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Small fetuses are defined as those with an ultrasound estimated weight below a threshold, most commonly the 10th centile. The first clinically relevant step is the distinction of ‘true' fetal growth restriction (FGR), associated with signs of abnormal fetoplacental function and poorer perinatal outcome, from constitutional small-for-gestational age, with a near-normal perinatal outcome. Nowadays such a distinction should not be based solely on umbilical artery Doppler, since this index detects only early-onset severe forms. FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile, and, possibly in the near future, maternal angiogenic factors. Once the diagnosis is established, differentiating into early- and late-onset FGR is useful mainly for research purposes, because it distinguishes two clear phenotypes with differences in severity, association with preeclampsia, and the natural history of fetal deterioration. As a second clinically relevant step, management of FGR and the decision to deliver aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration and establishes follow-up intervals and optimal delivery timings, which may facilitate decisions and reduce practice variability in this complex clinical condition.

Maternal mental health is crucial for the well-being of both the mother and the fetus. Obstetric complications have been linked to anxiety and depression during pregnancy. Among them, preeclampsia (PE) and preterm premature rupture of membranes (PPROM), are the more common causes of maternal admission. The aim of this study is to explore whether there is an increasing prevalence in the gradient of anxiety and depression among women with uncomplicated pregnancies, those admitted for PPROM, and those admitted for PE. A cross-sectional t study was conducted involving three groups of pregnant women consecutively attended: 1) women admitted with severe PE; 2) women admitted with PPROM; and 3) uncomplicated pregnancies. Participants completed validated questionnaires to measure anxiety (State-Trait Anxiety Inventory, STAI), depression (Edinburgh Postnatal Depression Scale, EPDS). Differences in median scores across the study groups were analysed by quantile regression, adjusted for gestational age at evaluation and the STAI-Trait score. The analysis included 214 women: 106 with uncomplicated pregnancies, 55 with PPROM, and 53 with severe PE. A higher proportion of nulliparity and chronic hypertension was observed in women with preeclampsia. Significant trends across the study groups were observed for both depression and anxiety scores. Women with severe preeclampsia had higher scores on the State-Trait Anxiety Inventory-State (STAI-S) compared to those with PPROM (27 vs. 24; p=0.049). The PPROM and PE groups showed significantly higher proportions of abnormal scores in STAI-S>30, EPDS>10, and EPDS>13 compared to uncomplicated pregnancies. Higher levels of anxiety and depression are present in women admitted in hospital for PPROM and severe PE. Compared to PPROM, severe PE is associated with higher scores of anxiety. The importance of screening and offering specific interventions for patients with PE is highlighted.

Background: Green spaces are reported to improve health status, including beneficial effects on pregnancy outcomes. Despite the suggestions of air pollution-related health benefits of green spaces, there is no available evidence on the impact of greenness on personal exposure to air pollution. Objectives: We investigated the association between surrounding greenness and personal exposure to air pollution among pregnant women and to explore the potential mechanisms, if any, behind this association. Methods: In total, 65 rounds of sampling were carried out for 54 pregnant women who resided in Barcelona during 2008-2009. Each round consisted of a 2-day measurement of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM₂.₅) and a 1-week measurement of nitric oxides collected simultaneously at both the personal and microenvironmental levels. The study participants were also asked to fill out a time-microenvironment-activity diary during the sampling period. We used satellite retrievals to determine the surrounding greenness as the average of Normalized Difference Vegetation Index (NDVI) in a buffer of 100 m around each maternal residential address. We estimated the impact of surrounding greenness on personal exposure levels, home-outdoor and homeindoor pollutant levels, and maternal time-activity. Results: Higher residential surrounding greenness was associated with lower personal, homeindoor, and home-outdoor PM₂.₅ levels, and more time spent at home-outdoor. Conclusions: We found lower levels of personal exposure to air pollution among pregnant women residing in greener areas. This finding may be partly explained by lower home-indoor pollutant levels and more time spent in less polluted home-outdoor environment by pregnant women in greener areas.

To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR). 23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10(th) centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10(th) centile with normal UA Doppler and delivery >35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10(th) centile. (1)H nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data. The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR. IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.

