Research Letter
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Research Letter
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Objectives: This study measured the impact of the first wave of COVID-19 pandemic (COVID-19) (March-April 2020) on the incidence of bloodstream infections (BSIs) at Assistance Publique – Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France.
Methods: The number of patient admission blood cultures (BCs) collected, number of positive BCs, and antibiotic resistance and consumption were analysed retrospectively for the first quarter of 2020, and also for the first quarter of 2019 for comparison, in 25 APHP hospitals (ca. 14 000 beds).
Results: Up to a fourth of patients admitted in March-April 2020 in these hospitals had COVID-19. The BSI rate per 100 admissions increased overall by 24% in March 2020 and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to third-generation cephalosporins (3GC) was also observed in March-April 2020, particularly in K. pneumoniae, enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae…), and P. aeruginosa. A concomitant increase in 3GC consumption occurred.
Conclusions: The COVID-19 pandemic had a strong impact on hospital management and also unfavourable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.
Aims : Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and foetal morbidity and mortality. We aimed to estimate the impact of HDP on the onset of chronic hypertension in primiparous women in the first years following childbirth.
Methods and results : This nationwide cohort study used data from the French National Health Data System (SNDS). All eligible primiparous women without pre-existing chronic hypertension who delivered between 2010 and 2018 were included. Women were followed up from six weeks post-partum until onset of hypertension, a cardiovascular event, death, or the study end date (31 December 2018). The main outcome was a diagnosis of chronic hypertension. We used Cox models to estimate hazard ratios (HRs) of chronic hypertension for all types of HDP. Overall, 2 663 573 women were included with a mean follow-up time of 3.0 years. Among them, 180 063 (6.73%) had an HDP. Specifically 66 260 (2.16%) had pre-eclampsia (PE) and 113 803 (4.27%) had gestational hypertension (GH). Compared with women who had no HDP, the fully adjusted HRs of chronic hypertension were 6.03 [95% confidence interval (CI) 5.89-6.17] for GH, 8.10 (95% CI 7.88-8.33) for PE (all sorts), 12.95 (95% CI 12.29-13.65) for early PE, 9.90 (95% CI 9.53-10.28) for severe PE, and 13.17 (95% CI 12.74-13.60) for PE following GH. Hypertensive disorders of pregnancy exposure duration was an additional risk factor of chronic hypertension for all PE subgroups. Women with HDP consulted a general practitioner or cardiologist more frequently and earlier.
Conclusion : Hypertensive disorders of pregnancy exposure greatly increased the risk of chronic hypertension in the first years following delivery.
Peroxisome proliferator-activated receptor γ (PPARγ) is essential for placental development, whose SNPs have shown increased susceptibility to pregnancy-related diseases, such as preeclampsia. Our aim was to investigate the association between preeclampsia and three PPARγ SNPs (Pro12Ala, C1431T, and C681G), which together with nine clinical factors were used to build a pragmatic model for preeclampsia prediction. Data were collected from 1648 women from the EDEN cohort, of which 35 women had preeclamptic pregnancies, and the remaining 1613 women had normal pregnancies. Univariate analysis comparing preeclamptic patients to the control resulted in the SNP C1431T being the only factor significantly associated with preeclampsia (p < 0.05), with a confidence interval of 95% and odds ratio ranging from 4.90 to 8.75. On the other hand, three methods of multivariate feature selection highlighted seven features that could be potential predictors of preeclampsia: maternal C1431T and C681G variants, obesity, body mass index, number of pregnancies, primiparity, cigarette use, and education. These seven features were further used as input into eight different machine-learning algorithms to create predictive models, whose performances were evaluated based on metrics of accuracy and the area under the receiver operating characteristic curve (AUC). The boost tree-based model performed the best, with respective accuracy and AUC values of 0.971 ± 0.002 and 0.991 ± 0.001 in the training set and 0.951 and 0.701 in the testing set. A flowchart based on the boost tree model was constructed to depict the procedure for preeclampsia prediction. This final decision tree showed that the C1431T variant of PPARγ is significantly associated with susceptibility to preeclampsia. We believe that this final decision tree could be applied in the clinical prediction of preeclampsia in the very early stages of pregnancy.
