Pulmonary vascular reactivity in growth restricted fetuses using computational modelling and machine learning analysis of fetal Doppler waveforms.

The aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24-37 weeks of gestation and data were acquired before and after oxygen administration. After, Machine Learning (ML) and a computational model were used on the Doppler waveforms to classify individuals and estimate pulmonary vascular resistance (PVR). Our results showed lower mean velocity time integral (VTI) in the main pulmonary and intrapulmonary arteries in baseline conditions in FGR individuals. Delta changes of the main pulmonary artery VTI and intrapulmonary artery pulsatility index before and after hyperoxygenation were significantly greater in FGR when compared with controls. Also, ML identified two clusters: A (including 66% controls and 34% FGR) with similar Doppler traces over time and B (including 33% controls and 67% FGR) with changes after hyperoxygenation. The computational model estimated the ratio of PVR before and after maternal hyperoxygenation which was closer to 1 in cluster A (cluster A 0.98 ± 0.33 vs cluster B 0.78 ± 0.28, p = 0.0156). Doppler ultrasound allows the detection of significant changes in pulmonary vasculature in most FGR at baseline, and distinct responses to hyperoxygenation. Future studies are warranted to assess its potential applicability in the clinical management of FGR.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Assessment of the cerebroplacental ratio and uterine arteries in low-risk pregnancies in early labour for the prediction of obstetric and neonatal outcomes.

BACKGROUND: The evidence-based management of human labor includes the antepartum identification of patients at risk for intrapartum hypoxia. However, available evidence has shown that most of the hypoxic-related complications occur among pregnancies classified at low-risk for intrapartum hypoxia, thus suggesting that the current strategy to identify the pregnancies at risk for intrapartum fetal hypoxia has limited accuracy. OBJECTIVE: To evaluate the role of the combined assessment of the cerebroplacental ratio (CPR) and uterine arteries (UtA) Doppler in the prediction of obstetric intervention (OI) for suspected intrapartum fetal compromise (IFC) within a cohort of low-risk singleton term pregnancies in early labor. METHODS: Prospective multicentre observational study conducted across four tertiary Maternity Units between January 2016 and September 2019. Low-risk term pregnancies with spontaneous onset of labor were included. A two-step multivariable model was developed to assess the risk of OI for suspected IFC. The baseline model included antenatal and intrapartum characteristics, while the combined model included antenatal and intrapartum characteristics plus Doppler anomalies such as CPR MoM < 10th percentile and mean UtA Doppler PI MoM ≥ 95th percentile. Predictive performance was determined by receiver-operating characteristics curve analysis. RESULTS: 804 women were included. At logistic regression analysis, CPR MoM < 10th percentile (aOR 1.269, 95 % CI 1.188-1.356, P < 0.001), mean UtA PI MoM ≥ 95th percentile (aOR 1.012, 95 % CI 1.001-1.022, P = 0.04) were independently associated with OI for suspected IFC. At ROC curve analysis, the combined model including antenatal characteristics plus abnormal CPR and mean UtA PI yielded an AUC of 0.78, 95 %CI(0.71-0.85), p < 0.001, which was significantly higher than the baseline model (AUC 0.61, 95 %CI(0.54-0.69), p = 0.007) (p < 0.001). The combined model was associated with a 0.78 (95 % CI 0.67-0.89) sensitivity, 0.68 (95 % CI 0.65-0.72) specificity, 0.15 (95 % CI 0.11-0.19) PPV, and 0.98 (0.96-0.99) NPV, 2.48 (95 % CI 2.07-2.97) LR + and 0.32 (95 % CI 0.19-0.53) LR- for OI due to suspected IFC. CONCLUSIONS: A predictive model including antenatal and intrapartum characteristics combined with abnormal CPR and mean UtA PI has a good capacity to rule out and a moderate capacity to rule in OI due to IFC, albeit with poor predictive value.

Pregnancies through oocyte donation. A mini review of pathways involved in placental dysfunction.