Implementation of universal antiretroviral treatment (ART) in pregnancy has improved maternal health and reduced vertical transmission. However, women living with HIV (WLHIV) still experience worse perinatal outcomes. This retrospective study compared demographic, virological factors, ART regimens and perinatal outcomes in pregnant WLHIV between 2000–2010 (n = 318) and 2011–2021 (n = 140) at a tertiary center in Barcelona. Significant demographic shifts included changes in ethnic distribution, substance use, educational attainment, and maternal BMI. Significant progress in infection control was observed, with increased ART coverage up to 97%, improved viral suppression (80% to 91.3%, p = 0.002), and enhanced immunological status. ART regimens shifted significantly, with an increase in integrase strand transfer inhibitors (INSTI)-based regimens (0.7% to 39.2%, p < 0.001). Obstetric management evolved, with a rise in vaginal deliveries (24.8% to 44.3%, p < 0.001) and a decline in intrapartum zidovudine (93.7% to 54.7%, p < 0.001). Notably, preterm birth rates sharply declined, yet small-for-gestational-age (SGA) infants (26.4% vs. 20%, p = 0.323) and preeclampsia rates remained unchanged and higher than in the general population. All statistical analyses were performed in IBM SPSS statistics 23. In conclusion, although maternal and perinatal outcomes in pregnant WLHIV have improved over the past two decades, a high rate of adverse perinatal outcomes related to placental dysfunction (SGA, preeclampsia) persist. Our findings highlight the need for optimized prenatal care and further research to develop targeted interventions for WLHIV.

Objective: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. Patients and Methods: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). Results: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. Conclusions: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

Available evidence concerning the association between air pollution and preeclampsia is limited, and specific associations with early- and late-onset preeclampsia have not been assessed. We investigated the association, if any, between preeclampsia (all, early-, and late-onset) and exposure to nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5; fine particles), ≤ 10 μm, and 2.5-10 μm, and PM2.5 light absorption (a proxy for elemental carbon) during the entire pregnancy and during the first, second, and third trimesters. This study was based on 8,398 pregnancies (including 103 cases of preeclampsia) among women residing in Barcelona, Spain (2000-2005). We applied a spatiotemporal exposure assessment framework using land use regression models to predict ambient pollutant levels during each week of pregnancy at the geocoded residence address of each woman at the time of birth. Logistic and conditional logistic regression models were used to estimate unadjusted and adjusted associations. We found positive associations for most of our evaluated outcome-exposure pairs, with the strongest associations observed for preeclampsia and late-onset preeclampsia in relation to the third-trimester exposure to fine particulate pollutants, and for early-onset preeclampsia in relation to the first-trimester exposure to fine particulate pollutants. Among our investigated associations, those of first- and third-trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia attained statistical significance. We observed increased risk of preeclampsia associated with exposure to fine particulate air pollution. Our findings, in combination with previous evidence suggesting distinct pathogenic mechanisms for early- and late-onset preeclampsia, support additional research on this topic.

Vaginal Escherichia coli colonization is related to obstetric infections and the consequent development of infections in newborns. Ampicillin resistance among E. coli strains is increasing, which is the main choice for treating empirically many obstetric and neonatal infections. Vaginal E. coli strains are very similar to extraintestinal pathogenic E. coli with regards to the virulence factors and the belonging to phylogroup B2. We studied the antimicrobial resistance and the genetic virulence profile of 82 E. coli isolates from 638 vaginal samples and 63 isolated from endometrial aspirate, placental and amniotic fluid samples from pregnant women with obstetric infections. The prevalence of E. coli in the vaginal samples was 13%, which was significant among women with associated risk factors during pregnancy, especially premature preterm rupture of membranes (p<0.0001). Sixty-five percent of the strains were ampicillin-resistant. The E. coli isolates causing obstetric infections showed higher resistance levels than vaginal isolates, particularly for gentamicin (p = 0.001). The most prevalent virulence factor genes were those related to the iron uptake systems revealing clear targets for interventions. More than 50% of the isolates belonged to the virulent B2 group possessing the highest number of virulence factor genes. The ampicillin-resistant isolates had high number of virulence factors primarily related to pathogenicity islands, and the remarkable gentamicin resistance in E. coli isolates from women presenting obstetric infections, the choice of the most appropriate empiric treatment and clinical management of pregnant women and neonates should be carefully made. Taking into account host-susceptibility, the heterogeneity of E. coli due to evolution over time and the geographical area, characterization of E. coli isolates colonizing the vagina and causing obstetric infections in different regions may help to develop interventions and avoid the aetiological link between maternal carriage and obstetric and subsequent puerperal infections.

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.