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OBJECTIVES: Accurate assessment of gestational age (GA) is important at both individual and population levels. The most accurate way to estimate GA in women who book late in pregnancy is unknown. The aim of this study was to externally validate the accuracy of equations for GA estimation in late pregnancy and to identify the best equation for estimating GA in women who do not receive an ultrasound scan until the second or third trimester. DESIGN: This was a prospective, observational cross-sectional study. SETTING: 57 prenatal care centres, France. PARTICIPANTS: Women with a singleton pregnancy and a previous 11-14-week dating scan that gave the observed GA were recruited over an 8-week period. They underwent a standardised ultrasound examination at one time point during the pregnancy (15-43 weeks), measuring 12 foetal biometric parameters that have previously been identified as useful for GA estimation. MAIN OUTCOME MEASURES: A total of 189 equations that estimate GA based on foetal biometry were examined and compared with GA estimation based on foetal CRL. Comparisons between the observed GA and the estimated GA were made using R2, calibration slope and intercept. RMSE, mean difference and 95% range of error were also calculated. RESULTS: A total of 2741 pregnant women were examined. After exclusions, 2339 participants were included. In the 20 best performing equations, the intercept ranged from -0.22 to 0.30, the calibration slope from 0.96 to 1.03 and the RSME from 0.67 to 0.87. Overall, multiparameter models outperformed single-parameter models. Both the 95% range of error and mean difference increased with gestation. Commonly used models based on measurement of the head circumference alone were not amongst the best performing models and were associated with higher 95% error and mean difference. CONCLUSIONS: We provide strong evidence that GA-specific equations based on multiparameter models should be used to estimate GA in late pregnancy. However, as all methods of GA assessment in late pregnancy are associated with large prediction intervals, efforts to improve access to early antenatal ultrasound must remain a priority. TRIAL REGISTRATION: The proposal for this study and the corresponding methodological review was registered on PROSPERO international register of systematic reviews (registration number: CRD4201913776).
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INTRODUCTION: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR. METHODS AND ANALYSIS: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3. ETHICS AND DISSEMINATION: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies. TRIAL REGISTRATION NUMBER: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201).
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Estudos de Viabilidade , Retardo do Crescimento Fetal , Gravidez de Gêmeos , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Feminino , Gravidez , Retardo do Crescimento Fetal/terapia , Estudos Prospectivos , Gêmeos Monozigóticos , Conduta Expectante , Recém-NascidoRESUMO
Auditory and visual signals are two primary perception modalities that are usually present together and correlate with each other, not only in natural environments but also in clinical settings. However, audio-visual modelling in the latter case can be more challenging, due to the different sources of audio/video signals and the noise (both signal-level and semantic-level) in auditory signals-usually speech audio. In this study, we consider audio-visual modelling in a clinical setting, providing a solution to learn medical representations that benefit various clinical tasks, without relying on dense supervisory annotations from human experts for the model training. A simple yet effective multi-modal self-supervised learning framework is presented for this purpose. The proposed approach is able to help find standard anatomical planes, predict the focusing position of sonographer's eyes, and localise anatomical regions of interest during ultrasound imaging. Experimental analysis on a large-scale clinical multi-modal ultrasound video dataset show that the proposed novel representation learning method provides good transferable anatomical representations that boost the performance of automated downstream clinical tasks, even outperforming fully-supervised solutions. Being able to learn such medical representations in a self-supervised manner will contribute to several aspects including a better understanding of obstetric imaging, training new sonographers, more effective assistive tools for human experts, and enhancement of the clinical workflow.
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Ultrassonografia , Humanos , Ultrassonografia/métodos , Feminino , Percepção Visual/fisiologia , Gravação em VídeoRESUMO
OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.
