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1.
Nat Rev Endocrinol ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601352

RESUMO

Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective.

2.
Early Hum Dev ; 147: 105058, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32531744

RESUMO

BACKGROUND: Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. AIM: The aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. STUDY DESIGN: Women were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. SUBJECTS: Nulliparous women with singleton pregnancies. OUTCOME MEASURES: SGA (<10th customised birthweight centile). RESULTS: 5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67-01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (ß 2.56 (95% CI: 0.87-4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. CONCLUSIONS: In this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.

3.
Nat Commun ; 11(1): 2411, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415092

RESUMO

Placental insufficiency can cause fetal growth restriction and stillbirth. There are no reliable screening tests for placental insufficiency, especially near-term gestation when the risk of stillbirth rises. Here we show a strong association between low circulating plasma serine peptidase inhibitor Kunitz type-1 (SPINT1) concentrations at 36 weeks' gestation and low birthweight, an indicator of placental insufficiency. We generate a 4-tier risk model based on SPINT1 concentrations, where the highest risk tier has approximately a 2-5 fold risk of birthing neonates with birthweights under the 3rd, 5th, 10th and 20th centiles, whereas the lowest risk tier has a 0-0.3 fold risk. Low SPINT1 is associated with antenatal ultrasound and neonatal anthropomorphic indicators of placental insufficiency. We validate the association between low circulating SPINT1 and placental insufficiency in two other cohorts. Low circulating SPINT1 is a marker of placental insufficiency and may identify pregnancies with an elevated risk of stillbirth.

4.
Acta Obstet Gynecol Scand ; 99(8): 994-1002, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32017014

RESUMO

INTRODUCTION: Preeclampsia affects about 3% of singleton pregnancies and is characterized by placental dysfunction. It is associated with significant maternal and perinatal morbidity and mortality. The diagnosis of preeclampsia remains a challenge, and the clinical course can develop for weeks before a diagnosis is confirmed. National guidelines have approved placental growth factor (PlGF) testing to rule out suspected preeclampsia, but the utility of repeated PlGF measurement is unknown. The aim of this case series analysis was to evaluate the test performance of repeated PlGF sampling in women presenting with suspected preeclampsia, and to describe relevant clinical outcomes. MATERIAL AND METHODS: Women who presented to maternity services with suspected preeclampsia between 20+0 and 36+6  weeks' gestation who underwent repeat PlGF sampling with a minimum test interval of 7 days were assessed. The outcomes were delivery for preeclampsia within 14 days of sampling, the proportion changing PlGF categories, and time to delivery. RESULTS: In total, 289 women with suspected preeclampsia undergoing repeat PlGF sampling were included. PlGF <100 pg/mL had a high sensitivity (87.5%, 95% confidence interval [CI] 67.6%-97.3%) and a negative predictive value (97.7%, 95% CI 93.5%-99.5%) at the initial test (receiver operating characteristic [ROC] area 0.79, 95% CI 0.68-0.89). Similar test performance was seen for PlGF <100 pg/mL when undertaken as a repeat test (sensitivity 90.7%, 95% CI 85.2%-95.9%, negative predictive value 92.2%, 95% CI 85.3-96.6%). Overall, 25.6% of women changed PlGF category between the first and second PlGF tests. For each PlGF category, determination of time to delivery was similar for first and second tests. CONCLUSIONS: Repeat PlGF measurement demonstrates high negative predictive value for determining preeclampsia requiring delivery in 14 days. Repeat testing may be clinically useful to risk stratify women with ongoing symptoms of disease. Confirmation of the impact of these findings is required in further studies.

5.
Sci Rep ; 9(1): 14114, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575970

RESUMO

Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p < 0.05), suggesting reduced ß- oxidation. DM did not affect placental protein expression or fatty acid profile. Triglyceride levels of placentas from mothers with pre-existing DM were similar to controls, but higher in obese women with gestational DM. Maternal hyperglycemia may not affect placental fatty acid uptake and transport. However, placental ß-oxidation is affected by high glucose and reduced in a subset of women with DM. Abnormal placental lipid metabolism could contribute to increased maternal-fetal lipid transfer and excess fetal growth in some DM pregnancies.