Pregnancies resulting from assisted reproductive techniques (ART) are increasingly prevalent worldwide. While most pregnancies conceived through in-vitro fertilization (IVF) progress without complications, mounting evidence suggests that these pregnancies are at a heightened risk of adverse perinatal outcomes. Specifically, IVF pregnancies involving oocyte donation have garnered attention due to numerous reports indicating an elevated risk profile for pregnancy-related complications within this subgroup of patients. The precise mechanisms contributing to this increased risk of complications remain incompletely understood. Nonetheless, it is likely that they are mediated by an abnormal immune response at the fetal-maternal interface. Additionally, these outcomes may be influenced by baseline patient characteristics, such as the etiology of infertility, absence of corpus luteum, and variations in endometrial preparation protocols, among other factors. This review aims to succinctly summarize the most widely accepted mechanisms that potentially contribute to the onset of placental dysfunction in pregnancies conceived through oocyte donation.

Routine third-trimester ultrasound assessment for intrauterine growth restriction.

Intrauterine growth restriction significantly impacts perinatal outcomes. Undetected IUGR escalates the risk of adverse outcomes. Serial symphysis-fundal height measurement, a recommended strategy, is insufficient in detecting abnormal fetal growth. Routine third-trimester ultrasounds significantly improve detection rates compared with this approach, but direct high-quality evidence supporting enhanced perinatal outcomes from routine scanning is lacking. In assessing fetal growth, abdominal circumference alone performs comparably to estimated fetal weight. Hadlock formulas demonstrate accurate fetal weight estimation across diverse gestational ages and settings. When choosing growth charts, prescriptive standards (encompassing healthy pregnancies) should be prioritized over descriptive ones. Customized fetal standards may enhance antenatal IUGR detection, but conclusive high-quality evidence is elusive. Emerging observational data suggest that longitudinal fetal growth assessment could predict adverse outcomes better. However, direct randomized trial evidence supporting this remains insufficient.

Term planned delivery based on fetal growth assessment with or without the cerebroplacental ratio in low-risk pregnancies (RATIO37): an international, multicentre, open-label, randomised controlled trial.

BACKGROUND: The cerebroplacental ratio is associated with perinatal mortality and morbidity, but it is unknown whether routine measurement improves pregnancy outcomes. We aimed to evaluate whether the addition of cerebroplacental ratio measurement to the standard ultrasound growth assessment near term reduces perinatal mortality and severe neonatal morbidity, compared with growth assessment alone. METHODS: RATIO37 was a randomised, open-label, multicentre, pragmatic trial, conducted in low-risk pregnant women, recruited from nine hospitals over six countries. The eligibility criteria were designed to be broad; participants were required to be 18 years or older, with an ultrasound-dated confirmed singleton pregnancy in the first trimester, an alive fetus with no congenital malformations at the routine second-trimester ultrasound, an absence of adverse medical or obstetric history, and the capacity to give informed consent. Women were randomly assigned in a 1:1 ratio (block size 100) using a web-based system to either the concealed group or revealed group. In the revealed group, the cerebroplacental ratio value was known by clinicians, and if below the fifth centile, a planned delivery after 37 weeks was recommended. In the concealed group, women and clinicians were blinded to the cerebroplacental ratio value. All participants underwent ultrasound at 36 + 0 to 37 + 6 weeks of gestation with growth assessment and Doppler evaluation. In both groups, planned delivery was recommended when the estimated fetal weight was below the tenth centile. The primary outcome was perinatal mortality from 24 weeks' gestation to infant discharge. The study is registered at ClinicalTrials.gov (NCT02907242) and is now closed. FINDINGS: Between July 29, 2016, and Aug 3, 2021, we enrolled 11 214 women, of whom 9492 (84·6%) completed the trial and were eligible for analysis (4774 in the concealed group and 4718 in the revealed group). Perinatal mortality occurred in 13 (0·3%) of 4774 pregnancies in the concealed group and 13 (0·3%) of 4718 in the revealed group (OR 1·45 [95% CI 0·76-2·76]; p=0·262). Overall, severe neonatal morbidity occurred in 35 (0·73%) newborns in the concealed group and 18 (0·38%) in the revealed group (OR 0·58 [95% CI 0·40-0·83]; p=0·003). Severe neurological morbidity occurred in 13 (0·27%) newborns in the concealed group and nine (0·19%) in the revealed group (OR 0·56 [95% CI 0·25-1·24]; p=0·153). Severe non-neurological morbidity occurred in 23 (0·48%) newborns in the concealed group and nine (0·19%) in the revealed group (0·58 [95% CI 0·39-0·87]; p=0·009). Maternal adverse events were not collected. INTERPRETATION: Planned delivery at term based on ultrasound fetal growth assessment and cerebroplacental ratio at term was not followed by a reduction of perinatal mortality although significantly reduced severe neonatal morbidity compared with fetal growth assessment alone. FUNDING: La Caixa foundation, Cerebra Foundation for the Brain Injured Child, Agència per la Gestió d'Ajuts Universitaris i de Recerca, and Instituto de Salud Carlos III.

