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1.
PLoS One ; 15(8): e0238315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866202

RESUMO

BACKGROUND: In low resource settings recall of the date of the mother's last menstrual period may be unreliable and due to limited availability of prenatal ultrasound, gestational age of newborns may not be assessed reliably. Preterm babies are at high risk of morbidity and mortality so an alternative strategy is to identify them soon after birth is needed for early referral and management. OBJECTIVE: The objective of this study was to assess the accuracy in assessing prematurity of newborn, over and above birthweight, using a pictorial Simplified Gestational Age Score adapted for use as a Tablet App. METHODS: Two trained nurse midwives, blinded to each other's assessment and the actual gestational age of the baby used the app to assess gestational age at birth in 3 hospitals based on the following 4 parameters-newborn's posture, skin texture, breast and genital development. Inter-observer variation was evaluated and the optimal scoring cut-off to detect preterm birth was determined. Sensitivity and specificity of gestational age score using the tablet was estimated using combinations of last menstrual period and ultrasound as reference standards to assess preterm birth. The predictive accuracy of the score using the area under a receiver operating characteristic curve was also determined. To account for potential reference standard bias, we also evaluated the score using latent class models. RESULTS: A total of 8,591 live singleton births whose gestational age by last menstrual period and ultrasound was within 1 weeks of each other were enrolled. There was strong agreement between assessors (concordance correlation coefficient 0.77 (95% CI 0.76-0.78) and Fleiss' kappa was 0.76 (95% CI 0.76-0.78). The optimal cut-off for the score to predict preterm was 13. Irrespective of the reference standard, the specificity of the score was 90% and sensitivity varied from 40-50% and the predictive accuracy between 74%-79% for the reference standards. The likelihood ratio of a positive score varied between 3.75-4.88 while the same for a negative likelihood ratio consistently varied between 0.57-0.72. Latent class models showed similar results indicating no reference standard bias. CONCLUSION: Gestational age scores had strong inter-observer agreement, robust prediction of preterm births simplicity of use by nurse midwives and can be a useful tool in resource-limited scenarios. TRIAL REGISTRATION: The Tablet App for the Simplified Gestational Age Score (T-SGAS) study was registered at ClinicalTrials.gov NCT02408783.


Assuntos
Recém-Nascido Prematuro/fisiologia , Parto/fisiologia , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/fisiopatologia , Peso ao Nascer/fisiologia , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Aplicativos Móveis , Gravidez , Medição de Risco/métodos , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal/métodos
2.
PLoS Med ; 17(8): e1003271, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797061

RESUMO

BACKGROUND: Inflammation during pregnancy is hypothesized to influence fetal growth. Eicosanoids, an important class of lipid mediators derived from polyunsaturated fatty acids, can act as both direct influences and biomarkers of inflammation through a variety of biological pathways. However, quantifying these distinct inflammatory pathways has proven difficult. We aimed to characterize a comprehensive panel of plasma eicosanoids longitudinally across gestation in pregnant women and to determine whether levels differed by infant size at delivery. METHODS AND FINDINGS: Our data come from a case-control study of 90 pregnant women nested within the LIFECODES prospective birth cohort study conducted at Brigham and Women's Hospital in Boston, Massachusetts. This study included 31 women who delivered small for gestational age (SGA) babies (SGA, ≤10th percentile), 28 who delivered large for gestational age (LGA) babies (≥90th percentile), and 31 who delivered appropriate for gestational age (AGA) babies (controls, >10th to <90th percentile). All deliveries occurred between 2010 and 2017. Most participants were in their early 30s (median age: 33 years), of white (60%) or black (20%) race/ethnicity, and of normal pre-pregnancy BMI (median BMI: 23.5 kg/m2). Women provided non-fasting plasma samples during 3 prenatal study visits (at median 11, 25, and 35 weeks gestation) and were analyzed for a panel of eicosanoids. Eicosanoids were grouped by biosynthetic pathway, defined by (1) the fatty acid precursor, including linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA), and (2) the enzyme group, including cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). Additionally, the concentrations of the 4 fatty acids (LA, AA, DHA, and EPA) were measured in maternal plasma. Analytes represent lipids from non-esterified plasma. We examined correlations among eicosanoids and trajectories across pregnancy. Differences in longitudinal concentrations between case groups were examined using Bayesian linear mixed effects models, which included participant-specific random intercepts and penalized splines on gestational age. Results showed maternal plasma levels of eicosanoids and fatty acids generally followed U-shaped curve patterns across gestation. Bayesian models showed that associations between eicosanoids and case status varied by biosynthetic pathway. Eicosanoids derived from AA via the CYP and LOX biosynthetic pathways were positively associated with SGA. The adjusted mean concentration of 12-HETE, a LOX pathway product, was 56.2% higher (95% credible interval 6.6%, 119.1%) among SGA cases compared to AGA controls. Eicosanoid associations with LGA were mostly null, but negative associations were observed with eicosanoids derived from AA by LOX enzymes. The fatty acid precursors had estimated mean concentrations 41%-97% higher among SGA cases and 33%-39% lower among LGA cases compared to controls. Primary limitations of the study included the inability to explore the potential periods of susceptibility of eicosanoids on infant size due to limited sample size, along with the use of infant size at delivery instead of longitudinal ultrasound measures to estimate fetal growth. CONCLUSIONS: In this nested case-control study, we found that eicosanoids and fatty acids systematically change in maternal plasma over pregnancy. Eicosanoids from specific inflammation-related pathways were higher in mothers of SGA cases and mostly similar in mothers of LGA cases compared to controls. These findings can provide deeper insight into etiologic mechanisms of abnormal fetal growth outcomes.


Assuntos
Peso ao Nascer/fisiologia , Eicosanoides/sangue , Idade Gestacional , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Gravidez/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Estudos Prospectivos
3.
PLoS One ; 15(8): e0238169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853237

RESUMO

INTRODUCTION: Preterm birth is defined as all births before 37 completed weeks of gestation. Globally, the prevalence rate of preterm birth ranges from 47.5 to 137 per 1000 live births. In Ethiopia, the prevalence of preterm birth is 10.1%. Several anthropometric parameters, particularly, head circumference and foot length(FL) have been used as a proxy measure for gestational age(GA). OBJECTIVE: To assess the use of newborn foot length as a screening tool to identify preterm newborns and correlation factors at the University of Gondar Comprehensive Specialized Hospital (UOG CSH), Northwest Ethiopia. METHODS: Institutional based cross-sectional study design was conducted on 205 newborns admitted to a neonatal intensive care unit, UOG CSH. Systematic sampling technique was employed. Optimal cutoff newborn foot length and area under the curve (AUC) was calculated by the receiver operating characteristic curve analysis to assess the power of foot length measurement to diagnosis prematurity. RESULTS: The mean foot length was 7.41±0.67 cm with a range of 5.4-8.6 cm. Gestational age had a significant strong positive correlation with foot length(r = 0.865). The regression equation derived was GA = 4.5*FL + 3.61. Foot length had strong power (AUC = 0.99) to differentiate preterm from term newborns. A threshold newborn foot length of ≤7.35 cm had a sensitivity and specificity of 98.5% and 96.3%, respectively to predict prematurity. CONCLUSION: Foot length had a high sensitivity and specificity in identifying preterm newborns, making it a reliable tool to identify preterm birth in a rural setting.


Assuntos
Pé/fisiologia , Recém-Nascido Prematuro/fisiologia , Antropometria/métodos , Peso ao Nascer/fisiologia , Estudos Transversais , Países em Desenvolvimento , Etiópia , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Sensibilidade e Especificidade
4.
PLoS One ; 15(8): e0238223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853260

RESUMO

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.


Assuntos
Pressão Sanguínea/fisiologia , Retroalimentação Fisiológica/fisiologia , Glucocorticoides/sangue , Doenças da Hipófise/sangue , Doenças da Hipófise/fisiopatologia , Hipófise/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Masculino , Metirapona/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hipófise/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar
5.
PLoS One ; 15(8): e0237738, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817701

RESUMO

This study assessed within-trial cost-effectiveness of a shared care program (SC, n = 339) for pregnancy outcomes compared to usual care (UC, n = 361), as implemented in a randomized trial of Chinese women with gestational diabetes (GDM). SC consisted of an individualized dietary advice and physical activity counseling program. The UC was a one-time group education program. The effectiveness was measured by number needed to treat (NNT) to prevent one macrosomia/large for gestational age (LGA) infant. The cost-effectiveness was measured by incremental cost-effectiveness ratio in terms of cost (2012 Chinese Yuan/US dollar) per case of macrosomia and LGA prevented. The study took both a health care system and a societal perspective. This study found that the NNT was 16/14 for macrosomia/LGA. The incremental cost for treating a pregnant woman was ¥1,877 ($298) from a health care system perspective and ¥2,056 ($327) from a societal perspective. The cost of preventing a case of macrosomia/LGA from the two corresponding perspectives were ¥30,032/¥26,278 ($4,775/$4,178) and ¥32,896/¥28,784 ($5,230/$4,577), respectively. Considering the potential severe adverse health and economic consequences of a macrosomia/LGA infant, our findings suggest that implementing this lifestyle intervention for women with GDM is an efficient use of health care resources.


Assuntos
Análise Custo-Benefício , Diabetes Gestacional/economia , Glucose/metabolismo , Complicações na Gravidez/economia , Adulto , Peso ao Nascer/fisiologia , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/patologia , Exercício Físico/fisiologia , Feminino , Macrossomia Fetal , Educação em Saúde/normas , Estilo de Vida Saudável , Humanos , Recém-Nascido , Criança Pós-Termo , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/patologia , Resultado da Gravidez/epidemiologia
6.
PLoS Med ; 17(8): e1003305, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841251

RESUMO

BACKGROUND: Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. METHODS AND FINDINGS: Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits. CONCLUSIONS: We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.


Assuntos
Peso ao Nascer/fisiologia , Estatura/fisiologia , Estudo de Associação Genômica Ampla/métodos , Haplótipos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Testes Genéticos/métodos , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos
7.
PLoS One ; 15(6): e0233416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32502147

RESUMO

OBJECTIVE: To determine whether neighbourhood socioeconomic status (SES) was associated with large for gestational age (LGA) while considering key sociodemographic and clinical confounding factors. SETTING AND PATIENT: All singleton infants whose parents were living in the city of Marseilles, France, between 2013 and 2016. METHOD: Population-based study based on new-born hospital birth admission charts from the French National Uniform Hospital Discharge Data Set Database. LGA infants were compared to appropriate-for-gestational-age (AGA) infants. Multiple generalized logistic model analysis was used to examine factors associated with LGA. RESULTS: A total of 43,309 singleton infants were included, and 4,747 (11%) were born LGA. LGA infants were more likely to have metabolic and respiratory diseases and to be admitted to the neonatal intensive care unit. Multiparity, advanced maternal age, obesity and diabetes were associated with an increased risk of LGA. Lower neighbourhood SES was associated with LGA (aOR = 1.24, 95% CI: 1.14; 1.36; p<0.0001) independent of age, diabetes, obesity, maternal smoking and multiparity. The strength of this association increased with maternal age, reaching an aOR of 1.50 (95% CI: 1.26; 1.78; p<0.0001) for women > 35 years old. CONCLUSION: Neighbourhood SES could be considered an important factor for clinicians to better identify mothers at risk of having LGA births in addition to well-known risk factors such as maternal diabetes, obesity and age. The intensification of the association between SES and LGA with increasing maternal age suggests that neighbourhood disadvantage may act on LGA cumulatively over time.


Assuntos
Peso ao Nascer/fisiologia , Macrossomia Fetal/etiologia , Classe Social , Adulto , Índice de Massa Corporal , Diabetes Gestacional , Feminino , Macrossomia Fetal/economia , França , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Obesidade/complicações , Paridade , Gravidez , Complicações na Gravidez , Fatores de Risco , Fatores Socioeconômicos , Ganho de Peso/fisiologia
8.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32479590

RESUMO

Exploring factors that might affect nitrogen (N) efficiency in pigs could support the development of precision feeding concepts. Therefore, an experiment was conducted to determine the effects of birth weight (BiW) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in male pigs of 14 wk of age. BiW of the low BiW (LBW) and high BiW (HBW) pigs was 1.11 ± 0.14 and 1.79 ± 0.12 kg, respectively. Twenty LBW and 20 HBW pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design and fed restrictedly 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention in g/d was higher in the HBW than in the LBW pigs (P < 0.001). The N retention in g/(kg BW0.75·d) and N efficiency (= 100% × N retention / N intake), however, were not affected by BiW of the pigs. Moreover, fecal digestibility of N and urinary concentration of N and urea were not affected by BiW of the pigs. The concentration of insulin (P = 0.08) and insulin-like growth factor-1 (IGF-1;P = 0.05) in blood plasma was higher in HBW pigs, whereas the concentration of α-amino N tended to be lower in HBW pigs (P = 0.06). The LBW and HBW pigs could not be discriminated based on the plasma and urinary metabolites retrieved by nontargeted metabolomics. Restricting dietary protein supply decreased N retention (P < 0.001), N efficiency (P = 0.07), fecal N digestibility (P < 0.001), urinary concentration of N and urea (P < 0.001), and concentration of urea (P < 0.001), IGF-1 (P < 0.001), and α-amino N (P < 0.001) in blood plasma. The plasma and urinary metabolites differing between dietary protein regime were mostly amino acids (AA) or their derivatives, metabolites of the tricarboxylic acid cycle, and glucuronidated compounds, almost all being higher in the pigs fed the A regime. This study shows that BiW affects absolute N retention but does not affect N efficiency in growing pigs. Therefore, in precision feeding concepts, BiW of pigs should be considered as a factor determining protein deposition capacity but less as a trait determining N efficiency.


