Abstract
Background: The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development?
Methods: Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes.
Findings: This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated.
Interpretation: Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies
Abstract
Screening of retinopathy of prematurity (ROP) was modified in a level-3 neonatal intensive care unit by the introduction of a wide-field retinal imaging. The aim of this study was to evaluate whether retinopathy of prematurity (ROP) diagnosis was improved or not compared to previously used binocular indirect ophthalmoscopy (BIO). This was a retrospective, uncontrolled, quality improvement project. Records of consecutive premature newborns screened for ROP over two 1-year periods were reviewed. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. ROP screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (Panocam™ pro) in 2019. Records of N = 297 patients were analyzed (N = 159 in 2014 and N = 138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n = 46/138, 33.1%) compared to 2014 (n = 11/159, 6.9%) (p < 0.0001). Most neonates presented with mild forms of ROP during both 1-year periods analyzed. After adjustment for all parameters influencing ROP occurrence, the variables contributing independently to the diagnosis of any stage of ROP were birth weight (p = 0.002), duration of mechanical ventilation (p = 0.028) and wide-field fundus camera-assisted screening (p < 0.001).
Conclusion: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated with higher ROP detection.
What is known: • No consensus has been reached to replace binocular indirect ophthalmoscopy by retinal imaging for ROP screening. • Diagnostic accuracy and high sensitivity and specificity has been reported for wide-field digital imaging.
What is new: • The introduction of wide-field imaging for ROP screening in at level-3 reference center was independently associated to higher ROP detection.
Abstract
Objectives: The objectives were to describe mortality and causes of death in children with intraventricular hemorrhage (IVH) and to study neurodevelopmental outcomes.
Methods: The study was a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. Children were recruited in 2011. A standardized assessment was conducted at age 5. Children born before 32 weeks’ gestation and admitted to a NICU were eligible. Exposure was IVH defined by the Papile classification. Main outcomes were mortality, causes of death, and neurodevelopmental outcomes at age 5.
Results: Among the 3468 children included, 578 (16.7%) had grade 1 IVH, 424 (12.2%) grade 2 IVH, and 114 (3.3%) grade 3 IVH; 144 (4.1%) had intraparenchymal hemorrhage (IPH). Mortality was 29.7% (36 of 114) for children with grade 3 IVH and 74.4% (109 of 144) for those with IPH; 67.6% (21 of 31) and 88.7% (86 of 97) of deaths, respectively, were because of withholding and withdrawing of life-sustaining treatment. As compared with no IVH, low-grade IVH was not associated with measured neurodevelopmental disabilities at age 5. High-grade IVH was associated with moderate and severe neurodevelopmental disabilities, reduced full-scale IQ, and cerebral palsy.
Conclusions: Rates of neurodevelopmental disabilities at age 5 did not differ between children without IVH and those with low-grade IVH. For high-grade IVH, mortality rate was high, mostly because of withholding and withdrawal of life-sustaining treatment, and we found a strong association with overall neurodevelopmental disabilities in survivors.
Abstract
Although the 2022 Monkeypox virus epidemic mostly affects males, particularly men having sex with men, transmission to women may also occur. In case of MPXV infection in pregnancy, transmission to the fetus can result in very severe disease. Thus, caregivers should be aware of the measures to be taken according to the available evidence, in case of exposure or in case of symptoms particularly skin rash compatible with this diagnosis in a pregnant woman. Pregnant women should have access to vaccination, vaccinia immunoglobulin or antiviral medications as required.
Abstract
Introduction: Nicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment.
Case report: We present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period.
Conclusion: This case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients.
Abstract
Introduction: The global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFβ, and IL-1β) in asymptomatic women with and without subsequent spontaneous preterm delivery.
Material and methods: We used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks’ gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups.
Clinicaltrials: gov: NCT00718705.
Results: Between July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFβ, and IL-1β were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFβ, and IL-1β levels did not differ between the groups.
