary LH content and LH subunit mRNAs seen in mice after castration were not observed in rats. Furthermore, pituitary prolactin and prolactin mRNA do not fall after orchidectomy of rats.(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Estradiol/farmacología , Hormonas Esteroides Gonadales/farmacología , Hormona Luteinizante/biosíntesis , Progesterona/farmacología , Prolactina/biosíntesis , Animales , Sinergismo Farmacológico , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Hormona Luteinizante/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Orquiectomía , Ovariectomía , Adenohipófisis/análisis , Prolactina/genética , ARN Mensajero/biosíntesis , Testosterona/farmacología
20.
J Mol Endocrinol ; 4(2): 159-67, 1990 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2111706

RESUMEN

There are significant differences between rats and mice in the gonadal regulation of several aspects of gonadotroph function. To investigate whether these extend to the pretranslational regulation of FSH synthesis by gonadal steroids, we have measured FSH-beta mRNA levels following gonadectomy and sex-steroid replacement and have related these to serum and pituitary FSH as a reflection of overall hormone synthesis. In ovariectomized rats, FSH-beta mRNA levels increased by 8 h, decreased, and then rose progressively over the next 28 days. A similar pattern of response was observed in orchidectomized rats. In mice, there were progressive increases in FSH-beta mRNA levels in both males and females following gonadectomy, without evidence of the early peaks observed in rats. In both species, the change in FSH-beta mRNA levels after gonadectomy was greater in females than in males. These changes in FSH-beta mRNA following gonadectomy were paralleled by changes in the serum FSH concentration. In ovariectomized female rats and mice, pituitary FSH stores increased by 8 h and 3 days respectively, whereas in male rats, pituitary FSH content did not rise until 10 days after orchidectomy. The most striking species difference was the marked and prolonged reduction of pituitary FSH after orchidectomy of mice. Treatment of rats and mice from the time of ovariectomy, with a dose of oestradiol that prevents increases in serum LH, only partially attenuated the rises in FSH-beta mRNA and serum FSH and did not prevent the increase in pituitary FSH content. Treatment of intact or orchidectomized rats with testosterone suppressed FSH-beta mRNA levels to 50% below intact control values without affecting pituitary FSH content.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Estradiol/farmacología , Hormona Folículo Estimulante/biosíntesis , Progesterona/farmacología , ARN Mensajero/metabolismo , Testosterona/farmacología , Animales , Femenino , Hormona Folículo Estimulante/análisis , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/genética , Hormona Folículo Estimulante de Subunidad beta , Masculino , Ratones , Ratones Endogámicos BALB C , Orquiectomía , Ovariectomía , Hipófisis/análisis , Ratas , Ratas Endogámicas
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