Perinatal outcomes in 6640 singleton pregnancies after donor oocyte IVF across three continents over 7 years.

PURPOSE: Are trends in singleton donor oocyte IVF perinatal outcomes consistent over time among four international ethnically diverse infertility centers? METHODS: This retrospective cohort consisted of an infertility network of four international IVF centers across three continents. Singleton live births resulting from fresh and frozen donor oocyte embryo transfers from January 1, 2012 to December 31, 2018 were included. The main outcome measures were birth weight (BW), preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA) and gestational age (GA) at delivery. RESULTS: The entire cohort (n = 6640) consisted of 4753 fresh and 1887 frozen donor oocyte embryo transfers. Maternal age, parity, body mass index, neonatal sex and GA at delivery were similar for fresh and frozen donor oocyte embryo transfers in the entire cohort and within each infertility center. All four centers had a trend of decreased BW and rates of PTB before 32 weeks annually, although significance was not reached. Three of the four centers had annual increased trends of PTB before 37 weeks and LGA newborns, although significance was not reached. BWs for the entire cohort for fresh and frozen donor embryo transfers were 3166 g ± 601 g and 3137 g ± 626 g, respectively. CONCLUSION: Similar trends in perinatal outcomes were present across four international infertility centers over 7 years. The overall perinatal trends in donor oocyte IVF may be applicable to centers worldwide, but further studies in more geographic regions are needed.

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.

Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction.

BACKGROUNDSevere, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, thus preventing accurate patient counseling. We investigated the use of maternal serum protein and ultrasound measurements at diagnosis to predict fetal or neonatal death and 3 secondary outcomes: fetal death or delivery at or before 28+0 weeks, development of abnormal umbilical artery (UmA) Doppler velocimetry, and slow fetal growth.METHODSWomen with singleton pregnancies (n = 142, estimated fetal weights [EFWs] below the third centile, less than 600 g, 20+0 to 26+6 weeks of gestation, no known chromosomal, genetic, or major structural abnormalities) were recruited from 4 European centers. Maternal serum from the discovery set (n = 63) was analyzed for 7 proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease, and 5 proteins identified through pooled liquid chromatography and tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n = 60), with final models calculated from combined data.RESULTSThe most discriminative model for fetal or neonatal death included the EFW z score (Hadlock 3 formula/Marsal chart), gestational age, and UmA Doppler category (AUC, 0.91; 95% CI, 0.86-0.97) but was less well calibrated than the model containing only the EFW z score (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery at or before 28+0 weeks included maternal serum placental growth factor (PlGF) concentration and UmA Doppler category (AUC, 0.89; 95% CI, 0.83-0.94).CONCLUSIONUltrasound measurements and maternal serum PlGF concentration at diagnosis of severe, early-onset FGR predicted pregnancy outcomes of importance to patients and clinicians.TRIAL REGISTRATIONClinicalTrials.gov NCT02097667.FUNDINGThe European Union, Rosetrees Trust, Mitchell Charitable Trust.

Perinatal outcomes in 13,626 singleton pregnancies after autologous IVF across three continents over 7 years.

PURPOSE: Are trends in singleton autologous IVF perinatal outcomes consistent over time among five international infertility centers? METHODS: This was a retrospective cohort study from January 1, 2012, to December 31, 2018. This study was performed through a large infertility network at five international infertility centers in which patients who had a singleton live birth resulting from fresh and frozen autologous IVF cycles were included. The primary outcome was live birth weight (BW) with secondary outcomes of preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA), and gestational age at delivery. RESULTS: The entire cohort (n = 13,626) consisted of 6941 fresh and 6685 frozen autologous IVF cycles leading to singleton deliveries. Maternal age, parity, body mass index, neonatal sex, and GA at delivery were similar for fresh and frozen IVF cycles in the entire cohort and within each infertility center. Four centers had a trend of decreased BW and three centers had decreased rates of PTB before 32 and 28 weeks and LGA newborns annually, although significance was not reached. Three IVF centers had annual increased trends of PTB before 37 weeks and four centers had increased rates of SGA newborns, although significance was not reached. CONCLUSION: Similar trends in perinatal outcomes were present across five international infertility centers over 7 years. Additional studies are crucial to further assess and optimize perinatal outcomes at an international level.

Fetal Growth Velocity according to the Mode of Assisted Conception.

INTRODUCTION: Pregnancies conceived through assisted reproductive techniques (ARTs) are on the rise worldwide and have been associated with a higher risk of placental-related disease in the third trimester. METHODS: A cohort was created of singleton pregnancies after assisted reproduction, admitted at our institution for delivery, between January 2020 and August 2022. Fetal growth velocity from the second trimester to delivery was compared against a gestational-age-matched group of pregnancies spontaneously conceived according to the origin of the selected oocyte (i.e., autologous vs. donated). RESULTS: 125 singleton pregnancies conceived through ART were compared to 315 singleton spontaneous conceptions. Overall, after adjusting for possible confounders, multivariate analysis demonstrated that ART pregnancies had a significantly lower estimated fetal weight (EFW) z-velocity from the second trimester to delivery (adjusted mean difference = -0.002; p = 0.035) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 2.32 [95% CI, 1.15-4.68]). Also, when ART pregnancies were compared according to the type of oocyte, those conceived with donated oocytes showed a significantly lower EFW z-velocity from the second trimester to delivery (adjusted mean difference = -0.008; p = 0.001) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 5.33 [95% CI, 1.34-21.5]). CONCLUSIONS: Pregnancies achieved through ART exhibit a pattern of lower growth velocity across the third trimester, especially those conceived with donated oocytes. The former represents a sub-group at the highest risk of placental dysfunction that may warrant closer follow-up.

Correlation of placental lesions in patients with systemic lupus erythematosus, antiphospholipid syndrome and non-criteria obstetric antiphospholipid syndrome and adverse perinatal outcomes.

INTRODUCTION: We aimed to describe the pattern of placental injuries in women with systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS) and non-criteria obstetric APS (NC-OAPS), and to correlate the placental findings with the occurrence of adverse perinatal outcomes. METHODS: The perinatal outcomes and placental findings of pregnancies of women with SLE, APS, and NC-OAPS and gestational-age matched healthy controls were analyzed and classified according to the 2015 Redline - Classification of placental lesions. RESULTS: 91 women with SLE, APS, and NC-OAPS and 91 controls were included. Mean values of placental weight differed between groups, being significantly lower in NC-OAPS and APS groups compared to controls. Furthermore, 14.3% of placentas in the APS group were under the 3rd percentile, which was significantly higher in comparison with other groups. Regarding histopathological placental findings, maternal-side malperfusion was significantly increased in APS (46.4%) compared to NC-OAPS (14.3%) and SLE (9.5%). Fetal-side maldevelopment was significantly increased in NC-OAPS (19.1%) compared to controls (1.1%) and SLE (2.4%). A significantly increased prevalence of adverse perinatal outcomes (APOs) was observed in all studied groups compared to healthy controls (controls 3.3%, SLE 52.4%, NC-OAPS 57.1%, APS 64.3%). Overall, both maternal (OR 6.8, 95%CI 2.1-22) and fetal-side (OR 4.1, 95%CI 1.3-13.5) lesions were significantly associated with APO. Maternal malperfusion and fetal maldevelopment were the lesions most strongly associated with APOs. DISCUSSION: Pregnant women with SLE, APS, or NC-OAPS showed a different pattern of histopathological findings. Compared to controls, SLE, APS, and NC-OAPS conferred an increased risk of APOs that was strongly associated with placental maternal-side malperfusion and fetal-side maldevelopment.

Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features.

BACKGROUND: Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome. OBJECTIVE: To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia. STUDY DESIGN: This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34 week's gestation) severe preeclampsia. RESULTS: 63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]). CONCLUSIONS: The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.

Third-trimester uterine artery Doppler for prediction of adverse outcome in late small-and adequate for-gestational-age fetuses.

Fetal growth restriction includes all those fetuses that do not reach their own growth potential due to placental insufficiency and therefore at higher risk of adverse perinatal outcomes. Identification and follow-up of these fetuses is essential to decrease this additional risk. Although estimated fetal weight under the 3rd centile and pathological cerebroplacental ratio are the most accepted predictive criteria, some evidence suggests that abnormal uterine artery Doppler may be a useful prognostic parameter in late-onset growth restriction fetuses at the moment of diagnosis. However, its prediction capacity as a standalone parameter is limited. In that context, integrated models of biometric and hemodynamic ultrasound parameters including uterine Doppler have been proposed as an effective approach to stratify the risk and improve perinatal outcomes. Moreover, an association of abnormal uterine artery Doppler and histological findings of placental underperfusion due to vascular obstruction has been described. Finally, it has also been suggested that the evaluation of uterine artery Doppler at third trimester in appropriate-for-gestational-age fetuses could identify cases of subclinical placental insufficiency, but further evidence is needed to define such predictive strategies.

Longitudinal change in cerebro-placental ratio (CPR) between 37 and 40 weeks of pregnancy is associated with non-reassuring fetal status and increased risk of cesarean section.

OBJECTIVE: To evaluate in low-risk pregnancies if longitudinal change in cerebro-placental ratio (CPR) between 37 and 40 weeks of pregnancy is associated with cesarean section (CS) for non-reassuring fetal status (NRFS) during labor. METHODS: This is a prospective observational study of women with singleton low-risk pregnancies who underwent an ultrasound scan at 36 + 0 to 37 + 6 and 39 + 0 to 41 + 6 weeks of pregnancy, when the CPR was calculated from the middle cerebral artery (MCA) and umbilical artery (UA) pulsatility indices. Managing professionals were kept blinded to the Doppler results. The association of the longitudinal change between both CPR (z-velocity) to CS for NRFS was evaluated by logistic regression. RESULTS: A total of 401 pregnancies were included. The mean time interval between both CPR evaluations was 21 days (SD 7). A CS for fetal distress was performed in 7% of pregnancies. Independent of the CPR at 37 weeks, the likelihood of CS for fetal distress was significantly decreased by the longitudinal changes from 37 to 40 weeks (OR 0.61, 95%CI 0.4-0.92; p=.018). This association remained significant after further adjustment for potential confounders (nulliparity, maternal weight at booking and estimated fetal weight at 37): (OR 0.64, 95%CI 0.41-0.98; p=.044). CONCLUSIONS: The longitudinal change of CPR between 37 and 40 weeks is associated with the need for CS for NRFS during labor.

Performance of the INTERGROWTH-21st and World Health Organization fetal growth charts for the detection of small-for-gestational age neonates in Latin America.

OBJECTIVE: To evaluate the performance of INTERGROWTH-21st (IG-21st ) and World Health Organization (WHO) fetal growth charts to identify small-for-gestational-age (SGA) and fetal growth restriction (FGR) neonates, as well as their specific risks for adverse neonatal outcomes. METHODS: Multicenter cross-sectional study including 67 968 live births from 10 maternity units across four Latin American countries. According to each standard, neonates were classified as SGA and FGR (birth weight <10th and less than third centiles, respectively). The relative risk (RR) and diagnostic performance for a low APGAR score and low ponderal index were calculated for each standard. RESULTS: WHO charts identified more neonates as SGA than IG-21st (13.9% vs 7%, respectively). Neonates classified as having FGR by both standards had the highest RR for a low APGAR (RR, 5.57 [95% confidence interval (CI), 3.99-7.78]), followed by those who were SGA by both curves (RR, 3.27 [95% CI, 2.52-4.24]), while neonates with SGA identified by WHO alone did not have an additional risk (RR, 0.87 [95% CI, 0.55-1.39]). Furthermore, the diagnostic odds ratio for a low APGAR was higher when IG-21st was used. CONCLUSION: In a population from Latin America, the WHO charts seem to identify more SGA neonates, but the diagnostic performance of the IG-21st charts for low APGAR score and low ponderal index is better.

Low-dose aspirin use in the first trimester of pregnancy and odds of congenital anomalies: A meta-analysis of randomized controlled trials.

BACKGROUND: Daily low-dose aspirin (LDA) is recommended in high-risk pregnancies. However, its safety profile in the first trimester has not been well documented. OBJECTIVES: To determine if LDA exposure during the first trimester of pregnancy is associated with higher odds of congenital structural anomalies. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were systematically searched. SELECTION CRITERIA: Randomized controlled trials (RCTs) that assigned participants to LDA (≤150 mg) or placebo/no intervention at less than 14 weeks of pregnancy were eligible. DATA COLLECTION AND ANALYSIS: Random-effects models were performed using the inverse-variance method to calculate pooled effect sizes. Quality of evidence was appraised according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. MAIN RESULTS: Eight RCTs that included 7564 participants assigned to receive daily LDA and 7670 participants that served as controls were analyzed. Low-certainty evidence showed no significant difference in the odds of congenital anomalies (odds ratio 0.87, 95% confidence interval 0.62-1.23, I2  = 0%). CONCLUSIONS: In this meta-analysis, there is no evidence to suggest safety concerns regarding LDA teratogenicity. However, given the overall low quality of evidence, further research (e.g. individual participant data meta-analysis) is needed to confirm LDA safety profile.

Death and severe morbidity in isolated periviable small-for-gestational-age fetuses.

OBJECTIVE: This study aims to predict perinatal death or severe sequelae in isolated small-for-gestational-age fetuses, diagnosed at a periviable gestational age, based on ultrasound and Doppler parameters at diagnosis. DESIGN: Observational study. SETTING: A tertiary perinatal centre. POPULATION: A cohort of singleton non-malformed fetuses suspected to be small for gestational age (estimated fetal weight, EFW, <10th centile) diagnosed at 22.0-25.6 weeks of gestation. The following parameters were recorded at diagnosis: severe smallness (<3rd centile); absent or reversed end-diastolic velocity in umbilical artery; abnormal middle cerebral artery Doppler; abnormal cerebroplacental ratio; abnormal uterine artery Doppler; and absent or reversed end-diastolic velocity in the ductus venosus. METHODS: Logistic regression analysis. MAIN OUTCOME MEASURES: Predictive performance of EFW and Doppler parameters for short-term adverse outcome of perinatal morbimortality and composite serious adverse outcomes (death, neurological impairment or severe bronchopulmonary dysplasia). RESULTS: A total of 155 pregnancies were included. There were 13 (8.4%) intrauterine and 11 (7.7%) neonatal deaths. A short-term adverse perinatal outcome occurred in 40 (25.8%) pregnancies. There were 31 (20%) cases of serious adverse outcomes. For the prediction of serious adverse outcomes, the combination of absent or reversed end-diastolic velocity in the umbilical artery and impaired middle cerebral artery detected by Doppler evaluation achieved a detection rate of 87%, with a false-positive rate of 14% (accuracy 86%). CONCLUSION: In periviable isolated small-for-gestational-age fetuses, a Doppler evaluation of the umbilical and fetal brain circulation can accurately predict short-term adverse perinatal complications and serious adverse outcomes.

Early Prediction of Adverse Pregnancy Outcome in Women with Systemic Lupus Erythematosus, Antiphospholipid Syndrome, or Non-Criteria Obstetric Antiphospholipid Syndrome.

A prospectively study of pregnant women with systemic lupus erythematosus (SLE), antiphospholipid syndrome, or non-criteria obstetric antiphospholipid syndrome was conducted to describe the characteristics of women followed in a referral unit and to derive a predictive tool for adverse pregnancy outcome (APO). Demographic characteristics, treatments, SLE activity, and flares were recorded. Laboratory data included a complete blood cell count, protein-to-creatinine urinary ratio (Pr/Cr ratio), complement, anti dsDNA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies status. A stepwise regression was used to identify baseline characteristics available before pregnancy and during the 1st trimester that were most predictive of APO and to create the predictive model. A total of 217 pregnancies were included. One or more APO occurred in 45 (20.7%) women. A baseline model including non-Caucasian ethnicity (OR 2.78; 95% CI [1.16-6.62]), smoking (OR 4.43; 95% CI [1.74-11.29]), pregestational hypertension (OR 16.13; 95% CI [4.06-64.02]), and pregestational corticosteroids treatment OR 2.98; 95% CI [1.30-6.87]) yielded an AUC of 0.78 (95% CI, [0.70-0.86]). Among first-trimester parameters, only Pr/Cr ratio improved the model fit, but the predictive performance was not significantly improved (AUC of 0.78 vs. 0.81; p = 0.16). Better biomarkers need to be developed to efficiently stratify pregnant women with the most common autoimmune diseases.