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BACKGROUND: The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor is a useful biomarker for preeclampsia. Since it is a measure of placental dysfunction, it could also be a predictor of clinical deterioration and fetal tolerance to intrapartum stress. OBJECTIVE: We tested the hypothesis that soluble fms-like tyrosine kinase 1 to placental growth factor ratio predicts time to delivery. Secondary objectives were to examine associations between the soluble fms-like tyrosine kinase 1 to placental growth factor ratio and mode of birth, fetal distress, need for labor induction, and birthweight z score. STUDY DESIGN: Secondary analysis of the INSPIRE trial, a randomized interventional study on prediction of preeclampsia/eclampsia in which women with suspected preeclampsia were recruited and their blood soluble fms-like tyrosine kinase 1 to placental growth factor ratio was assessed. We stratified participants into 3 groups according to the ratio result: category 1 (soluble fms-like tyrosine kinase 1 to placental growth factor ≤38); category 2 (soluble fms-like tyrosine kinase 1 to placental growth factor >38 and <85); and category 3 (soluble fms-like tyrosine kinase 1 to placental growth factor ≥85). We modeled time from soluble fms-like tyrosine kinase 1 to placental growth factor determination to delivery using Kaplan-Meier curves and compared the 3 ratio categories adjusting for gestational age at soluble fms-like tyrosine kinase 1 to placental growth factor determination and trial arm with Cox regression. The association between ratio category and mode of delivery, induction of labor, and fetal distress was assessed using a multivariable logistic regression adjusting for gestational age at sampling and trial arm. The association between birthweight z score and soluble fms-like tyrosine kinase 1 to placental growth factor ratio was evaluated using multiple linear regression. Subgroup analysis was conducted in women with no preeclampsia and spontaneous onset of labor; women with preeclampsia; and participants in the nonreveal arm. RESULTS: Higher ratio categories were associated with a shorter latency from soluble fms-like tyrosine kinase 1 to placental growth factor determination to delivery (37 vs 13 vs 10 days for ratios categories 1-3 respectively), hazards ratio for category 3 ratio of 5.64 (95% confidence interval 4.06-7.84, P<.001). A soluble fms-like tyrosine kinase 1 to placental growth factor ratio ≥85 had specificity of 92.7% (95% confidence interval 89.0%-95.1%) and sensitivity of 54.72% (95% confidence interval, 41.3-69.5) for prediction of preeclampsia indicated delivery within 2 weeks. A ratio category 3 was also associated with decreased odds of spontaneous vaginal delivery (Odds ratio [OR] 0.47, 95% confidence interval 0.25-0.89); an almost 6-fold increased risk of emergency cesarean section (OR 5.89, 95% confidence interval 3.05-11.21); and a 2-fold increased risk for intrapartum fetal distress requiring operative delivery or cesarean section (OR 3.04, 95% confidence interval 1.53-6.05) when compared to patients with ratios ≤38. Higher ratio categories were also associated with higher odds of induction of labor when compared to ratios category 1 (category 2, OR 2.20, 95% confidence interval 1.02-4.76; category 3, OR 6.0, 95% confidence interval 2.01-17.93); and lower median birthweight z score. Within subgroups of women a) without preeclampsia and with spontaneous onset of labor and b) women with preeclampsia, the log ratio was significantly higher in patients requiring intervention for fetal distress or failure to progress compared to those who delivered vaginaly without intervention. In the subset of women with no preeclampsia and spontaneous onset of labor, those who required intervention for fetal distress or failure to progress had a significantly higher log ratio than those who delivered vaginaly without needing intervention. CONCLUSION: The soluble fms-like tyrosine kinase 1 to placental growth factor ratio might be helpful in risk stratification of patients who present with suspected preeclampsia regarding clinical deterioration, intrapartum fetal distress, and mode of birth (including the need for intervention in labor).
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OBJECTIVE: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. DESIGN: Superiority, double-blind randomised controlled trial. SETTING: A total of 20 UK fetal medicine units. POPULATION: Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. METHODS: Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. MAIN OUTCOME MEASURES: All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. RESULTS: In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). CONCLUSIONS: Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.
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Preterm birth (PTB) is a complex syndrome traditionally defined by a single parameter, namely, gestational age at birth (ie, Ë37 weeks). This approach has limitations for clinical usefulness and may explain the lack of progress in identifying cause-specific effective interventions. The authors offer a framework for a functional taxonomy of PTB based on (1) conceptual principles established a priori; (2) known etiologic factors; (3) specific, prospectively identified obstetric and neonatal clinical phenotypes; and (4) postnatal follow-up of growth and development up to 2 years of age. This taxonomy includes maternal, placental, and fetal conditions routinely recorded in data collection systems.