6.
Pregnancy Hypertens ; 17: 12-14, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31487627

RESUMO

Estimates of adherence to antihypertensive treatment in pregnancy are limited; identifying non-adherence could facilitate intervention and optimise blood pressure control. This study aimed to evaluate adherence to antihypertensive treatment amongst pregnant women with chronic hypertension using high-performance liquid chromatography-tandem mass spectrometry instrumentation. Spot urine samples collected from women who were randomised to labetalol or nifedipine were assessed. Samples from 74 women were included; documented prescribing and urine metabolite detection were concordant in 88% (n = 65). Evidence of self-administration of alternative treatment was observed in 8% (n = 6). Measurement of urinary antihypertensive metabolites in pregnancy provides insight into treatment adherence.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adesão à Medicação , Pré-Eclâmpsia/prevenção & controle , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Cuidado Pré-Natal , Adulto , Anti-Hipertensivos/administração & dosagem , Determinação da Pressão Arterial , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Feminino , Humanos , Hipertensão/urina , Labetalol/administração & dosagem , Labetalol/uso terapêutico , Nifedipino/administração & dosagem , Nifedipino/uso terapêutico , Gravidez , Resultado do Tratamento
7.
Nutrients ; 11(2)2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791590

RESUMO

Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004⁻2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks' gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester (139 µg/L, 95% confidence intervals (CI): 126, 158) and London (130 µg/L, 95% CI: 114, 177) and lowest in Leeds (116 µg/L, 95% CI: 99, 135), but the proportion with UIC <50 µg/L was <20% in all three cities. No evidence of an association was observed between UIC and birth weight centile (-0.2% per 50 µg/L increase in UIC, 95% CI: -1.3, 0.8), nor with odds of spontaneous preterm birth (odds ratio = 1.00, 95% CI: 0.84, 1.20). Given the finding of iodine concentrations being insufficient according to World Health Organization (WHO) guidelines amongst pregnant women across all three cities, further studies may be needed to explore implications for maternal thyroid function and longer-term child health outcomes.


Assuntos
Iodo/deficiência , Estado Nutricional , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal , Adulto , Peso ao Nascer , Cidades , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Iodo/urina , Avaliação Nutricional , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/urina , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Diagnóstico Pré-Natal/métodos , Reino Unido/epidemiologia
8.
PLoS Med ; 15(12): e1002710, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30513077

RESUMO

BACKGROUND: Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated. METHODS AND FINDINGS: Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks' gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ≥80 cm, along with any 2 of the following: raised trigycerides (≥1.70 mmol/l [≥150 mg/dl]), reduced high-density lipoprotein cholesterol (<1.29 mmol/l [<50 mg/dl]), raised blood pressure (BP) (i.e., systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg), or raised plasma glucose (≥5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age [LGA], small for gestational age [SGA], and spontaneous preterm birth [sPTB]) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status. CONCLUSIONS: We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently.


Assuntos
Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Paridade/fisiologia , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Austrália/epidemiologia , Estudos de Coortes , Feminino , Humanos , Internacionalidade , Irlanda/epidemiologia , Síndrome Metabólica/sangue , Nova Zelândia/epidemiologia , Gravidez , Complicações na Gravidez/sangue , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia
9.
PLoS One ; 13(11): e0206533, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30395584

RESUMO

OBJECTIVE: To assess the value of in utero placental assessment in predicting adverse pregnancy outcome after reported reduced fetal movements (RFM). METHOD: A non-interventional prospective cohort study of women (N = 300) with subjective RFM at ≥28 weeks' gestation in singleton non-anomalous pregnancies at a UK tertiary maternity hospital. Clinical, sonographic (fetal weight, placental size and maternal, fetal and placental arterial Doppler) and biochemical (maternal serum hCG, hPL, progesterone, PlGF and sFlt-1) assessment was conducted. Multiple logistic regression identified combinations of measurements (models) most predictive of adverse pregnancy outcome (perinatal mortality, birth weight <10th centile, five minute Apgar score <7, umbilical arterial pH <7.1 or base excess <-10, neonatal intensive care admission). Models were compared by test performance characteristics (ROC curve, sensitivity, specificity, positive/negative predictive value, positive/negative likelihood ratios) against baseline care (estimated fetal weight centile, amniotic fluid index and gestation at presentation). RESULTS: 61 (20.6%) pregnancies ended in adverse outcome. Models incorporating PlGF/sFlt-1 ratio and umbilical artery free loop Doppler impedance demonstrated modest improvement in ROC area for adverse outcome (baseline care 0.69 vs. proposed models 0.73-0.76, p<0.05). However, there was little improvement in other test characteristics (baseline vs. best proposed model: sensitivity 21.7% [95% confidence interval 13.1-33.6] vs. 35.8%% [24.4-49.3], specificity 96.6% [93.4-98.3] vs. 94.7% [90.7-97.0], PPV 61.9% [40.9-79.3] vs. 63.3% [45.5-78.1], NPV 82.8% [77.9-86.8] vs. 85.2% [80.0-89.2], positive LR 6.3 [2.8-14.6] vs. 6.7 [3.4-3.3], negative LR 0.81 [0.71-0.93] vs. 0.68 [0.55-0.83]) and wide confidence intervals. Negative post-test probability remained high (16.7% vs. 14.0%). CONCLUSION: Antenatal placental assessment may improve identification of RFM pregnancies at highest risk of adverse pregnancy outcome but further work is required to understand and refine currently available outcome definitions and diagnostic techniques to improve clinical utility.