Polyhydramnios is a common feature diagnosed by ultrasound in the second half of pregnancy. Biochemical analysis of amniotic fluid can be useful when suspecting Bartter syndrome or digestive atresia but in most of cases, no etiology of polyhydramnios is found because of the complex regulation of amniotic fluid. Aquaporins (AQP) are transmembrane channel proteins contributing to water transfers. Some of them are expressed in fetal membranes and placenta. Their expression has been shown to be disrupted in some pathological conditions such as maternal diabetes, often associated with polyhydramnios. AQP-1, 3 and 8 levels in amniotic fluid were retrospectively measured in patients suffering from polyhydramnios (n=21) from 23 weeks of gestation (WG). They were compared to the levels observed in control subjects (n=96) and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels were physiologically fluctuating, AQP-1 levels always being the lowest and AQP-3 the highest, with a significant decrease at the end of pregnancy. AQPs/AFP ratios increased about 8 folds during pregnancy, their kinetic profiles reflecting physiological dynamic evolution of amniotic fluid volume. In polyhydramnios, AQP-3 level tended to be decreased whereas AQP-8 level was decreased from mid-gestation whatever the etiology of polyhydramnios. No significant relationship was found between AQPs levels and either the fetal prematurity degree or macrosomia. No specific pattern was observed in idiopathic polyhydramnios, limiting the interest of AQPs dosage in amniotic fluid in the management of those complicated pregnancies.
We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks’ gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks’ gestation and of composite adverse neonatal outcomes at >26 weeks’ gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible.
The burden of congenital toxoplasmosis has become small in France today, in particular as a result of timely therapy for pregnant women, fetuses and newborns. Thus, the French screening and prevention program has been evaluated and recently confirmed despite a decline over time in the incidence of toxoplasmosis. Serological diagnosis of maternal seroconversion is usually simple but can be difficult when the first trimester test shows the presence of IgM, requiring referral to an expert laboratory. Woman with confirmed seroconversion should be referred quickly to an expert center, which will decide with her on treatment and antenatal diagnosis. Although the level of proof is moderate, there is a body of evidence in favor of active prophylactic prenatal treatment started as early as possible (ideally within 3 weeks of seroconversion) to reduce the risk of maternal-fetal transmission, as well as symptoms in children. The recommended therapies to prevent maternal-fetal transmission are: (1) spiramycin in case of maternal infection before 14 gestational weeks; (2) pyrimethamine and sulfadiazine (P-S) with folinic acid in case of maternal infection at 14 WG or more. Amniocentesis is recommended to guide prenatal and neonatal care. If fetal infection is diagnosed by PCR on amniotic fluid, therapy with P-S should be initiated as early as possible or continued in order reduce the risk of damage to the brain or eyes. Further research is required to validate new approaches to preventing congenital toxoplasmosis.
Objective: Very preterm born children are at risk for impairments in multiple neurodevelopmental domains, but outcomes vary between individuals. The present study aimed to distinguish subgroups with distinct profiles of functioning across motor, cognitive, behavioral, and psychosocial domains. These profiles were related to neonatal and social/environmental factors.
Method: The sample included 1977 children born very preterm (<32 weeks’ gestation) in 2011 from the French population-based EPIPAGE-2 cohort. Using latent profile analysis, subgroups of children were distinguished based on their functioning at 5.5 years. The relation between outcome profiles and neonatal and social/environmental factors was tested using multivariable multinomial logistic regression analysis.
Results: Four subgroups with distinct outcome profiles were distinguished: no deficit in any domain (45%); motor and cognitive deficits without behavioral/psychosocial deficits (31%); primarily behavioral and psychosocial deficits (16%); and deficits in multiple domains (8%). Male sex (odds ratio [OR] = 2.1-2.7), bronchopulmonary dysplasia (OR = 2.1-2.8), low parental education level (OR = 1.8-2.1), and parental non-European immigrant status (OR = 2.3-3.0) were independently associated with higher odds for all suboptimal outcome profiles compared to the favorable outcome profile.
Conclusion: Among 5.5-year-old very preterm born children, subgroups can be distinguished with distinct outcome profiles that vary in severity, type, and combinations of deficits. This information is important for the development of interventions that are tailored to the needs of large subgroups of children across multiple domains of functioning. General neonatal and social/environmental factors may be useful for early identification of very preterm born children at risk for general rather than domain-specific impairments.
Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts.
Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2-3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor’s/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years.
Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results.
Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.
Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity.