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1.
JMIR Hum Factors ; 7(3): e17416, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940610

RESUMO

BACKGROUND: Health information technology (HIT) and associated data analytics offer significant opportunities for tackling some of the more complex challenges currently facing the health care sector. However, to deliver robust health care service improvements, it is essential that HIT solutions be designed by parallelly considering the 3 core pillars of health care quality: clinical effectiveness, patient safety, and patient experience. This requires multidisciplinary teams to design interventions that both adhere to medical protocols and achieve the tripartite goals of effectiveness, safety, and experience. OBJECTIVE: In this paper, we present a design tool called Integrated Patient Journey Mapping (IPJM) that was developed to assist multidisciplinary teams in designing effective HIT solutions to address the 3 core pillars of health care quality. IPJM is intended to support the analysis of requirements as well as to promote empathy and the emergence of shared commitment and understanding among multidisciplinary teams. METHODS: A 6-month, in-depth case study was conducted to derive findings on the use of IPJM during Learning to Evaluate Blood Pressure at Home (LEANBH), a connected health project that developed an HIT solution for the perinatal health context. Data were collected from over 700 hours of participant observations and 10 semistructured interviews. RESULTS: The findings indicate that IPJM offered a constructive tool for multidisciplinary teams to work together in designing an HIT solution, through mapping the physical and emotional journey of patients for both the current service and the proposed connected health service. This allowed team members to consider the goals, tasks, constraints, and actors involved in the delivery of this journey and to capture requirements for the digital touchpoints of the connected health service. CONCLUSIONS: Overall, IPJM facilitates the design and implementation of complex HITs that require multidisciplinary participation.

2.
PLoS Med ; 17(8): e1003182, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810184

RESUMO

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.


Assuntos
Pais , Obesidade Pediátrica/epidemiologia , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , América do Norte/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Nascimento Prematuro/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Fatores de Risco , Fumar/tendências
3.
Artigo em Inglês | MEDLINE | ID: mdl-32617576

RESUMO

CONTEXT: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. OBJECTIVE: To investigate the diagnostic and therapeutic potential of the angiogenesis markers, FKBPL-CD44, in preeclampsia pathogenesis. DESIGN AND INTERVENTION: FKBPL and CD44 plasma or placental concentration was determined in women pre- or post-diagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signalling. SETTINGS AND PARTICIPANTS: Human samples pre-diagnosis (15 and 20 weeks' gestation; n≥57), or post-diagnosis (n=18 for plasma; n=4 for placenta) of preeclampsia were used to determine FKBPL and CD44 concentration, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid. MAIN OUTCOME MEASURES: Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signalling in trophoblast and endothelial cells were assessed. RESULTS: The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks' gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.5-fold increased risk of preeclampsia (OR=2.5, 95% CI 1.12-5.41, p=0.02). In combination with high mean arterial blood pressure (MABP > 82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, p=0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signalling enhancing cell angiogenesis. CONCLUSIONS: The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

4.
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.

5.
PLoS One ; 15(5): e0232664, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401767

RESUMO

OBJECTIVE: To assess the incidence and risk factors for hyperglycemia in pregnancy in a cohort of Brazilian nulliparous pregnant women. MATERIALS AND METHODS: This is a secondary analysis of a multicenter cohort study that enrolled 1,008 nulliparous pregnant women at 19-21 weeks. Exclusion criteria included chronic exposure to corticosteroids and previous diabetes. Bivariate and multivariate analyses by Poisson regression were used to identify associated factors. RESULTS: The incidence of hyperglycemia in pregnancy was 14.9% (150/1,008), and 94.7% of these cases were gestational diabetes mellitus (142/150). Significant associated factors included a family history of diabetes mellitus, maternal overweight or obesity at enrollment, and previous maternal conditions (polycystic ovarian syndrome, thyroid dysfunctions and hypertensive disorders). A BMI ≥ 26.3Kg/m2 (RRadj 1.87 [1.66-2.10]) and a family history of diabetes mellitus (RRadj 1.71 [1.37-2.15]) at enrollment were independent risk factors for HIP. CONCLUSIONS: A family history of diabetes mellitus and overweight or obesity (until 19-21 weeks of gestation) may be used as selective markers for HIP in Brazilian nulliparous women. Given the scarcity of results in nulliparous women, our findings may contribute to determine the optimal diagnostic approach in populations of similar socioeconomic characteristics.


Assuntos
Diabetes Gestacional/epidemiologia , Hiperglicemia/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Brasil/epidemiologia , Feminino , Humanos , Incidência , Sobrepeso/epidemiologia , Gravidez , Fatores de Risco , Adulto Jovem
6.
Matern Child Nutr ; : e13011, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32350987

RESUMO

Maternal obesity is associated with increased risk of gestational diabetes and other complications. Although antenatal interventions to help prevent these complications are ongoing, an understanding of overweight and obese pregnant women's opinions and attitudes is lacking. Therefore, this study aims to explore these women's experiences and perceptions of dietary behaviours and weight management during pregnancy. Secondary analysis of qualitative data originally collected to examine lifestyle behaviours in pregnant women was conducted. The data were from a purposive sample of overweight and obese pregnant women attending a public antenatal clinic in Cork, Ireland. The data were explored using thematic analysis. Interviews with 30 overweight and obese pregnant women were analysed. Three themes were developed relating to overweight and obese women's dietary behaviours and weight management perceptions including 'pregnancy's influence on dietary behaviours', 'external influences on dietary behaviours' and 'perception of and preferences for weight related advice and resources'. Together these themes reveal women's experiences of diet and how pregnancy factors (physiological changes) and external factors (family and friends) can influence dietary behaviours. Furthermore, perceptions of weight management advice and lack thereof were highlighted with women drawing attention to potential resources for future use during pregnancy. This study provides important insights into overweight and obese pregnant women's dietary behaviours and perceptions of weight management. According to these findings, there is a need for clear and unambiguous information about weight management, acceptable weight gain, food safety and how to achieve a balanced diet.

7.
Biol Sex Differ ; 11(1): 25, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370773

RESUMO

BACKGROUND: Asymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way. METHODS: For this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses. RESULTS: Prevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight > 90th percentile (p < 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI < 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p < 0.001), but also lower rates of stillbirth (p = 0.041) and less often Apgar scores < 7 (p = 0.060). CONCLUSIONS: Among SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis. TRIAL REGISTRATION: ACTRN12607000551493.

8.
Acta Psychiatr Scand ; 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32337718

RESUMO

Using a large Swedish-based registry cohort, we estimated that preeclampsia is associated with a 25% increase in the likelihood of autism spectrum disorder (ASD), and a 15% increase in the likelihood of attention deficit hyperactivity disorder (ADHD) (n=2,842,230 and 2,047,619 respectively)(1, 2). Evidence suggests that certain non-communicable diseases may have an effect across several generations(3, 4). However, whether there is any intergenerational link between preeclampsia exposure and ASD or ADHD outcome in the child is unknown. Therefore, we conducted a cross family analysis to examine the intergenerational association between preeclampsia and ASD and ADHD using a large population-based cohort.

9.
PLoS One ; 15(3): e0230977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231385

RESUMO

INTRODUCTION: Pre-eclampsia is a major cause of maternal and fetal mortality and morbidity worldwide. Its pathophysiology remains unclear, but mitochondrial dysfunction and oxidative stress have been implicated. L-Ergothioneine is a naturally occurring, water-soluble betaine, that has demonstrated antioxidant properties. Using the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia, this study aimed to define the plasma metabolic profile following treatment with L-Ergothioneine. METHODS: The effect of L-Ergothioneine (ET) treatment was explored using in vivo treatment in rats: Sham control (SC, n = 5), RUPP control (RC, n = 5), Sham +ET (ST, n = 5), RUPP +ET (RT, n = 5). Differential expression of plasma metabolites were obtained using untargeted liquid chromatography coupled to mass spectrometry. Statistical analysis was performed on normalised data comparing RC to SC, RT to RC, and RT to ST. Metabolites significantly altered (FDR < 0.05) were identified through database search. RESULTS: We report significantly lower levels of L-palmitoylcarnitine in RC compared to SC, a fatty acyl substrate involved in beta-oxidation in the mitochondria. We report that a metabolite that has been associated with oxidative stress (Glutamylcysteine) was detected at significantly higher levels in RT vs RC and RT vs ST. Five metabolites associated with inflammation were significantly lower in RT vs RC and three metabolites in RT vs ST, demonstrating the anti-inflammatory effects of ET in the RUPP rat model of pre-eclampsia. CONCLUSIONS: L-Ergothioneine may help preserve mitochondrial function by increasing antioxidant levels, and reducing inflammatory responses associated with pre-eclampsia. This study shows the potential of L-Ergothioneine as a treatment for pre-eclampsia.


Assuntos
Ergotioneína/farmacologia , Metaboloma/efeitos dos fármacos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Perfusão , Gravidez , Pressão , Ratos , Ratos Sprague-Dawley
10.
Artigo em Inglês | MEDLINE | ID: mdl-32228063

RESUMO

Aims: Although preeclampsia (PE) has been attributed to excessive oxidative stress (OS) in the placenta, mild antioxidants failed to prevent PE in clinical trials. As mitochondria are a major source of OS, this study assessed the potential of a potent mitochondria-targeting antioxidant MitoQ in the prevention of PE. Results: Placentas from women with PE and from reduced uterine perfusion pressure (RUPP) mice demonstrated significantly higher OS, along with increased mitochondrial damage and compromised glutathione peroxidase (GPx) activities. MitoQ administration during late gestation alleviated RUPP-induced PE; whereas early-pregnancy MitoQ treatment not only exacerbated blood pressure, fetal growth restriction, and proteinuria but also reduced the labyrinth/spongiotrophoblast ratio and blood sinuses in the labyrinth. Invasion (Matrigel transwell) and migration (wound healing assay) of trophoblasts were greatly improved by 1 µM hydrogen peroxide (H2O2), but this improvement was abolished by MitoQ or MitoTempo. Mild OS enhanced the expression of miR-29b-3p, which regulates five genes involved in viability and mobility, in HTR8-S/Vneo cells. Innovation and Conclusions: Although the potent mitochondrial-targeting antioxidant MitoQ protects against hypertension and kidney damage induced by RUPP in mice when administered in late gestation, it exacerbates the PE-like phenotype when given in early gestation by interfering with placenta formation because mild OS is required to stimulate trophoblast proliferation, invasion, and migration. Eliminating trophoblastic OS during early pregnancy may lead to compromised placentation and a risk of diseases of placental origin. Therefore, antioxidant therapy for pregnant women should be carefully considered.

11.
Nutr Res Rev ; : 1-28, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32051057

RESUMO

Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

12.
Metabolomics ; 16(2): 19, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31974687

RESUMO

INTRODUCTION: Preterm birth (PTB) is defined as birth occurring before 37 weeks' gestation, affects 5-9% of all pregnancies in developed countries, and is the leading cause of perinatal mortality. Spontaneous preterm birth (sPTB) accounts for 31-50% of all PTB, but the underlying pathophysiology is poorly understood. OBJECTIVE: This study aimed to decipher the lipidomics pathways involved in pathophysiology of sPTB. METHODS: Blood samples were taken from SCreening fOr Pregnancy Endpoints (SCOPE), an international study that recruited 5628 nulliparous women, with a singleton low-risk pregnancy. Our analysis focused on plasma from SCOPE in Cork. Discovery profiling of the samples was undertaken using liquid chromatography-mass spectrometry Lipidomics, and features significantly altered between sPTB (n = 16) and Control (n = 32) groups were identified using empirical Bayes testing, adjusting for multiple comparisons. RESULTS: Twenty-six lipids showed lower levels in plasma of sPTB compared to controls (adjusted p < 0.05), including 20 glycerophospholipids (12 phosphatidylcholines, 7 phosphatidylethanolamines, 1 phosphatidylinositol) and 6 sphingolipids (2 ceramides and 4 sphingomyelines). In addition, a diaglyceride, DG (34:4), was detected in higher levels in sPTB compared to controls. CONCLUSIONS: We report reduced levels of plasma phospholipids in sPTB. Phospholipid integrity is linked to biological membrane stability and inflammation, while storage and breakdown of lipids have previously been implicated in pregnancy complications. The contribution of phospholipids to sPTB as a cause or effect is still unclear; however, our results of differential plasma phospholipid expression represent another step in advancing our understanding of the aetiology of sPTB. Further work is needed to validate these findings in independent pregnancy cohorts.

13.
J Child Psychol Psychiatry ; 61(2): 131-139, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31531876

RESUMO

BACKGROUND: The environmental contribution of autism spectrum disorder (ASD) is approximately 17%-50%, highlighting the importance of investigating factors potentially contributing to the likelihood of its development, and of gaining a greater understanding of the pathogenesis surrounding ASD. The objective of this study was to examine the association between preeclampsia and ASD using a population-based cohort study. METHODS: All singleton live births in Sweden from 1982 to 2010 were included, using data from Swedish National Registers. Exposures of interest included: (a) preeclampsia (classified according to ICD-8, ICD-9 and ICD-10) and (b) preeclampsia and small for gestational age (SGA) combined, used as a proxy for preeclampsia with placental dysfunction. ASD status was based on ICD-9 and ICD-10. The cohort consisted of 2,842,230 children, with 54,071 cases of ASD. Follow-up began from the child's first birthday, and data were censored at first diagnosis of ASD, death, migration or end of study period (31st December 2016). We conducted multivariate Cox proportional hazards regression analysis, adjusting for several perinatal and sociodemographic factors, selected a priori. We further controlled for shared genetic and familial confounding using sibling-matched analysis. RESULTS: In the adjusted Cox proportional hazards regression analysis, preeclampsia was associated with a 25% increase in the likelihood of ASD (Hazard Ratio (HR): 1.25, 95% CI:1.19, 1.30) compared with those unexposed to preeclampsia, while in the sibling-matched analysis the HR was 1.17 (95% CI: 1.06, 1.28). The HR for preeclampsia and SGA combined was 1.66 (95% CI: 1.49, 1.85) in the adjusted Cox model and 1.95 (95% CI: 1.53, 2.48) in the sibling-matched analysis. CONCLUSIONS: Exposure to preeclampsia or preeclampsia/SGA (i.e. SGA baby exposed to preeclampsia) was associated with ASD. The stronger association with preeclampsia/SGA than preeclampsia alone suggests that placental pathology may be a mechanism for the increased likelihood of ASD.

14.
Acta Paediatr ; 109(5): 982-988, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31520432

RESUMO

AIM: Breastfeeding is associated with IQ, school attendance and income. Despite the known benefits of breastfeeding, the rate of exclusive breastfeeding up to 6 months is low globally. We examined the effect of short-term breastfeeding on long-term IQ. METHODS: In this secondary analysis of the prospective Cork BASELINE Birth Cohort Study, children were categorised as predominantly breastfed (n = 288) versus exclusively formula-fed (n = 254) at 2-months of age. Infants (n = 404) receiving mixed feeding were excluded. Outcome was assessed using the KBIT-II at 5 years. Multivariable linear regression was used to adjust for confounding variables. RESULTS: Following adjustment for confounding variables, children, predominately breastfed at 2 months of age, demonstrated increased overall IQ (2.00 points (95% CI: 0.35 to 3.65); P = .018) and non-verbal IQ at 5 years of age (1.88 points (95% CI: 0.22 to 3.54); P = .027) compared with those never breastfed. No significant relationship was found with verbal IQ (P = .154). CONCLUSION: A significant increase in composite and non-verbal IQ at 5 years of age was associated with short-term breastfeeding. This study adds to a growing body of evidence that short-term breastfeeding promotes healthy cognitive development.

15.
Hypertension ; 75(2): 561-568, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31865793

RESUMO

Preeclampsia is a multifactorial hypertensive disorder of pregnancy founded on abnormal placentation, and the resultant placental ischemic microenvironment is thought to play a crucial role in its pathophysiology. Placental ischemia because of fluctuations in the delivery of oxygen results in oxidative stress, and recent evidence suggests that mitochondrial dysfunction may be a prime mediator. However, large clinical trials of therapeutic antioxidants such as vitamins C and E for the treatment of preeclampsia have been disappointing. L-(+)-ergothioneine (ERG)-an unusual amino acid betaine derived from histidine-has important cytoprotective and antioxidant properties under conditions of high oxidative stress. In this study, we investigated the potential therapeutic effects of administration of ERG in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. ERG (25 mg/kg per day) was administered to rats on gestational day 11. On gestational day 14, RUPP surgery was performed, and on gestational day 19, blood pressure (mean arterial pressure) and fetal growth were measured. Production of mitochondria-specific H2O2 was analyzed in vivo in kidney samples. ERG ameliorated the hypertension (129±3 versus 115±4 mm Hg; P=0.01; n=8) and significantly increased pup weight in RUPP rats. ERG also significantly decreased circulating levels of antiangiogenic sFlt-1 (soluble fms-like tyrosine kinase-1) in RUPP rats (1367±245 pg/mL; P=0.04). Mitochondria-specific H2O2 (0.022±0.003 versus 0.029±0.001; MitoP/B ratio, n=3; P=0.05) was also significantly decreased in kidney tissue in RUPP rats treated with ERG. These data support the potential use of ERG for the treatment of preeclampsia.


Assuntos
Ergotioneína/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Prenhez , Fluxo Sanguíneo Regional/efeitos dos fármacos , Útero/irrigação sanguínea , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez , Ratos , Ratos Sprague-Dawley , Útero/fisiopatologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
PLoS Med ; 16(10): e1002977, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31647817

RESUMO

[This corrects the article DOI: 10.1371/journal.pmed.1002875.].

17.
PLoS One ; 14(10): e0223856, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31665164

RESUMO

BACKGROUND: Several studies reported an association between Caesarean section (CS) birth and childhood obesity. However, there are several limitations in the current literature. These include an inability to distinguish between planned and emergency CS, small study sample sizes and not adjusting for pre-pregnancy body-mass-index (BMI). We examined the association between CS delivery and childhood obesity using the United Kingdom Millennium Cohort Study (MCS). METHODS: Mother-infant pairs were recruited into the MCS. Use of sampling weights ensured the sample was representative of the population. The exposure was categorised as normal vaginal delivery (VD) [reference], assisted VD, planned CS and emergency CS. Childhood obesity prevalence, at age three, five, seven, eleven and fourteen years was calculated using the International Obesity Taskforce criteria. Mixed-effects linear regression models were fitted with associations adjusted for several potential confounders like maternal age, pre-pregnancy BMI, education and infant macrosomia. Linear regression models were fitted evaluating body fat percentage (BF%), at age seven and fourteen years. RESULTS: Of the 18,116 infants, 3872 (21.4%) were delivered by CS; 9.2% by planned CS. Obesity prevalence was 5.4%, 5.7%, 6.5%, 7.1% and 7.6% at age three, five, seven, eleven and fourteen years respectively. The mixed-effects linear regression model showed no association between planned (adjusted mean difference = 0.00; [95% confidence interval (CI) -0.10; 0.10], p-value = 0.97) or emergency CS (adjusted mean difference = 0.08; [95% CI -0.01; 0.17], p-value = 0.09) and child BMI. At age seven years, there was no association between planned CS and BF% (adjusted mean difference = 0.13; [95% CI -0.23; 0.49]); there was no association at age fourteen years. CONCLUSIONS: Infants born by planned CS did not have a significantly higher BMI or BF% compared to those born by normal VD. This may suggest that the association, described in the literature, could be due to the indications/reasons for CS birth or residual confounding.