Assuntos
Movimento Fetal/fisiologia , Placenta/diagnóstico por imagem , Resultado da Gravidez , Adulto , Índice de Apgar , Estudos de Coortes , Cordocentese , Feminino , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido de Baixo Peso , Recém-Nascido , Terapia Intensiva Neonatal , Modelos Logísticos , Estudos Longitudinais , Modelos Biológicos , Morte Perinatal , Placenta/irrigação sanguínea , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Natimorto , Ultrassonografia Pré-Natal
11.
Nitric Oxide ; 80: 37-44, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30099096

RESUMO

Chronic hypertension in pregnancy is associated with significant adverse pregnancy outcomes, increasing the risk of pre-eclampsia, fetal growth restriction and preterm birth. Dietary nitrate, abundant in green leafy vegetables and beetroot, is reduced in vivo to nitrite and subsequently nitric oxide, and has been demonstrated to lower blood pressure, improve vascular compliance and enhance blood flow in non-pregnant humans and animals. The primary aims of this study were to determine the acceptability and efficacy of dietary nitrate supplementation, in the form of beetroot juice, to lower blood pressure in hypertensive pregnant women. In this double-blind, placebo-controlled feasibility trial, 40 pregnant women received either daily nitrate supplementation (70 mL beetroot juice, n = 20) or placebo (70 mL nitrate-depleted beetroot juice, n = 20) for 8 days. Blood pressure, cardiovascular function and uteroplacental blood flow was assessed at baseline and following acute (3 h) and prolonged (8 days) supplementation. Plasma and salivary samples were collected for analysis of nitrate and nitrite concentrations and acceptability of this dietary intervention was assessed based on questionnaire feedback. Dietary nitrate significantly increased plasma and salivary nitrate/nitrite concentrations compared with placebo juice (p < 0.001), with marked variation between women. Compared with placebo, there was no overall reduction in blood pressure in the nitrate-treated group; however there was a highly significant correlation between changes in plasma nitrite concentrations and changes in diastolic blood pressure in the nitrate-treated arm only (r = -0.6481; p = 0.0042). Beetroot juice supplementation was an acceptable dietary intervention to 97% of women. This trial confirms acceptability and potential efficacy of dietary nitrate supplementation in pregnant women. Conversion of nitrate to nitrite critically involves oral bacterial nitrate reductase activities. We speculate that differences in efficacy of nitrate supplementation relate to differences in the oral microbiome, which will be investigated in future studies.


Assuntos
Beta vulgaris , Pressão Sanguínea/efeitos dos fármacos , Sucos de Frutas e Vegetais , Hipertensão Induzida pela Gravidez/dietoterapia , Nitratos/administração & dosagem , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido , Nitratos/sangue , Placebos , Gravidez , Resultado do Tratamento
12.
Artigo em Inglês | MEDLINE | ID: mdl-29753307

RESUMO

INTRODUCTION: Large-for-gestational-age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in large-for-gestational-age infants. MATERIAL AND METHODS: Nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between large-for-gestational-age infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to a neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a priori hypotheses of association and included maternal demography, anthropometric measures and self-reported physical activity (15 and 20 weeks), fetal biometry (20 weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity. RESULTS: Among term pregnancies, prevalence of large-for-gestational-age infants was 9.3% (491/5255), with 11.8% (58/491) prevalence of neonatal morbidity. Random glucose at 20 weeks (odds ratio 1.52; 95% confidence interval 1.17-1.97, per 1 mmol/L increase) and no regular physical activity at 20 weeks (odds ratio 3.93; 95% confidence interval 1.75-8.83) were associated with increased risk of neonatal morbidity after adjustment for birthweight, gestational age at delivery and gestational diabetes. The increased risk associated with higher glucose levels was not evident in women with regular physical activity or without obesity. CONCLUSIONS: Regular physical activity in mid-pregnancy is associated with lower risk for neonatal morbidity in large-for-gestational-age infants and seems to offer protection against the increased risk associated with higher maternal glucose levels.