Assuntos
Peso ao Nascer/fisiologia , Proteínas na Dieta/administração & dosagem , Nitrogênio/metabolismo , Suínos/crescimento & desenvolvimento , Aminoácidos/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Proteínas na Dieta/metabolismo , Fezes/química , Masculino , Suínos/sangue , Suínos/fisiologia , Suínos/urina , Ureia/sangue
9.
PLoS One ; 15(6): e0235113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574213

RESUMO

OBJECTIVES: Timely delivery of fetal growth restriction (FGR) is important in reducing stillbirth. However, targeted earlier delivery of FGR preferentially removes smaller babies from later gestations, thereby right-shifting the distribution of birthweights at term. This artificially increases the birthweight cutoffs defining the lower centiles and redefines normally grown babies as small by population-based birthweight centiles. Our objective was to compare updated Australian national population-based birthweight centile charts over time with the prescriptive INTERGROWTH-21st standard. METHODS: A retrospective descriptive study of all singleton births ≥34 weeks' gestation in Victoria, Australia in five two-year epochs: 1983-84, 1993-94, 2003-04, 2013-14, and 2016-17. The birthweight cutoffs defining the 3rd and 10th centile from three Australian national population-based birthweight centile charts, for births in 1991-1994, in 1998-2007, and 2004-2013 respectively, were applied to each epoch to calculate the proportion of babies with birthweight <3rd and <10th centile. The same analysis was done using the INTERGROWTH-21st birthweight standard. To assess change over gestation, proportions were also calculated at preterm, early term and late term gestations. RESULTS: From 1983-84 to 2016-17, the proportion of babies with birthweight <3rd fell across all birthweight centile charts, from 3.1% to 1.7% using the oldest Australian chart, from 3.9% to 1.9% using the second oldest Australian chart, from 4.3% to 2.2% using the most recent Australian chart, and from 2.0% to 0.9% using the INTERGROWTH-21st standard. A similar effect was evident for the <10th centile. The effect was most obvious at term gestations. Updating the Australian population birthweight chart progressively right-shifted the birthweight distribution, changing the definition of small over time. The birthweight distribution of INTERGROWTH-21st was left-shifted compared to the Australian charts. CONCLUSIONS: Locally-derived population-based birthweight centiles are better for clinical audit of care but should not be updated. Prescriptive birthweight standards are less useful in defining 'small' due to their significant left-shift.


Assuntos
Peso ao Nascer/fisiologia , Retardo do Crescimento Fetal/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Natimorto/epidemiologia , Feminino , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Masculino , Vigilância da População/métodos , Gravidez , Estudos Retrospectivos , Vitória/epidemiologia
10.
PLoS One ; 15(4): e0232155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353068

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is a common condition, often associated with high maternal and fetal morbidity. The use of new tools for early GDM screening can contribute to metabolic control to reduce maternal and fetal risk. This study aimed to ascertain whether maternal visceral adipose tissue (VAT) measurement by ultrasound during the first half of pregnancy can predict the occurrence of GDM during the third trimester. METHODS: A prospective cohort study of 133 pregnant women with gestational age ≤20 weeks in an outpatient setting. VAT depth was measured by ultrasound at the maternal periumbilical region. GDM status was obtained through hospital charts during hospitalization to delivery. A Receiver Operator Characteristic (ROC) curve was used to determine the optimum threshold to predict GDM. RESULTS: According to the ROC curve, a 45mm threshold was identified as the best cut-off value, with 66% of accuracy to predict GDM. Crude and adjusted odds ratios (OR) for GDM were 13.4 (95%CI 2.9-61.1) and 8.9 (95%CI 1.9-42.2), respectively. A similar result was obtained among pre-gravid non-obese women, with crude and adjusted OR of 16.6 (95%CI 1.9-142.6) and 14.4 (95%CI 1.7-125.7), respectively. Among pre-gravid obese patients, a 45mm threshold did not reach statistical significance to predict GDM. CONCLUSION: The high and significant OR found before and after adjustments provides additional evidence of a strong association between VAT and GDM. It appears that VAT measurement during the first half of pregnancy has great potential in identifying non-obese women at high risk for GDM. This evidence can assist obstetricians in correctly allocating resources among populations of pregnant women at risk, determined not only by pre-gravid body mass index (BMI).


Assuntos
Diabetes Gestacional/etiologia , Gordura Intra-Abdominal/fisiopatologia , Adulto , Peso ao Nascer/fisiologia , Índice de Massa Corporal , Feminino , Idade Gestacional , Humanos , Obesidade/complicações , Gravidez , Gestantes , Estudos Prospectivos , Fatores de Risco
11.
Ann Allergy Asthma Immunol ; 125(3): 280-286.e5, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387533

RESUMO

BACKGROUND: Cesarean delivery (C-section) may influence the infant microbiome and affect immune system development and subsequent risk for allergic rhinitis (AR). OBJECTIVE: To investigate the association between C-section and AR at ages 6, 8, and 10 years. METHODS: Data were collected prospectively through Kaiser Permanente Northern Californias (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital and remained in the KPNC system for minimum 6 years (n = 117,768 age 6; n = 75,115 age 8; n = 40,332 age 10). Risk ratios (RR) for C-section and AR were estimated at each follow-up age and adjusted for important covariates, including intrapartum antibiotics, pre-pregnancy body mass index, maternal allergic morbidities, and breastfeeding. Subanalyses considered information on C-section indication, labor, and membrane rupture. RESULTS: After adjusting for confounders, we did not observe an association between C-section and AR at follow-up ages 6, 8, or 10 years (RR [CI]: 6 years, 0.98 [0.91, 1.04]; 8 years, 1.00 [0.95, 1.07]; 10 years, 1.03 [0.96, 1.10]). In stratified analyses, there was limited evidence that C-section increases the risk of AR in certain subgroups (eg, children of non-atopic mothers, second or higher birth order children), but most estimated risk ratios were consistent with no association. Estimated associations were unaffected by participant attrition, missing data, or intrapartum antibiotics. CONCLUSION: C-section delivery was not associated with AR at follow-up ages of 6, 8, or 10 years in a large contemporary US cohort.


Assuntos
Cesárea/efeitos adversos , Rinite Alérgica/etiologia , Adulto , Peso ao Nascer/imunologia , Peso ao Nascer/fisiologia , Aleitamento Materno/métodos , Criança , Feminino , Humanos , Masculino , Mães , Gravidez , Rinite Alérgica/imunologia , Risco , Adulto Jovem
12.
PLoS Med ; 17(5): e1003126, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32442232