Assuntos
Cesárea/estatística & dados numéricos , Obesidade Pediátrica/epidemiologia , Tecido Adiposo/metabolismo , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Obesidade Pediátrica/patologia , Fatores de Risco , Reino Unido/epidemiologia , Adulto Jovem
18.
J Epidemiol Community Health ; 73(12): 1063-1070, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31597672

RESUMO

BACKGROUND: Epidemiological studies have reported conflicting results in the association between Caesarean section (CS) birth and childhood obesity. Many of these studies had small sample sizes, were unable to distinguish between elective/planned and emergency CS, and did not adjust for the key confounder maternal pre-pregnancy body mass index (BMI). We investigated the association between CS delivery, particularly elective/planned and childhood obesity, using the Growing Up in New Zealand prospective longitudinal cohort study. METHODS: Pregnant women planning to deliver their babies on the New Zealand upper North Island were invited to participate. Mode of delivery was categorised into spontaneous vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS. The main outcome was childhood obesity defined according to the International Obesity Taskforce criteria at age 24 and 54 months. Multinomial logistic regression and mixed-effects linear regression models were fitted with associations adjusted for several potential confounders. RESULTS: Of the 6599 infants, 1532 (23.2%) were delivered by CS. At age 24 months, 478 (9.3%) children were obese. There was a statistically significant association between planned CS adjusted relative risk ratio (aRRR=1.59; (95% CI 1.09 to 2.33)) and obesity but not for emergency CS (aRRR=1.27; (95% CI 0.89 to 1.82)). At age 54 months there was no association between planned CS (aRRR=0.89; (95% CI 0.54 to 1.45)) and obesity as well as for emergency CS (aRRR=1.19; (95% CI 0.80 to 1.77)). At all-time points those born by planned CS had a higher mean BMI (adjusted mean difference=0.16; (95% CI 0.00 to 0.31), p=0.046). CONCLUSIONS: Planned CS was an independent predictor of obesity in early childhood. This suggests that birth mode influences growth, at least in the short term. This association occurred during a critical phase of human development, the first 2 years of life, and if causal might result in long-term detrimental cardiometabolic changes.

19.
Sci Rep ; 9(1): 13701, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548567

RESUMO

Prediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks' gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.

20.
BMJ Open ; 9(8): e031238, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401613

RESUMO

INTRODUCTION: To date, there is no robust enough test to predict small-for-gestational-age (SGA) infants, who are at increased lifelong risk of morbidity and mortality. OBJECTIVE: To determine the accuracy of metabolomics in predicting SGA babies and elucidate which metabolites are predictive of this condition. DATA SOURCES: Two independent researchers explored 11 electronic databases and grey literature in February 2018 and November 2018, covering publications from 1998 to 2018. Both researchers performed data extraction and quality assessment independently. A third researcher resolved discrepancies. STUDY ELIGIBILITY CRITERIA: Cohort or nested case-control studies were included which investigated pregnant women and performed metabolomics analysis to evaluate SGA infants. The primary outcome was birth weight <10th centile-as a surrogate for fetal growth restriction-by population-based or customised charts. STUDY APPRAISAL AND SYNTHESIS METHODS: Two independent researchers extracted data on study design, obstetric variables and sampling, metabolomics technique, chemical class of metabolites, and prediction accuracy measures. Authors were contacted to provide additional data when necessary. RESULTS: A total of 9181 references were retrieved. Of these, 273 were duplicate, 8760 were removed by title or abstract, and 133 were excluded by full-text content. Thus, 15 studies were included. Only two studies used the fifth centile as a cut-off, and most reports sampled second-trimester pregnant women. Liquid chromatography coupled to mass spectrometry was the most common metabolomics approach. Untargeted studies in the second trimester provided the largest number of predictive metabolites, using maternal blood or hair. Fatty acids, phosphosphingolipids and amino acids were the most prevalent predictive chemical subclasses. CONCLUSIONS AND IMPLICATIONS: Significant heterogeneity of participant characteristics and methods employed among studies precluded a meta-analysis. Compounds related to lipid metabolism should be validated up to the second trimester in different settings. PROSPERO REGISTRATION NUMBER: CRD42018089985.

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