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1.
BMC Pregnancy Childbirth ; 21(1): 96, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514342

RESUMO

BACKGROUND: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). METHODS: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. RESULTS: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. CONCLUSIONS: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Retardo do Crescimento Fetal/etiologia , Macrossomia Fetal/etiologia , Gráficos de Crescimento , Neonatologia/normas , Adulto , Peso ao Nascer , Diabetes Mellitus Tipo 1/terapia , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/epidemiologia , Macrossomia Fetal/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Modelos Logísticos , Masculino , Gravidez , Nascimento Prematuro , Reino Unido
2.
BJOG ; 128(1): 77-85, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32588532

RESUMO

OBJECTIVE: Exploring associations between antenatal detection of fetal growth restriction (FGR) and adverse outcome. DESIGN: Retrospective, observational, register-based study. SETTING: Zealand, Denmark. POPULATION OR SAMPLE: Children born from 1 September 2012 to 31 August 2015. METHODS: Diagnoses from birth until 1 January 2018 were retrieved from The National Patient Registry. Detection was defined as estimated fetal weight less than the 2.3rd centile. Cox regression was used to associate detection status with the hazard rate of adverse outcome, adjusted for fetal weight deviation, maternal age, ethnicity, body mass index and smoking. MAIN OUTCOME MEASURES: Adverse neonatal outcome, adverse neuropsychiatric outcome, respiratory disorders, endocrine disorders, gastrointestinal/urogenital disorders. RESULTS: A total of 2425 FGR children were included. An association was found for gastrointestinal/urogenital disorders (hazard ratio [HR] 1.68, 95% CI 1.26-2.23, P < 0.001) and respiratory disorders (HR 1.22, 95% CI 1.02-1.46, P = 0.03) in detected versus undetected infants. For adverse neuropsychiatric outcome, HR was 1.32 (95% CI 1.00-1.75, P = 0.05). There was no evidence of an association between detection and adverse neonatal outcome (HR 1.00, 95% CI 0.62-1.61, P = 0.99) and endocrine disorders (HR 1.39, 95% CI 0.88-2.19, P = 0.16). Detected infants were smaller (median -28% versus -25%, P < 0.0001), more often born preterm (odds ratio [OR] 4.15, 3.12-5.52, P < 0.0001) and more often born after induction or caesarean section (OR 5.19, 95% CI 4.13-6.51, P < 0.0001). Stillbirth risk was increased in undetected FGR fetuses (OR 2.63, 95% CI 1.37-5.04, P = 0.004). CONCLUSIONS: We found an association between detection of FGR and risk of adverse childhood conditions, possibly caused by prematurity. Iatrogenic prematurity may be inevitable in stillbirth prevention, but is accompanied by a risk of long-term childhood conditions. TWEETABLE ABSTRACT: Antenatal detection of growth-restricted fetuses is associated with adverse childhood outcomes but fewer intrauterine deaths.


Assuntos
Retardo do Crescimento Fetal/epidemiologia , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Adulto , Dinamarca/epidemiologia , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/etiologia , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Sistema de Registros , Estudos Retrospectivos , Natimorto , Ultrassonografia Pré-Natal
3.
BMC Med ; 18(1): 395, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357243

RESUMO

BACKGROUND: Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight < 10th centile) is a commonly used proxy for FGR, detection of FGR among appropriate-for-gestational-age (AGA; weight ≥ 10th centile) fetuses remains an unmet need in clinical care. We aimed to determine whether reduced antenatal growth velocity from the time of routine mid-trimester ultrasound is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency among term AGA infants. METHODS: Three hundred and five women had biometry measurements recorded from their routine mid-trimester (20-week) ultrasound, at 28 and 36 weeks' gestation, and delivered an AGA infant. Mid-trimester, 28- and 36-week estimated fetal weight (EFW) and abdominal circumference (AC) centiles were calculated. The EFW and AC growth velocities between 20 and 28 weeks, and 20-36 weeks, were examined as predictors of four clinical indicators of placental insufficiency: (i) low 36-week cerebroplacental ratio (CPR; CPR < 5th centile reflects cerebral redistribution-a fetal adaptation to hypoxia), (ii) neonatal acidosis (umbilical artery pH < 7.15) after the hypoxic challenge of labour, (iii) low neonatal body fat percentage (BF%) reflecting reduced nutritional reserve and (iv) placental weight < 10th centile. RESULTS: Declining 20-36-week fetal growth velocity was associated with all indicators of placental insufficiency. Each one centile reduction in EFW between 20 and 36 weeks increased the odds of cerebral redistribution by 2.5% (odds ratio (OR) = 1.025, P = 0.001), the odds of neonatal acidosis by 2.7% (OR = 1.027, P = 0.002) and the odds of a < 10th centile placenta by 3.0% (OR = 1.030, P < 0.0001). Each one centile reduction in AC between 20 and 36 weeks increased the odds of neonatal acidosis by 3.1% (OR = 1.031, P = 0.0005), the odds of low neonatal BF% by 2.8% (OR = 1.028, P = 0.04) and the odds of placenta < 10th centile by 2.1% (OR = 1.021, P = 0.0004). Falls in EFW or AC of > 30 centiles between 20 and 36 weeks were associated with two-threefold increased relative risks of these indicators of placental insufficiency, while low 20-28-week growth velocities were not. CONCLUSIONS: Reduced growth velocity between 20 and 36 weeks among AGA fetuses is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency. These fetuses potentially represent an important, under-recognised cohort at increased risk of stillbirth. Encouragingly, this novel fetal assessment would require only one additional ultrasound to current routine care, and adds to the potential benefits of routine 36-week ultrasound.