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Nascimento Prematuro , Humanos , Feminino , Gravidez , Recém-Nascido , Idade Gestacional , Recém-Nascido Prematuro , Síndrome , Fatores de Risco , Ruptura Prematura de Membranas FetaisRESUMO
OBJECTIVE: We present a statistical characterisation of fetal anatomies in obstetric ultrasound video sweeps where the transducer follows a fixed trajectory on the maternal abdomen. METHODS: Large-scale, frame-level manual annotations of fetal anatomies (head, spine, abdomen, pelvis, femur) were used to compute common frame-level anatomy detection patterns expected for breech, cephalic, and transverse fetal presentations, with respect to video sweep paths. The patterns, termed statistical heatmaps, quantify the expected anatomies seen in a simple obstetric ultrasound video sweep protocol. In this study, a total of 760 unique manual annotations from 365 unique pregnancies were used. RESULTS: We provide a qualitative interpretation of the heatmaps assessing the transducer sweep paths with respect to different fetal presentations and suggest ways in which the heatmaps can be applied in computational research (e.g., as a machine learning prior). CONCLUSION: The heatmap parameters are freely available to other researchers (https://github.com/agleed/calopus_statistical_heatmaps).
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Feto , Ultrassonografia Pré-Natal , Humanos , Ultrassonografia Pré-Natal/métodos , Feminino , Gravidez , Feto/diagnóstico por imagem , Feto/anatomia & histologia , Gravação em VídeoRESUMO
BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.
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Poluentes Atmosféricos , Desenvolvimento Fetal , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Biomassa , Culinária , Índia , Estados Unidos , Adolescente , Adulto Jovem , AdultoRESUMO
OBJECTIVE: Automated medical image analysis solutions should closely mimic complete human actions to be useful in clinical practice. However, more often an automated image analysis solution represents only part of a human task, which restricts its practical utility. In the case of ultrasound-based fetal biometry, an automated solution should ideally recognize key fetal structures in freehand video guidance, select a standard plane from a video stream and perform biometry. A complete automated solution should automate all three subactions. METHODS: In this article, we consider how to automate the complete human action of first-trimester biometry measurement from real-world freehand ultrasound. In the proposed hybrid convolutional neural network (CNN) architecture design, a classification regression-based guidance model detects and tracks fetal anatomical structures (using visual cues) in the ultrasound video. Several high-quality standard planes that contain the mid-sagittal view of the fetus are sampled at multiple time stamps (using a custom-designed confident-frame detector) based on the estimated probability values associated with predicted anatomical structures that define the biometry plane. Automated semantic segmentation is performed on the selected frames to extract fetal anatomical landmarks. A crown-rump length (CRL) estimate is calculated as the mean CRL from these multiple frames. RESULTS: Our fully automated method has a high correlation with clinical expert CRL measurement (Pearson's p = 0.92, R-squared [R2] = 0.84) and a low mean absolute error of 0.834 (weeks) for fetal age estimation on a test data set of 42 videos. CONCLUSION: A novel algorithm for standard plane detection employs a quality detection mechanism defined by clinical standards, ensuring precise biometric measurements.
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Biometria , Primeiro Trimestre da Gravidez , Ultrassonografia Pré-Natal , Humanos , Ultrassonografia Pré-Natal/métodos , Feminino , Gravidez , Biometria/métodos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Feto/diagnóstico por imagem , Feto/anatomia & histologiaRESUMO
Background: Knowledge of gestational age (GA) is key in clinical management of individual obstetric patients, and critical to be able to calculate rates of preterm birth and small for GA at a population level. Currently, the gold standard for pregnancy dating is measurement of the fetal crown rump length at 11-14 weeks of gestation. However, this is not possible for women first presenting in later pregnancy, or in settings where routine ultrasound is not available. A reliable, cheap and easy to measure GA-dependent biomarker would provide an important breakthrough in estimating the age of pregnancy. Therefore, the aim of this study was to determine the accuracy of prenatal and postnatal biomarkers for estimating gestational age (GA). Methods: Systematic review prospectively registered with PROSPERO (CRD42020167727) and reported in accordance with the PRISMA-DTA. Medline, Embase, CINAHL, LILACS, and other databases were searched from inception until September 2023 for cohort or cross-sectional studies that reported on the accuracy of prenatal and postnatal biomarkers for estimating GA. In addition, we searched Google Scholar and screened proceedings of relevant conferences and reference lists of identified studies and relevant reviews. There were no language or date restrictions. Pooled coefficients of correlation and root mean square error (RMSE, average deviation in weeks between the GA estimated by the biomarker and that estimated by the gold standard method) were calculated. The risk of bias in each included study was also assessed. Findings: Thirty-nine studies fulfilled the inclusion criteria: 20 studies (2,050 women) assessed prenatal biomarkers (placental hormones, metabolomic profiles, proteomics, cell-free RNA transcripts, and exon-level gene expression), and 19 (1,738,652 newborns) assessed postnatal biomarkers (metabolomic profiles, DNA methylation profiles, and fetal haematological components). Among the prenatal biomarkers assessed, human chorionic gonadotrophin measured in maternal serum between 4 and 9 weeks of gestation showed the highest correlation with the reference standard GA, with a pooled coefficient of correlation of 0.88. Among the postnatal biomarkers assessed, metabolomic profiling from newborn blood spots provided the most accurate estimate of GA, with a pooled RMSE of 1.03 weeks across all GAs. It performed best for term infants with a slightly reduced accuracy for preterm or small for GA infants. The pooled RMSEs for metabolomic profiling and DNA methylation profile from cord blood samples were 1.57 and 1.60 weeks, respectively. Interpretation: We identified no antenatal biomarkers that accurately predict GA over a wide window of pregnancy. Postnatally, metabolomic profiling from newborn blood spot provides an accurate estimate of GA, however, as this is known only after birth it is not useful to guide antenatal care. Further prenatal studies are needed to identify biomarkers that can be used in isolation, as part of a biomarker panel, or in combination with other clinical methods to narrow prediction intervals of GA estimation. Funding: The research was funded by the Bill and Melinda Gates Foundation (INV-000368). ATP is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre funding scheme. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, the Department of Health, or the Department of Biotechnology. The funders of this study had no role in study design, data collection, analysis or interpretation of the data, in writing the paper or the decision to submit for publication.
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BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).
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Poluição do Ar em Ambientes Fechados , Petróleo , Lactente , Feminino , Humanos , Gravidez , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Biomassa , Material Particulado/efeitos adversos , Material Particulado/análise , Culinária , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/prevenção & controleRESUMO
BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).
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Poluição do Ar em Ambientes Fechados , Biomassa , Culinária , Exposição por Inalação , Petróleo , Pneumonia , Feminino , Humanos , Lactente , Gravidez , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Culinária/métodos , Material Particulado/efeitos adversos , Material Particulado/análise , Petróleo/efeitos adversos , Pneumonia/etiologia , Adolescente , Adulto Jovem , Adulto , Internacionalidade , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/etiologiaRESUMO
Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to <35 years of age; gestation confirmed by ultrasound at 9 to <20 weeks) were randomly assigned to intervention or control arms. We monitored these fetal and neonatal outcomes and personal exposure to PM2.5, BC and CO three times during pregnancy, we conducted intention-to-treat (ITT) and exposure-response (E-R) analyses to determine if the HAPIN intervention and corresponding HAP exposure was associated with the risk of fetal/neonatal outcomes. A total of 3200 women (mean age 25.4 ± 4.4 years, mean gestational age at randomization 15.4 ± 3.1 weeks) were included in this analysis. Relative risks for stillbirth, congenital anomaly and neonatal mortality were 0.99 (0.60, 1.66), 0.92 (95 % CI 0.52, 1.61), and 0.99 (0.54, 1.85), respectively, among women in the intervention arm compared to controls in an ITT analysis. Higher mean personal exposures to PM2.5, CO and BC during pregnancy were associated with a higher, but statistically non-significant, incidence of adverse outcomes. The LPG stove and fuel intervention did not reduce the risk of these outcomes nor did we find evidence supporting an association between personal exposures to HAP and stillbirth, congenital anomalies and neonatal mortality.
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Poluição do Ar em Ambientes Fechados , Poluição do Ar , Petróleo , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Adulto Jovem , Poluição do Ar em Ambientes Fechados/análise , Culinária , Mortalidade Infantil , Material Particulado/análise , Petróleo/toxicidade , Fuligem , Natimorto/epidemiologia , AdolescenteRESUMO
BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.