13.
Am J Physiol Regul Integr Comp Physiol ; 315(1): R36-R47, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29513563

RESUMO

Black ethnicity is associated with worse pregnancy outcomes in women with chronic hypertension. Preexisting endothelial and renal dysfunction and poor placentation may contribute, but pathophysiological mechanisms underpinning increased risk are poorly understood. This cohort study aimed to investigate the relationship between ethnicity, superimposed preeclampsia, and longitudinal changes in markers of endothelial, renal, and placental dysfunction in women with chronic hypertension. Plasma concentrations of placental growth factor (PlGF), syndecan-1, renin, and aldosterone and urinary angiotensinogen-to-creatinine ratio (AGTCR), protein-to-creatinine ratio (PCR), and albumin-to-creatinine ratio (ACR) were quantified during pregnancy and postpartum in women with chronic hypertension. Comparisons of longitudinal biomarker concentrations were made using log-transformation and random effects logistic regression allowing for gestation. Of 117 women, superimposed preeclampsia was diagnosed in 21% ( n = 25), with 24% ( n = 6) having an additional diagnosis of diabetes. The cohort included 63 (54%) women who self-identified as being of black ethnicity. PlGF concentrations were 67% lower [95% confidence interval (CI) -79 to -48%] and AGTCR, PCR, and ACR were higher over gestation, in women with subsequent superimposed preeclampsia (compared with those without superimposed preeclampsia). PlGF <100 pg/ml at 20-23.9 wk of gestation predicted subsequent birth weight <3rd percentile with 88% sensitivity (95% CI 47-100%) and 83% specificity (95% CI 70-92%). Black women had 43% lower renin (95% CI -58 to -23%) and 41% lower aldosterone (95%CI -45 to -15%) concentrations over gestation. Changes in placental (PlGF) and renal (AGTCR/PCR/ACR) biomarkers predated adverse pregnancy outcome. Ethnic variation in the renin-angiotensin-aldosterone system exists in women with chronic hypertension in pregnancy and may be important in treatment selection.


Assuntos
Grupo com Ancestrais do Continente Africano , Endotélio Vascular/metabolismo , Hipertensão Induzida pela Gravidez/etnologia , Hipertensão Induzida pela Gravidez/metabolismo , Rim/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/etnologia , Pré-Eclâmpsia/metabolismo , Adulto , Angiotensinogênio/urina , Biomarcadores/sangue , Biomarcadores/urina , Doença Crônica , Creatinina/urina , Endotélio Vascular/fisiopatologia , Inglaterra/epidemiologia , Feminino , Humanos , Hipertensão Induzida pela Gravidez/fisiopatologia , Rim/fisiopatologia , Estudos Longitudinais , Placenta/fisiopatologia , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Albumina Sérica Humana/urina , Fatores de Tempo
14.
J Obstet Gynaecol Res ; 44(1): 124-133, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29027317

RESUMO

AIM: Underlying mechanisms of poor pregnancy outcome in obese (OB) mothers (body mass index [BMI] ≥ 30 kg/m2 ) are unknown. Our studies demonstrate that OB pregnant women have altered myometrial artery (MA) function related to the thromboxane and nitric oxide pathways. In obesity, increased central fat mass is associated with an altered endocrine milieu. We tested the hypothesis that in OB pregnant women the omentum, a central fat store, releases factors that promote dysfunction in normal MAs. METHODS: Myometrial and omental adipose tissue biopsies were obtained from women with uncomplicated term pregnancies. Omental adipose tissue explants from six normal weight (NW; BMI 18.5-24.9 kg/m2 ) and six OB (BMI ≥ 30 kg/m2 ) women were cultured and the conditioned medium collected and pooled to produce NW medium and OB medium. Adipokine concentrations were measured using enzyme-linked immunosorbent assays. Wire myography was used to assess the effect of conditioned medium (NW or OB; N = 7) or leptin (100 nM; N = 5) exposure on MA responses to U46619 (thromboxane-mimetic) and bradykinin (endothelial-dependent vasodilator). RESULTS: OB medium had higher leptin and lower adiponectin levels than NW medium. U46619 and bradykinin concentration response curves shifted upwards in MAs exposed to OB medium but were unaffected by leptin. CONCLUSIONS: Omental adipose tissue from OB pregnant women produced altered concentrations of adipokines. Acute OB medium exposure induced MA dysfunction, an effect not mirrored by exposure to leptin. These data suggest that an aberrant endocrine environment created by increased central adiposity in OB pregnant women induces vascular endothelial dysregulation, which may predispose them to a poor pregnancy outcome.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Leptina/metabolismo , Miométrio/irrigação sanguínea , Miométrio/metabolismo , Obesidade/metabolismo , Omento/metabolismo , Complicações na Gravidez/metabolismo , Células Cultivadas , Feminino , Humanos , Gravidez , Adulto Jovem
15.
Placenta ; 60: 110-114, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28855067