Assuntos
Adaptação Fisiológica/fisiologia , Desenvolvimento Fetal/fisiologia , Retardo do Crescimento Fetal/etiologia , Peso Corporal Ideal , Insuficiência Placentária , Segundo Trimestre da Gravidez/fisiologia , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/epidemiologia , Peso Fetal/fisiologia , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Insuficiência Placentária/diagnóstico , Insuficiência Placentária/epidemiologia , Insuficiência Placentária/fisiopatologia , Gravidez , Fatores de Risco , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagem , Adulto Jovem
4.
PLoS One ; 15(9): e0239477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956426

RESUMO

OBJECTIVE: Report maternal, fetal and neonatal complications associated with single intrauterine fetal death (sIUFD) in monochorionic twin pregnancies. DESIGN: Prospective observational study. SETTING: UK. POPULATION: 81 monochorionic twin pregnancies with sIUFD after 14 weeks gestation, irrespective of cause. METHODS: UKOSS reporters submitted data collection forms using data from hospital records. MAIN OUTCOME MEASURES: Aetiology of sIUFD; surviving co-twin outcomes: perinatal mortality, central nervous system (CNS) imaging, gestation and mode of delivery, neonatal outcomes; post-mortem findings; maternal outcomes. RESULTS: The commonest aetiology was twin-twin transfusion syndrome (38/81, 47%), "spontaneous" sIUFD (22/81, 27%) was second commonest. Death of the co-twin was common (10/70, 14%). Preterm birth (<37 weeks gestation) was the commonest adverse outcome (77%): half were spontaneous and half iatrogenic. Only 46/75 (61%) cases had antenatal CNS imaging, of which 33 cases had known results of which 7/33 (21%) had radiological findings suggestive of neurological damage. Postnatal CNS imaging revealed an additional 7 babies with CNS abnormalities, all born at <36 weeks, including all 4 babies exhibiting abnormal CNS signs. Major maternal morbidity was relatively common, with 6% requiring ITU admission, all related to infection. CONCLUSIONS: Monochorionic twin pregnancies with single IUD are complex and require specialist care. Further research is required regarding optimal gestation at delivery of the surviving co-twin, preterm birth prevention, and classifying the cause of death in twin pregnancies. Awareness of the importance of CNS imaging, and follow-up, needs improvement.


Assuntos
Morte Fetal , Gêmeos Monozigóticos , Adulto , Corioamnionite/epidemiologia , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/mortalidade , Transfusão Feto-Fetal/mortalidade , Transfusão Feto-Fetal/terapia , Idade Gestacional , Humanos , Incidência , Lactente , Mortalidade Infantil , Recém-Nascido , Nascimento Vivo , Masculino , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/embriologia , Malformações do Sistema Nervoso/epidemiologia , Mortalidade Perinatal , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Redução de Gravidez Multifetal , Gravidez de Gêmeos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Transtornos Puerperais/epidemiologia , Reino Unido/epidemiologia
5.
PLoS One ; 15(9): e0239030, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915914