Assuntos
Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Progesterona/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Hipertensão Induzida pela Gravidez/prevenção & controle , Nascimento Prematuro/prevenção & controleRESUMO
BACKGROUND AND OBJECTIVE: Over the past 2 years, several drugs have been approved for coronavirus disease 2019 (COVID-19) treatment, but their safety during pregnancy remains poorly understood. This study aims to assess the relative risk of obstetric, neonatal, and infant outcomes associated with the use of drugs specifically indicated for the treatment of COVID-19 compared with other drug treatment strategies. The purpose of this article is to present elements of the study protocol. METHODS: The COVID-19 International Drug Pregnancy Registry (COVID-PR) is a noninterventional, postmarketing cohort study. Pregnant women receiving treatment with monoclonal antibodies (mAbs) or antiviral drugs for mild, moderate, or severe COVID-19 are matched 1:1 with pregnant women not receiving these study-specific drugs, based on calendar time, country, gestational age at enrollment, and COVID-19 severity. Participants complete online questionnaires at enrollment, during pregnancy, and for 12 months after delivery of liveborn infants. The study began enrolling participants on 1 December 2021 and is set to span 5 years for each drug of interest. DISCUSSION: The COVID-PR is designed to evaluate the safety profile of each studied drug. Additionally, it may allow for an analysis of the effects of COVID-19 drug exposure during relevant gestational periods on specific neonatal outcomes. Although the sample size will be too small to detect associations with rare outcomes, the study has the potential to generate hypotheses for future research. Ultimately, these data can provide valuable insights for evidence-based decisions about COVID-19 treatment during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05013632. EU PAS EUPAS42517.
Assuntos
COVID-19 , Recém-Nascido , Humanos , Feminino , Gravidez , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Estudos de Coortes , Resultado do Tratamento , Sistema de RegistrosRESUMO
Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.
Assuntos
Encéfalo , Desenvolvimento Fetal , Feto , Pré-Escolar , Feminino , Humanos , Gravidez , Encéfalo/anatomia & histologia , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Feto/embriologia , Idade Gestacional , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/embriologia , Substância Cinzenta/crescimento & desenvolvimento , Voluntários Saudáveis , Internacionalidade , Imageamento por Ressonância Magnética , Tamanho do Órgão , Estudos Prospectivos , Organização Mundial da Saúde , Imageamento Tridimensional , UltrassonografiaRESUMO
In this work, we exploit multi-task learning to jointly predict the two decision-making processes of gaze movement and probe manipulation that an experienced sonographer would perform in routine obstetric scanning. A multimodal guidance framework, Multimodal-GuideNet, is proposed to detect the causal relationship between a real-world ultrasound video signal, synchronized gaze, and probe motion. The association between the multi-modality inputs is learned and shared through a modality-aware spatial graph that leverages useful cross-modal dependencies. By estimating the probability distribution of probe and gaze movements in real scans, the predicted guidance signals also allow inter- and intra-sonographer variations and avoid a fixed scanning path. We validate the new multi-modality approach on three types of obstetric scanning examinations, and the result consistently outperforms single-task learning under various guidance policies. To simulate sonographer's attention on multi-structure images, we also explore multi-step estimation in gaze guidance, and its visual results show that the prediction allows multiple gaze centers that are substantially aligned with underlying anatomical structures.
Assuntos
Atenção , Aprendizagem , Feminino , Gravidez , Humanos , Ultrassonografia Pré-Natal , UltrassonografiaRESUMO
In obstetric sonography, the quality of acquisition of ultrasound scan video is crucial for accurate (manual or automated) biometric measurement and fetal health assessment. However, the nature of fetal ultrasound involves free-hand probe manipulation and this can make it challenging to capture high-quality videos for fetal biometry, especially for the less-experienced sonographer. Manually checking the quality of acquired videos would be time-consuming, subjective and requires a comprehensive understanding of fetal anatomy. Thus, it would be advantageous to develop an automatic quality assessment method to support video standardization and improve diagnostic accuracy of video-based analysis. In this paper, we propose a general and purely data-driven video-based quality assessment framework which directly learns a distinguishable feature representation from high-quality ultrasound videos alone, without anatomical annotations. Our solution effectively utilizes both spatial and temporal information of ultrasound videos. The spatio-temporal representation is learned by a bi-directional reconstruction between the video space and the feature space, enhanced by a key-query memory module proposed in the feature space. To further improve performance, two additional modalities are introduced in training which are the sonographer gaze and optical flow derived from the video. Two different clinical quality assessment tasks in fetal ultrasound are considered in our experiments, i.e., measurement of the fetal head circumference and cerebellar diameter; in both of these, low-quality videos are detected by the large reconstruction error in the feature space. Extensive experimental evaluation demonstrates the merits of our approach.