RESUMO

BACKGROUND: Fetal growth in gestational diabetes mellitus (GDM) is directly linked to maternal glycaemic control; however, this relationship may be altered by oral anti-hyperglycaemic agents. Unlike insulin, such drugs cross the placenta and may thus have independent effects on fetal or placental tissues. We investigated the association between GDM treatment and fetal, neonatal, and childhood growth. METHODS AND FINDINGS: PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov, and Cochrane databases were systematically searched (inception to 12 February 2020). Outcomes of GDM-affected pregnancies randomised to treatment with metformin, glyburide, or insulin were included. Studies including preexisting diabetes or nondiabetic women were excluded. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Maternal outcome measures were glycaemic control, weight gain, and treatment failure. Offspring anthropometric parameters included fetal, neonatal, and childhood weight and body composition data. Thirty-three studies (n = 4,944), from geographical locations including Europe, North Africa, the Middle East, Asia, Australia/New Zealand, and the United States/Latin America, met eligibility criteria. Twenty-two studies (n = 2,801) randomised women to metformin versus insulin, 8 studies (n = 1,722) to glyburide versus insulin, and 3 studies (n = 421) to metformin versus glyburide. Eleven studies (n = 2,204) reported maternal outcomes. No differences in fasting blood glucose (FBS), random blood glucose (RBS), or glycated haemoglobin (HbA1c) were reported. No studies reported fetal growth parameters. Thirty-three studies (n = 4,733) reported birth weight. Glyburide-exposed neonates were heavier at birth (58.20 g, 95% confidence interval [CI] 10.10-106.31, p = 0.02) with increased risk of macrosomia (odds ratio [OR] 1.38, 95% CI 1.01-1.89, p = 0.04) versus neonates of insulin-treated mothers. Metformin-exposed neonates were born lighter (-73.92 g, 95% CI -114.79 to -33.06 g, p < 0.001) with reduced risk of macrosomia (OR 0.60, 95% CI 0.45-0.79, p < 0.001) than insulin-exposed neonates. Metformin-exposed neonates were born lighter (-191.73 g, 95% CI -288.01 to -94.74, p < 0.001) with a nonsignificant reduction in macrosomia risk (OR 0.32, 95% CI 0.08-1.19, I2 = 0%, p = 0.09) versus glyburide-exposed neonates. Glyburide-exposed neonates had a nonsignificant increase in total fat mass (103.2 g, 95% CI -3.91 to 210.31, p = 0.06) and increased abdominal (0.90 cm, 95% CI 0.03-1.77, p = 0.04) and chest circumferences (0.80 cm, 95% CI 0.07-1.53, p = 0.03) versus insulin-exposed neonates. Metformin-exposed neonates had decreased ponderal index (-0.13 kg/m3, 95% CI -0.26 to -0.00, p = 0.04) and reduced head (-0.21, 95% CI -0.39 to -0.03, p = 0.03) and chest circumferences (-0.34 cm, 95% CI -0.62 to -0.05, p = 0.02) versus the insulin-treated group. Metformin-exposed neonates had decreased ponderal index (-0.09 kg/m3, 95% CI -0.17 to -0.01, p = 0.03) versus glyburide-exposed neonates. Study limitations include heterogeneity in dosing, heterogeneity in GDM diagnostic criteria, and few studies reporting longitudinal growth outcomes. CONCLUSIONS: Maternal randomisation to glyburide resulted in heavier neonates with a propensity to increased adiposity versus insulin- or metformin-exposed groups. Metformin-exposed neonates were lighter with reduced lean mass versus insulin- or glyburide-exposed groups, independent of maternal glycaemic control. Oral anti-hyperglycaemics cross the placenta, so effects on fetal anthropometry could result from direct actions on the fetus and/or placenta. We highlight a need for further studies examining the effects of intrauterine exposure to antidiabetic agents on longitudinal growth, and the importance of monitoring fetal growth and maternal glycaemic control when treating GDM. This review protocol was registered with PROSPERO (CRD42019134664/CRD42018117503).


Assuntos
Glicemia/análise , Diabetes Gestacional/tratamento farmacológico , Macrossomia Fetal/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Antropometria/métodos , Peso ao Nascer/fisiologia , Diabetes Gestacional/sangue , Feminino , Glibureto/efeitos adversos , Glibureto/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Gravidez
13.
Eur J Epidemiol ; 35(7): 685-697, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32383070

RESUMO

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.


Assuntos
Peso ao Nascer , Pressão Sanguínea/genética , Hipertensão/epidemiologia , Hipertensão/genética , Análise da Randomização Mendeliana/métodos , Adulto , Peso ao Nascer/genética , Peso ao Nascer/fisiologia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Polimorfismo de Nucleotídeo Único/genética
14.
Lancet Diabetes Endocrinol ; 8(6): 501-510, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32445737

RESUMO

BACKGROUND: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight. METHODS: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496. FINDINGS: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT4]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (pinteraction=0·10). Each 1 SD increase in FT4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second. INTERPRETATION: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy. FUNDING: Netherlands Organization for Scientific Research (grant 401.16.020).


Assuntos
Peso ao Nascer/fisiologia , Hipotireoidismo/fisiopatologia , Complicações na Gravidez/fisiopatologia , Glândula Tireoide/fisiologia , Glândula Tireoide/fisiopatologia , Feminino , Idade Gestacional , Humanos , Hipotireoidismo/complicações , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Gravidez , Testes de Função Tireóidea/tendências
15.
J Appl Oral Sci ; 28: e20190351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236354

RESUMO

INTRODUCTION: Excessive weight is associated with periodontitis because of inflammatory mediators secreted by the adipose tissue. Periodontal impairments can occur during pregnancy due to association between high hormonal levels and inadequate oral hygiene. Moreover, periodontitis and excessive weight during pregnancy can negatively affect an infant's weight at birth. OBJECTIVE: This observational, cross-sectional study aimed to evaluate the association between pre-pregnancy overweight/obesity, periodontitis during the third trimester of pregnancy, and the infants' birth weight. METHODOLOGY: The sample set was divided into 2 groups according to the preconception body mass index: obesity/overweight (G1=50) and normal weight (G2=50). Educational level, monthly household income, and systemic impairments during pregnancy were assessed. Pocket probing depth (PPD) and clinical attachment level (CAL) were obtained to analyze periodontitis. The children's birth weight was classified as low (<2.5 kg), insufficient (2.5-2.999 kg), normal (3-3.999 kg), or excessive (≥4 kg). Bivariate analysis (Mann-Whitney U test, t-test, chi-squared test) and logistic regression (stepwise backward likelihood ratio) were performed (p<0.05). RESULTS: G1 showed lower socioeconomic levels and higher prevalence of arterial hypertension and gestational diabetes mellitus during pregnancy than G2 (p=0.002). G1 showed higher means of PPD and CAL (p=0.041 and p=0.039, respectively) and therefore a higher prevalence of periodontitis than G2 (p=0.0003). G1 showed lower infants' birth weight than G2 (p=0.0004). Excessive maternal weight and educational levels were independent variables associated with periodontitis during the third trimester of pregnancy (X2[2]=23.21; p<0.0001). Maternal overweight/obesity was also associated with low/insufficient birth weight (X2[1]=7.01; p=0.008). CONCLUSION: The present findings suggest an association between excessive pre-pregnancy weight, maternal periodontitis, and low/insufficient birth weight.


Assuntos
Peso ao Nascer/fisiologia , Recém-Nascido de Baixo Peso/fisiologia , Obesidade Materna/fisiopatologia , Periodontite/fisiopatologia , Terceiro Trimestre da Gravidez/fisiologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Diabetes Gestacional/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Gravidez , Resultado da Gravidez , Fatores Socioeconômicos , Estatísticas não Paramétricas , Adulto Jovem
16.
PLoS One ; 15(3): e0230426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231377

RESUMO

OBJECTIVE: Postnatal vitamin D supplementation is standard of care in neonates and preterm infants. Despite routine supplementation of vitamin D, a wide range of complications related to vitamin D deficiency has been described in the literature. Since standard vitamin D supplementation might be not sufficient in preterm infants with a genetic predisposition for vitamin D deficiency, we investigated the outcome of preterm infants with regard to their genetic estimated vitamin D levels. METHODS: Preterm infants with a birth weight below 1500 grams were included in the German Neonatal Network at the time of their birth and tested at the age of five. The vitamin D level was genetically calculated based on three single nucleotide polymorphisms (SNPs: rs12794714, rs7944926 and rs2282679) which alter vitamin D synthesis pathways. Specific alleles of these polymorphisms are validated markers for low plasma vitamin D levels. Outcome data were based on baseline data at the time of birth, typical complications of prematurity, body measurements at the age of five and occurrence of bone fractures. T-test and Fisher's exact test were used for statistical comparison. RESULTS: According to their genetic predisposition, 1,924 preterm infants were divided into groups of low (gsVitD < 20. Percentile), intermediate and high vitamin D level estimates. Low genetic vitamin D level estimates could not be shown to be associated with any adverse outcome measures examined. The analyses covered data on aforementioned determinants. CONCLUSION: Low genetic vitamin D level estimates could not be shown to be associated with previously described adverse outcome in preterm infants.


Assuntos
Predisposição Genética para Doença , Recém-Nascido de muito Baixo Peso/metabolismo , Deficiência de Vitamina D/genética , Vitamina D/metabolismo , Peso ao Nascer/fisiologia , Estudos de Coortes , Suplementos Nutricionais , Feminino , Fraturas Ósseas , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido Prematuro/metabolismo , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Masculino , Vitamina D/genética , Deficiência de Vitamina D/metabolismo
17.
Rev Bras Epidemiol ; 23: e200004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130393

RESUMO

INTRODUCTION: Epidemiological studies have shown associations between placental measurements and perinatal and later life outcomes. OBJECTIVES: To report placental measurements and evaluate their association with birth weight in a Brazilian birth cohort. METHODS: Retrospective cohort study with 958 mothers, placentas, and newborns delivered at the Ribeirão Preto Medical School Hospital, Universidade de São Paulo, Brazil, in 2010 and 2011. The information was collected from interviews, medical records, and pathology reports. The placental measurements were: weight, largest and smallest diameters, eccentricity, thickness, shape, area, and birth weight/placental weight and placental weight/birth weight ratios. We analyzed the associations between birth weight and placental measurements using multiple linear regression. RESULTS: Placental weight alone accounted for 48% of birth weight variability (p < 0.001), whereas placental measurements combined (placental weight, largest and smallest diameters, and thickness) were responsible for 50% (p < 0.001). When adjusted for maternal and neonatal characteristics, placental measurements explained 74% of birth weight variability (p < 0.001). CONCLUSION: Placental measurements are powerful independent predictors of birth weight. Placental weight is the most predictive of them, followed by the smallest diameter.