RESUMO

Several maternal and pregnancy characteristics have been associated with an increased risk of preeclampsia in epidemiological studies. This review discusses metabolic risk factors in particular and their interaction with other maternal and/or pregnancy characteristics. Examples of research studies that have used data from women with specific characteristics or explored the interaction between risk factors are discussed. Suggestions for future research using large data sets and incorporating knowledge of cardiovascular disease and other metabolic diseases are also highlighted.


Assuntos
Pré-Eclâmpsia/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Idade Materna , Obesidade/complicações , Paridade , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Técnicas de Reprodução Assistida/efeitos adversos , Fatores de Risco
16.
Hypertension ; 70(5): 915-922, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28893900

RESUMO

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12+0-27+6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P=0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936.


Assuntos
Pressão Arterial/efeitos dos fármacos , Hipertensão , Labetalol , Nifedipino , Complicações Cardiovasculares na Gravidez , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Determinação da Pressão Arterial/métodos , Monitoramento de Medicamentos/métodos , Feminino , Idade Gestacional , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Labetalol/administração & dosagem , Labetalol/efeitos adversos , Nifedipino/administração & dosagem , Nifedipino/efeitos adversos , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Análise de Onda de Pulso/métodos , Resultado do Tratamento , Reino Unido
17.
Am J Obstet Gynecol ; 217(4): 453.e1-453.e12, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28651860

RESUMO

BACKGROUND: Currently, 2-dimensional ultrasound estimation of fetal size rather than fetal growth is used to define fetal growth restriction, but single estimates in late pregnancy lack sensitivity and may identify small for gestational age rather than growth restriction. Single or longitudinal measures of 3-dimensional fractional thigh volume may address this problem. OBJECTIVE: We sought to derive normal values for 3-dimensional fractional thigh volume in the third trimester, determine if fractional thigh volume is superior to 2-dimensional ultrasound biometry alone for detecting fetal growth restriction, and determine whether individualized growth assessment parameters have the potential to identify fetal growth restriction remote from term delivery. STUDY DESIGN: This was a longitudinal prospective cohort study of 115 unselected pregnancies in a tertiary referral unit (St Mary's Hospital, Manchester, United Kingdom). Standard 2-dimensional ultrasound biometry measurements were obtained, along with fractional thigh volume measurements (based on 50% of the femoral diaphysis length). Measurements were used to calculate estimated fetal weight (Hadlock). Individualized growth assessment parameters and percentage deviations in longitudinally measured biometrics were determined using a Web-based system (iGAP; http://iGAP. RESEARCH: bcm.edu). Small for gestational age was defined <10th and fetal growth restriction <3rd customized birthweight centile. Logistic regression was used to compare estimated fetal weight (Hadlock), estimated fetal weight (biparietal diameter-abdominal circumference-fractional thigh volume), fractional thigh volume, and abdominal circumference for the prediction of small for gestational age or fetal growth restriction at birth. Screening performance was assessed using area under the receiver operating characteristic curve. RESULTS: There was a better correlation between fractional thigh volume and estimated fetal weight ((biparietal diameter-abdominal circumference-fractional thigh volume) obtained at 34-36 weeks with birthweight than between 2-dimensional biometry measures such as abdominal circumference and estimated fetal weight (Hadlock). There was also a modest improvement in the detection of both small for gestational age and fetal growth restriction using fractional thigh volume-derived measures compared to standard 2-dimensional measurements (area under receiver operating characteristic curve, 0.86; 95% confidence interval, 0.79-0.94, and area under receiver operating characteristic curve, 0.92; 95% confidence interval, 0.85-0.99, respectively). CONCLUSION: Fractional thigh volume measurements offer some improvement over 2-dimensional biometry for the detection of late-onset fetal growth restriction at 34-36 weeks.