RESUMO

Hemopexin and α1-microglobulin act as scavengers to eliminate free heme-groups responsible for hemoglobin-induced oxidative stress. The present study evaluated maternal and fetal plasma concentrations of these scavengers in the different phenotypes of placenta-mediated disorders. Singleton pregnancies with normotensive fetal growth restriction [FGR] (n = 47), preeclampsia without FGR (n = 45) and preeclampsia with FGR (n = 51) were included prospectively as well as uncomplicated pregnancies (n = 49). Samples were collected at delivery and ELISA analysis was applied to measure the hemopexin and α1-microglobulin concentrations. In maternal blood in preeclampsia with and without FGR, hemopexin was significantly lower (p = 0.003 and p<0.001, respectively) and α1-microglobulin was significantly higher (p<0.001 in both) whereas no difference existed in normotensive FGR mothers compared to controls. In contrast, in fetal blood in growth restricted fetuses with and without preeclampsia, both hemopexin and α1-microglobulin were significantly lower (p<0.001 and p = 0.001 for hemopexin, p = 0.016 and p = 0.013 for α1-microglobulin, respectively) with no difference in fetuses from preeclampsia without FGR in comparison to controls. Thus, hemopexin and α1-microglobulin present significantly altered concentrations in maternal blood in the maternal disease -preeclampsia- and in cord blood in the fetal disease -FGR-, which supports their differential role in placenta-mediated disorders in accordance with the clinical presentation of these disorders.


Assuntos
alfa-Globulinas/metabolismo , Retardo do Crescimento Fetal/sangue , Heme/metabolismo , Hemopexina/metabolismo , Pré-Eclâmpsia/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Sangue Fetal/metabolismo , Retardo do Crescimento Fetal/etiologia , Depuradores de Radicais Livres/sangue , Humanos , Recém-Nascido , Estresse Oxidativo , Pré-Eclâmpsia/etiologia , Gravidez , Estudos Prospectivos
6.
PLoS One ; 15(7): e0235840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702025

RESUMO

OBJECTIVES: Maternal protein malnutrition is associated with impaired fetal growth, and lifetime consequences for the offspring. Our group has previously developed a model of protein-restriction in the non-human primate, which was associated with fetal growth restriction, stillbirth, decreased placental perfusion, and evidence of fetal hypoxia, suggesting perturbed vascular development. Our objective was to histologically characterize the micro-anatomic alterations associated with adverse pregnancy outcomes taking an approach that permits investigation of the 3D vascular structure and surrounding histology without the requirement for 3D vascular casting or relying on 2D stereology which both have methodological limitations. METHODS: Rhesus macaques were assigned in the pre-gestational period to a control diet that contained 26% protein, or study diet containing 13% protein (50% PR diet). Placental tissue was collected at delivery and processed using a clarification, immunohistochemistry, and confocal microscopy protocol published previously by our group. Three dimensional reconstructions and quantitative assessment of the vascular micro-anatomy was performed using analysis software (Imaris®) and statistical analysis accounted for maternal and fetal confounders. RESULTS: In unadjusted analysis, when comparing those pregnancies on a 50% PR diet (n = 4) with those on a control diet (n = 4), protein-restriction diet was associated with decreased maternal pre-pregnancy weight (difference of -1.975kg, 95% CI -3.267 to -0.6826). When controlling for maternal pre-pregnancy weight, fetal sex, and latency from tissue collection to imaging, a gestational protein-restriction diet was associated with decreases in total vascular length, total vascular surface area, total vascular volume, and vascular density. CONCLUSION: In this pilot study, a gestational protein-restriction diet altered the placental micro-vasculature with decreased vascular caliber and density, which may be related to the observed adverse pregnancy outcomes and perturbed placental perfusion previously demonstrated in this model.


Assuntos
Dieta com Restrição de Proteínas/efeitos adversos , Retardo do Crescimento Fetal/patologia , Transtornos da Nutrição Fetal/patologia , Placenta/patologia , Animais , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal/etiologia , Transtornos da Nutrição Fetal/etiologia , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Macaca mulatta/embriologia , Macaca mulatta/fisiologia , Projetos Piloto , Circulação Placentária , Gravidez , Natimorto
7.
JAMA Netw Open ; 3(6): e205323, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32585017

RESUMO

Importance: Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective: To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants: This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions: Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures: The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results: Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008). Conclusions and Relevance: These findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT02277132.