Assuntos
Peso ao Nascer/fisiologia , Placenta/anatomia & histologia , Adulto , Índice de Massa Corporal , Brasil , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Análise Multivariada , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Fertil Steril ; 113(4): 745-752, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32147172

RESUMO

OBJECTIVE: To investigate whether endometrial thickness (EMT) is associated with adverse obstetric and neonatal outcomes in fresh in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. DESIGN: Retrospective cohort study. SETTING: University-based reproductive medical center. PATIENT(S): Women under the age of 42 years who underwent IVF/ICSI treatment and received fresh ET in our unit from January 2017 to December 2018, resulting in a live singleton birth. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF/ICSI; fresh ET. MAIN OUTCOME MEASURE(S): Birth weight, gestational age, small for gestational age (SGA), large for gestational age (LGA), placenta previa, placental abruption, hypertensive disorders, and gestational diabetes mellitus. RESULT(S): The risk of being born SGA was statistically significantly increased in the EMT ≤7.5 mm group compared with those from the EMT >12 mm group (adjusted odds ratio [aOR] 2.391; 95% confidence interval [CI], 1.155-4.950). Moreover, maternal body mass index, secondary infertility, preterm delivery, and hypertensive disorders were all independent predictors for SGA. The mean birth weights of singletons in women with EMT ≤7.5 mm were lower than in the groups with EMT >7.5-12 mm and EMT >12 mm (3.25 ± 0.56 kg vs. 3.38 ± 0.51 kg and 3.39 ± 0.53 kg, respectively). CONCLUSION(S): After fresh IVF/ICSI-ET, the risk of SGA was increased twofold in women with EMT ≤7.5 mm compared with women with EMT >12 mm. We suggest that women with a thin EMT after obtaining a pregnancy by IVF should receive improved prenatal care to reduce the risk of delivering a SGA infant.


Assuntos
Transferência Embrionária/efeitos adversos , Endométrio/diagnóstico por imagem , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Nascimento Vivo/epidemiologia , Injeções de Esperma Intracitoplásmicas/tendências , Adulto , Peso ao Nascer/fisiologia , Estudos de Coortes , Transferência Embrionária/tendências , Endométrio/patologia , Feminino , Fertilização In Vitro/efeitos adversos , Fertilização In Vitro/tendências , Humanos , Recém-Nascido , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/efeitos adversos
20.
Obesity (Silver Spring) ; 28(3): 647-654, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012478

RESUMO

OBJECTIVE: The aims of this study are to examine the potential association between grandmaternal BMI and grandchild's birth weight (BW) and whether maternal BW and BMI mediate this association. METHODS: Data of 209 grandmother-mother pairs and 355 grandchildren from the Isle of Wight birth cohort in the UK were analyzed using path analysis. RESULTS: An indirect effect of grandmaternal BMI on increasing grandchild's BW was mediated by maternal BW and BMI at age 18 years (indirect effects: ß = 2.3 g/unit increase in grandmaternal BMI via maternal BW and ß = 4.4 g via maternal BMI; P = 0.04). These two mediating effects of maternal BW and BMI confounded one another. Grandmaternal smoking during pregnancy had an indirect effect on decreasing grandchild's BW, dependent on maternal smoking during pregnancy and BW (indirect effects: ß = -36.1 g compared with nonsmoking grandmothers via maternal smoking during pregnancy and ß = -27.2 g via maternal BW; P = 0.005). Neither direct effect between grandmaternal BMI and grandchild's BW nor that between grandmaternal smoking during pregnancy and grandchild's BW was statistically significant. CONCLUSIONS: Larger grandmaternal BMI indirectly increased grandchild's BW via maternal BW and BMI. Grandmaternal smoking during pregnancy indirectly reduced grandchild's BW via maternal smoking during pregnancy and BW.


Assuntos
Peso ao Nascer/fisiologia , Índice de Massa Corporal , Avós/psicologia , Feminino , Humanos , Masculino , Gravidez
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