Assuntos
Diáfises/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Retardo do Crescimento Fetal/diagnóstico , Imageamento Tridimensional , Ultrassonografia Pré-Natal , Estudos de Coortes , Diáfises/crescimento & desenvolvimento , Feminino , Fêmur/crescimento & desenvolvimento , Peso Fetal , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Estudos Longitudinais , Gravidez , Terceiro Trimestre da Gravidez , Circunferência da Cintura
18.
J Ultrasound Med ; 36(7): 1415-1429, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28339117

RESUMO

OBJECTIVES: To assess intraexaminer and interexaminer reliability of 3-dimensional fetal sonographic measurements. METHODS: Three-dimensional fetal organ volumes (head, kidney, total thigh volume, and fractional thigh volume) were acquired during the second and third trimesters, with the addition of placental volume in the second trimester, by 2 different experienced, blinded sonographers. Fifty-eight fetuses were examined from 21 to 39 weeks' gestation. Intraexaminer and Interexaminer reliability was assessed with Bland-Altman plots, and their 95% limits of agreement and intraclass correlation coefficients. RESULTS: The most significant interexaminer error was observed in the second-trimester kidney volume (95% limits of agreement, ± 110%), and the best agreement was for the third-trimester fractional thigh volume (95% limits of agreement, ± 25%) and second-trimester head volume (95% limits of agreement, -7%-25%). Second- and third-trimester intraclass correlation coefficient results were all greater than 0.75, apart from second-trimester kidney volume intraexaminer (0.374) and interexaminer (0.061) measurements, second-trimester placenta interexaminer measurements (0.390), and third-trimester kidney interexaminer measurements (0.647). CONCLUSIONS: Three-dimensional fetal sonographic volumes of the head, kidney, total thigh, and placenta have limited reproducibility, and improvements in measurement techniques are needed before they can be used routinely to assess fetal growth. The 3-dimensional fractional thigh volume can be reliably obtained in the late third trimester.


Assuntos
Peso Fetal/fisiologia , Feto/diagnóstico por imagem , Feto/fisiologia , Imageamento Tridimensional/métodos , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Tamanho do Órgão , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Obesity (Silver Spring) ; 25(2): 460-467, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28008746

RESUMO

OBJECTIVE: To compare early pregnancy clinical and biomarker risk factors for later development of preeclampsia between women with obesity (body mass index, BMI ≥30 kg/m2 ) and those with a normal BMI (20-25 kg/m2 ). METHODS: In 3,940 eligible nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study, a total of 53 biomarkers of glucose and lipid metabolism, placental function, and known markers of preeclampsia were measured at 14 to 16 weeks' gestation. Logistic regression was performed to identify clinical and biomarker risk factors for preeclampsia in women with and without obesity. RESULTS: Among 834 women with obesity and 3,106 with a normal BMI, 77 (9.2%) and 105 (3.4%) developed preeclampsia, respectively. In women with obesity, risk factors included a family history of thrombotic disease, low plasma placental growth factor, and higher uterine artery resistance index at 20 weeks. In women with a normal BMI, a family history of preeclampsia or gestational hypertension, mean arterial blood pressure, plasma endoglin and cystatin C, and uterine artery resistance index were associated with preeclampsia, while high fruit intake was protective. CONCLUSIONS: Women with obesity and a normal BMI have different early pregnancy clinical and biomarker risk factors for preeclampsia.


Assuntos
Obesidade/sangue , Obesidade/complicações , Pré-Eclâmpsia/sangue , Adulto , Biomarcadores/sangue , Feminino , Idade Gestacional , Humanos , Obesidade/fisiopatologia , Paridade , Fator de Crescimento Placentário/sangue , Gravidez , Proteínas da Gravidez , Fatores de Risco , Artéria Uterina/fisiopatologia , Resistência Vascular/fisiologia
20.
Reprod Toxicol ; 62: 77-86, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27142189

RESUMO

Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15±1 and 20±1 weeks' gestation. Cases [278 Preeclampsia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks' gestation was associated with SPTB independent of cigarette smoking status [adj OR 2.28 (95% CI:1.45-3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41-3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks' gestation had a greater effect size [adj OR 5.44 (95% CI 2.44-12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern.


Assuntos
Uso da Maconha/efeitos adversos , Nascimento Prematuro/epidemiologia , Adulto , Austrália/epidemiologia , Feminino , Humanos , Irlanda/epidemiologia , Nova Zelândia/epidemiologia , Razão de Chances , Gravidez , Risco , Reino Unido/epidemiologia , Adulto Jovem
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