Assuntos
Peso ao Nascer , Término Precoce de Ensaios Clínicos , Retardo do Crescimento Fetal/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Doenças Placentárias/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Retardo do Crescimento Fetal/etiologia , Idade Gestacional , Humanos , Hipertensão Pulmonar/induzido quimicamente , Recém-Nascido , Doenças do Recém-Nascido/induzido quimicamente , Doenças do Recém-Nascido/prevenção & controle , Análise de Intenção de Tratamento , Masculino , Artéria Cerebral Média/fisiologia , Mortalidade Perinatal , Inibidores da Fosfodiesterase 5/efeitos adversos , Doenças Placentárias/fisiopatologia , Pré-Eclâmpsia/etiologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Fluxo Pulsátil , Citrato de Sildenafila/efeitos adversos , Artérias Umbilicais/fisiologia
8.
Arch Gynecol Obstet ; 302(1): 31-45, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445067

RESUMO

PURPOSE: The use of assisted reproductive technology (ART) has increased in the last 2 decades and continuous surveillance is needed. This systematic review aims to assess the risk of adverse neonatal outcomes (preterm birth [PTB], low birth weight [LBW], small-for-gestationalage [SGA] and large for gestational-age [LGA]), in singleton pregnancies conceived by fresh or frozen embryo transfer (FET) compared to spontaneous conceptions. METHODS: Cohort studies were identified from MEDLINE, Embase, Cochrane Library (January 2019), and manual search. Meta-analyses were performed to estimate odds ratios (OR) using random effects models in RevMan 5.3 and I-squared (I2) test > 50% was considered as high heterogeneity. RESULTS: After 3142 titles and abstracts were screened, 1180 full-text articles were assessed, and 14 were eligible. For fresh embryo transfer, the pooled ORs were PTB 1.64 (95% CI 1.46, 1.84); I2 = 97%; LBW 1.67 (95% CI 1.52, 1.85); I2 = 94%; SGA 1.46 [95% CI 1.11, 1.92]; I2 = 99%, LGA 0.88 (95% CI 0.80, 0.87); I2 = 80%). For frozen, the pooled ORs were PTB 1.39 (95% CI 1.34, 1.44); I2 = 0%; LBW 1.38 (95% CI 0.91, 2.09); I2 = 98%; SGA 0.83 (95% CI 0.57, 1.19); I2 = 0%, LGA 1.57 (95% CI 1.48, 1.68); I2 = 22%). CONCLUSIONS: When compared with spontaneous pregnancies, fresh, but not frozen was associated with LBW and SGA. Both fresh and frozen were associated with PTB. Frozen was uniquely associated with LGA. Despite improvements in ART protocols in relation to pregnancy rates, attention is needed towards monitoring adverse neonatal outcomes in these pregnancies.


Assuntos
Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Fertilização , Retardo do Crescimento Fetal/etiologia , Infertilidade/terapia , Nascimento Prematuro/etiologia , Técnicas de Reprodução Assistida , Estudos de Coortes , Criopreservação , Feminino , Retardo do Crescimento Fetal/epidemiologia , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Nascimento Prematuro/epidemiologia , Resultado do Tratamento
9.
Nutr Metab Cardiovasc Dis ; 30(6): 977-983, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32409273

RESUMO

BACKGROUND AND AIMS: Phenylketonuria (PKU)-affected women may become pregnant, and dietary phenylalanine (Phe) intake must be adjusted according to Phe tolerance. We report our experience with maternal PKU in relation to genotype PKU heterogeneity. METHODS AND RESULTS: A total of 10 pregnancies in 7 PKU women (7 different genotypes) were followed up as part of personalized care. Phe tolerance during preconception and pregnancy was assessed by strict dietary control and weekly Phe measurement (blood spots) in relation to genotype. Most women had stopped PKU diet during childhood or adolescence and six pregnancies were unplanned; a phenylalanine-restricted diet was reinstituted soon after conception. Women were classified according to their Phe levels at birth screening and genotype. Phe tolerance increased systematically in the course of pregnancy in all cases, but the increase was different in subjects with classic PKU (cPKU) when compared with cases with mild hyperphenylalaninemia (mHPA), both on average (+297 mg/day in cPKU vs. 597 in mHPA; P = 0.017) and as percentage (+107% in cPKU vs. +17% in mHPA). Notably, Phe tolerance also varied in the same women in the course of different pregnancies, when body weight gain was also different. Two newborns from the same cPKU mother (unplanned pregnancies on free diet) were affected by congenital alterations. CONCLUSIONS: Several factors influence metabolic phenotype in maternal PKU, to an unpredictable extent even in the same woman. The number of maternal PKU cases is growing in dedicated Nutrition Units, and the burden associated with careful management of this condition for the health care system should be adequately considered.


Assuntos
Dieta com Restrição de Proteínas , Fenilalanina Hidroxilase/genética , Fenilalanina/administração & dosagem , Fenilcetonúria Materna/dietoterapia , Adulto , Feminino , Retardo do Crescimento Fetal/etiologia , Predisposição Genética para Doença , Ganho de Peso na Gestação , Cardiopatias Congênitas/etiologia , Humanos , Nascimento Vivo , Fenótipo , Fenilalanina/efeitos adversos , Fenilalanina Hidroxilase/deficiência , Fenilcetonúria Materna/diagnóstico , Fenilcetonúria Materna/genética , Gravidez , Fatores de Risco , Rim Único/etiologia , Resultado do Tratamento , Adulto Jovem
10.
PLoS One ; 15(4): e0231028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298277

RESUMO

OBJECTIVE: Whether the use of assisted reproductive technologies (ART) affects the outcome of twin pregnancies is still a matter of debate. Previous studies have evaluated the association between birth weight and ART, without a clear distinction between fetal growth restriction (FGR), a condition at higher risk of adverse outcome, and constitutionally small for gestational age (SGA) fetuses. The aim of this study was to determine whether dichorionic (DC) twin pregnancies obtained by ART have a greater risk of developing FGR, defined by accurate ultrasound criteria, than those spontaneously conceived (SC), and to compare the severity of ultrasound features in the growth restricted fetuses. METHODS: A retrospective study was conducted on DC twin pregnancies delivered between 2010 to 2018 at a tertiary hospital. Twin pregnancies conceived spontaneously were compared with those obtained via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), after exclusion of cases with major fetal or uterine malformations. The primary outcome was the incidence of FGR. Secondary outcome was the rate of SGA neonates, defined by a birth weight less than the 10th percentile. The ultrasound characteristics of the growth restricted fetuses in the two groups were also compared. The groups were compared using univariate and multivariate analyses. RESULTS: Six hundred and seventy-eight DC twin pregnancies were identified. Of these, 367 (54.1%) conceived via IVF/ICSI and 311 (45.9%) conceived spontaneously. The incidence of FGR was not significantly different between the ART and the SC groups (7.9% vs 8.4% respectively, p = 0.76, adjusted OR 0.84, 95% CI 0.53-1.32). Growth restricted fetuses of the two groups showed similar occurrence of an estimated fetal weight less than the 3rd percentile, similar abnormalities in Doppler studies and similar gestational age at diagnosis. There was no difference in the incidence of delivery of an SGA neonate (p = 0.47) or in the rate of maternal complications and preterm delivery between the groups. CONCLUSIONS: Twin pregnancies conceived by assisted reproductive technologies do not have a higher risk of ultrasound-diagnosed FGR than spontaneously conceived twin pregnancies, and fetuses diagnosed with growth restriction in the two groups show similar severity of the ultrasound findings.


Assuntos
Retardo do Crescimento Fetal/etiologia , Gravidez de Gêmeos , Técnicas de Reprodução Assistida/efeitos adversos , Adulto , Feminino , Fertilização In Vitro/efeitos adversos , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/epidemiologia , Humanos , Incidência , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Resultado da Gravidez , Fatores de Risco , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Ultrassonografia Pré-Natal
11.
Arch Gynecol Obstet ; 301(5): 1189-1198, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32274638

RESUMO

PURPOSE: This cross-sectional case-control study of post-partum women aimed to estimate whether maternal periodontitis was a predictive contributor to preterm birth and to identify other risk factors associated with preterm birth in our target population. METHODS: The case group included women who delivered preterm (74 cases) and the control group included women who had a normal term delivery (120 controls). Medical records, a 16-item questionnaire, and a full-mouth periodontal examination were used to collect information about socio-demographic characteristics, general health problems, birth-related information, behavioral factors and periodontal status. Logistic regression analysis was used to estimate the strength of the relationship between predictors and the categorical outcome variable, preterm birth. RESULTS: The bivariate analysis revealed the significant associations between preterm birth and socio-demographic factors (educational level, p = 0.003), antepartum smoking habit (p = 0.001) and birth weight lower than 2500 g (p < 0.001). The multivariate analysis highlighted that the presence of post-partum maternal periodontitis and its severity remained independent risk factors of preterm birth in the presence of antepartum smoking habit and route of delivery [adjusted OR 2.26, 95% CI (1.06; 4.82), respectively, OR 3.46, 95% CI (1.08; 11.15)]. CONCLUSION: Post-partum maternal periodontal disease and its severity might, in part, be considered as contributor to preterm deliveries before 37 weeks of gestation.


Assuntos
Retardo do Crescimento Fetal/etiologia , Periodontite/complicações , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Fumar/efeitos adversos , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Estudos Transversais , Feminino , Hospitais , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Índice Periodontal , Periodontite/epidemiologia , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Resultado da Gravidez , Nascimento Prematuro/etiologia , Fatores de Risco , Romênia/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos
12.
Arch Gynecol Obstet ; 301(6): 1397-1404, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32333099

RESUMO

OBJECTIVE: In an attempt to shed new light on the pathogenesis of fetal growth restriction (FGR), we aimed to study pregnancy characteristics, neonatal outcomes, and placental histopathological lesions of FGR pregnancies in two different subgroups: when developed after appropriate for gestational age (AGA) pregnancy and when developed after previous pregnancy with FGR. STUDY DESIGN: Pregnancy and placental reports of all singleton pregnancies complicated by FGR (defined as actual birthweight below the 10th percentile according to local birthweight nomograms) between 2008 and 2018 were reviewed. Included were only cases with previous delivery. Maternal background, neonatal outcomes, and placental histopathology were compared between FGR that occurred after FGR (recurrent FGR group) and FGR that occurred after an AGA pregnancy (FGR after AGA group). Placental lesions were classified according to the current "Amsterdam" criteria. Continuous variables were compared using the Student's t test or the Mann-Whitney test as appropriate. Categorical variables were compared using Chi-square or Fisher's exact test as appropriate. RESULTS: A total of 334 FGR cases with a previous delivery were included in the study. Of them, 111 cases constituted the recurrent FGR group and 223 constituted the FGR after AGA group. The recurrent FGR group was characterized by higher rates of maternal diabetes during pregnancy and hypertensive diseases (9% versus 2.7%, p = 0.01 and 19.8% versus 11.6%, p = 0.04). The FGR after AGA group was characterized by a higher rate of fetal vascular malperfusion (FVM) lesions (29.6% versus 18.0%, p = 0.02), and by lower mean birthweight (1842 ± 424.9 versus 1977.4 ± 412.2, p = 0.005), as compared to the recurrent FGR group. CONCLUSION: Recurrent FGR was associated with maternal background morbidities during pregnancy which represents a chronic repeated insult, while "new" FGR cases (those followed an AGA pregnancy) were characterized by a higher rate of FVM lesions and lower birthweight which probably represent an "accident" in placentation. These findings may suggest that different mechanisms of placental dysfunction exist in the two subgroups of FGR.


Assuntos
Retardo do Crescimento Fetal/etiologia , Placenta/patologia , Adulto , Feminino , Retardo do Crescimento Fetal/patologia , Idade Gestacional , Humanos , Gravidez , Resultado da Gravidez , Recidiva
13.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R929-R939, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32130027

RESUMO

Women in low- and middle-income countries frequently consume a protein-deficient diet during pregnancy and breastfeeding. The effects of gestational malnutrition on fetal and early postnatal development can have lasting adverse effects on offspring metabolism. Expanding on previous studies in rodent models, we utilized a nonhuman primate model of gestational and early-life protein restriction (PR) to evaluate effects on the organ development and glucose metabolism of juvenile offspring. Offspring were born to dams that had consumed a control diet containing 26% protein or a PR diet containing 13% protein. Offspring were maintained on the PR diet and studied [body and serum measurements, intravenous glucose tolerance tests (ivGTTs), and dual-energy X-ray absorptiometry scans] up to 7 mo of age, at which time tissues were collected for analysis. PR offspring had age-appropriate body weight and were euglycemic but exhibited elevated fasting insulin and reduced initial, but increased total, insulin secretion during an ivGTT at 6 mo of age. No changes were detected in pancreatic islets of PR juveniles; however, PR did induce changes, including reduced kidney size, and changes in liver, adipose tissue, and muscle gene expression in other peripheral organs. Serum osteocalcin was elevated and bone mineral content and density were reduced in PR juveniles, indicating a significant impact of PR on early postnatal bone development.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Dieta com Restrição de Proteínas , Metabolismo Energético , Retardo do Crescimento Fetal/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Animais , Glicemia/metabolismo , Composição Corporal , Desenvolvimento Ósseo , Modelos Animais de Doenças , Metabolismo Energético/genética , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/fisiopatologia , Regulação da Expressão Gênica no Desenvolvimento , Resistência à Insulina , Macaca mulatta , Masculino , Estado Nutricional , Gravidez
14.
In Vivo ; 34(2): 649-657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111765

RESUMO

BACKGROUND/AIM: Intrauterine growth retardation (IUGR) causes very low birth weight and is related to the morbidity and mortality of the newborn. In our previous study, expression of brain-derived neurotrophic factor (BDNF) was found reduced in the cerebral cortex and dentate gyrus of fetuses with IUGR. BDNF protected cortical neurons against hypoxic injury via activation of the extracellular signal-related kinase (ERK) pathway. The aim of the current study was to observe the immunoreactivity of ERK in mature neurons and proliferating cells. MATERIALS AND METHODS: Uterine artery ligation was performed at 17 days of gestation (dg). Rat fetuses were obtained at 21 dg using cesarean section. Fetuses were designated either to the growth retardation (GR) group when removed from the horn with uterine artery ligation, or to the control group when removed from the other horn with the untied artery. Immunohistochemistry was performed with primary antibodies on paraffin-embedded forebrain sections. RESULTS: The density and proportion of cells expressing PCNA, ERK, and phosphate ERK in the subventricular zone (SVZ) was not different between the control and GR group. The density and proportion of NeuN- and phosphate ERK-positive cells in the cerebral parietal cortex was lower in the GR group, compared to the control group. CONCLUSION: Although IUGR had no effect on the proliferation of cells in the SVZ, it reduced neuronal survival in the cerebral parietal cortex, which was associated with the decrease of pERK-positive cell density and proportion in the cerebral cortex.


Assuntos
Modelos Animais de Doenças , Retardo do Crescimento Fetal/fisiopatologia , Sistema de Sinalização das MAP Quinases/fisiologia , Artéria Uterina/cirurgia , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Sobrevivência Celular , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/metabolismo , Imuno-Histoquímica , Ligadura/efeitos adversos , Neurônios/citologia , Neurônios/metabolismo , Fosforilação , Antígeno Nuclear de Célula em Proliferação/biossíntese , Ratos Sprague-Dawley
15.
Pregnancy Hypertens ; 20: 27-35, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32145525

RESUMO

OBJECTIVE: To determine the rate of sonographic placental markers and their predictive value for preeclampsia and fetal growth restriction in women with chronic kidney disease (CKD). STUDY DESIGN: A retrospective cohort study of women with CKD followed at a tertiary referral center between 2016 and 2019 (n = 86). All women underwent 2nd trimester sonographic placental examinations that included assessment of placental morphology, umbilical cord, and uterine artery Doppler. Continuous placental markers were converted to multiples on medians (MoM). MAIN OUTCOME MEASURES: Predictive value of sonographic markers for preeclampsia and birthweight < 10th percentile. RESULTS: Women in the cohort had a high rate of preeclampsia (24.4%), birthweight < 10th% (26.7%), and preterm birth (30.2%). The most important markers were placental volume and uterine artery Doppler: the risk of preeclampsia was elevated in women with low placental volume (51.7% vs. 10.9%; OR = 8.79 [2.70-28.59] for preeclampsia; and 40.0% vs. 9.1%; OR = 6.67 [1.85-24.04] for preterm preeclampsia), and in women with bilateral uterine artery notching (62.5% vs. 20.8%; OR = 6.35 [1.37-29.45] for preeclampsia; and 62.5% vs. 10.4%; OR = 14.38 [1.29-71.75] for preterm preeclampsia). The combination of both markers had the strongest predictive value for preeclampsia (positive likelihood ratio = 8.25 [6.84-9.95]). Low placental volume and bilateral uterine notching were also associated with birthweight < 10th percentile. CONCLUSION: A 2nd-trimester sonographic placental study can identify a subgroup of women with CKD who are at most risk of preeclampsia and fetal growth restriction. Such data may inform their subsequent perinatal care and assist care providers in the often challenging distinction between preeclampsia flare of underlying CKD.


Assuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Placenta/diagnóstico por imagem , Pré-Eclâmpsia/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Adulto , Peso ao Nascer , Feminino , Retardo do Crescimento Fetal/etiologia , Idade Gestacional , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Pré-Eclâmpsia/etiologia , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/etiologia , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Cordão Umbilical/diagnóstico por imagem , Artéria Uterina/diagnóstico por imagem
16.
Br J Nutr ; 124(4): 432-439, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32213215

RESUMO

Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted ß = -49·4 g, 95 % CI -91·1, -7·8, P < 0·05; for severe VDD: adjusted ß = -79·8 g, 95 % CI -127·2, -32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted ß = -44·5 g, 95 % CI -82·6, -6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted ß = -124·7 g, 95 % CI -194·6, -54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.


Assuntos
Retardo do Crescimento Fetal/epidemiologia , Hormônio Paratireóideo/sangue , Complicações na Gravidez/epidemiologia , Segundo Trimestre da Gravidez/sangue , Deficiência de Vitamina D/sangue , Adulto , Peso ao Nascer , China/epidemiologia , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/etiologia , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/etiologia , Estudos Prospectivos , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/complicações
17.
Obstet Gynecol Clin North Am ; 47(1): 163-181, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32008666

RESUMO

Preeclampsia may arise from impaired decidualization in some women. Transcriptomics of mid-secretory biopsy endometrial stromal cells decidualized in vitro and of early gestation choriodecidua from women who experienced preeclampsia with severe features overlapped significantly with the classical endometrial disorders giving rise to the concept of "endometrium spectrum disorders". That is, recurrent implantation failure and miscarriage, endometriosis, normotensive intrauterine growth restriction, preeclampsia and preterm birth may all lie on a continuum of decidual dysregulation, in which phenotypic expression is determined by the specific molecular pathway(s) disrupted and severity of disruption. Women conceiving by programmed IVF protocols showed widespread dysregulation of cardiovascular function and increased rates of adverse pregnancy outcomes including preeclampsia. Programmed cycles preclude development of a corpus luteum (CL), a major regulator of endometrial function. Lack of circulating CL product(s) that are not replaced in programmed cycles (eg, relaxin) could adversely impact the maternal cardiovascular system directly and/or compromise decidualization, thereby increasing preeclampsia risk.


Assuntos
Corpo Lúteo/diagnóstico por imagem , Endométrio/diagnóstico por imagem , Retardo do Crescimento Fetal/diagnóstico , Implantação do Embrião , Feminino , Retardo do Crescimento Fetal/etiologia , Humanos , Gravidez , Resultado da Gravidez
18.
Obstet Gynecol Clin North Am ; 47(1): 81-98, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32008673

RESUMO

Placental dysfunction is a major contributing factor to fetal growth restriction. Placenta-mediated fetal growth restriction occurs through chronic fetal hypoxia owing to poor placental perfusion through a variety of mechanisms. Maternal vascular malperfusion is the most common placental disease contributing to fetal growth restriction; however, the role of rare placental diseases should not be overlooked. Although the features of maternal vascular malperfusion are identifiable on placental pathology, antepartum diagnostic methods are evolving. Placental imaging and uterine artery Doppler, used in conjunction with angiogenic growth factors (specifically placenta growth factor and soluble fms-like tyrosine kinase-1), play an increasingly important role.


Assuntos
Retardo do Crescimento Fetal/etiologia , Placenta/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Recém-Nascido , Gravidez , Ultrassonografia Doppler/métodos
19.
Am J Physiol Lung Cell Mol Physiol ; 318(3): L549-L561, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31913647

RESUMO

Prenatal smoke exposure (PSE) is associated with reduced birth weight, impaired fetal development, and increased risk for diseases later in life. Changes in DNA methylation may be involved, as multiple large-scale epigenome-wide association studies showed that PSE is robustly associated with DNA methylation changes in blood among offspring in early life. Insulin-like growth factor-1 (IGF1) is important in growth, differentiation, and repair processes after injury. However, no studies investigated the organ-specific persistence of PSE-induced methylation change of Igf1 into adulthood. Based on our previous studies on the PSE effect on Igf1 promoter methylation in fetal and neonatal mouse offspring, we now have extended our studies to adulthood. Our data show that basal Igf1 promoter methylation generally increased in the lung but decreased in the liver (except for 2 persistent CpG sites in both organs) across three different developmental stages. PSE changed Igf1 promoter methylation in all three developmental stages, which was organ and sex specific. The PSE effect was less pronounced in adult offspring compared with the fetal and neonatal stages. In addition, the PSE effect in the adult stage was more pronounced in the lung compared with the liver. For most CpG sites, an inverse correlation was found for promoter methylation and mRNA expression when the data of all three stages were combined. This was more prominent in the liver. Our findings provide additional evidence for sex- and organ-dependent prenatal programming, which supports the developmental origins of health and disease (DOHaD) hypothesis.


Assuntos
Metilação de DNA , Retardo do Crescimento Fetal/patologia , Regulação da Expressão Gênica no Desenvolvimento , Fator de Crescimento Insulin-Like I/genética , Efeitos Tardios da Exposição Pré-Natal/patologia , Regiões Promotoras Genéticas , Fumaça/efeitos adversos , Animais , Animais Recém-Nascidos , Epigênese Genética , Feminino , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/metabolismo , Masculino , Camundongos , Especificidade de Órgãos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fatores Sexuais
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