Conclusions: In amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.
Abstract
Objective: To assess the risk of gestational hypertension (GH) and pre-eclampsia (PE) during a second pregnancy after occurrence during a first pregnancy.
Design: Prospective cohort study.
Setting: CONCEPTION is a French nationwide cohort study that used data from the National Health Data System (SNDS) database.
Methods: We included all women who gave birth for the first time in France in 2010-2018 and who subsequently gave birth. We identified GH and PE through hospital diagnoses and the dispensing of anti-hypertensive drugs. The incidence rate ratios (IRR) of all hypertensive disorder of pregnancy (HDP) during the second pregnancy were estimated using Poisson models adjusted for confounding.
Main outcome measures: Incidence rate ratios of HDP during the second pregnancy.
Results: Of the 2 829 274 women included, 238 506 (8.4%) were diagnosed with HDP during their first pregnancy. In women with GH during their first pregnancy, 11.3% (IRR 4.5, 95% confidence interval [CI] 4.4-4.7) and 3.4% (IRR 5.0, 95% CI 4.8-5.3) developed GH and PE during their second pregnancy, respectively. In women with PE during their first pregnancy, 7.4% (IRR 2.6, 95% CI 2.5-2.7) and 14.7% (IRR 14.3, 95% CI 13.6-15.0) developed GH and PE during their second pregnancy, respectively. The more severe and earlier the PE during the first pregnancy, the stronger the likelihood of having PE during the second pregnancy. Maternal age, social deprivation, obesity, diabetes and chronic hypertension were all associated with PE recurrence.
Conclusion: These results can guide policymaking that focuses on improving counselling for women who wish to become pregnant more than once, by identifying those who would benefit more from tailored management of modifiable risk factors, and heightened surveillance during post-first pregnancies.
Abstract
Background: Many clinical trials have reported that low-dose aspirin decreases the risk of pre-eclampsia in women with prior pre-eclampsia. However, its impact in a real-world population has not been fully assessed.
Objectives: To assess the rates of low-dose aspirin initiation during pregnancy in women with a history of pre-eclampsia, and to evaluate the impact of low-dose aspirin in prevention of pre-eclampsia recurrence in a real-world population.
Study design: CONCEPTION is a French nationwide cohort study which uses data from the country’s National Health Data System database. We included all women in France who gave birth at least twice between 2010-2018, and who had pre-eclampsia during their first pregnancy. Every dispensing of low-dose aspirin (75-300 mg) between the beginning of their second pregnancy and 36 weeks of gestation (WG) was identified. We used Poisson regression models to estimate the adjusted incidence rate ratios (aIRRs) of receiving aspirin at least once during their second pregnancy. In women who had early and/or severe pre-eclampsia during their first pregnancy, we estimated the IRRs of pre-eclampsia recurrence during their second pregnancy according to the aspirin therapy.
Results: In 28,467 women who were included in the study, the aspirin initiation rate during the second pregnancy ranged from 27.8% for women in whose first pregnancy the pre-eclampsia was mild and late, to 79.9% for those women whose pre-eclampsia was severe and early. Just over half (54.3%) of those treated with aspirin-initiated treatment before 16 WG and adhered to treatment. Compared with women with mild and late pre-eclampsia, the aIRRs (95% CI) for receiving aspirin at least once during the second pregnancy were 1.94 (1.86-2.03) for women with severe and late pre-eclampsia, 2.34 (2.17-2.52) for those with early and mild pre-eclampsia, and 2.87 [2.74-3.01] for those with early and severe pre-eclampsia E. Social deprivation was associated with a lower initiation of aspirin (IRR = 0.74 [0.70-0.78]). Aspirin was not associated with a lower risk of mild and late pre-eclampsia, severe and late pre-eclampsia, or mild and early pre-eclampsia during the second pregnancy. The aIRRs for severe and early pre-eclampsia during the second pregnancy were 0.77 (0.62-0.95) for women who received prescribed aspirin at least once, 0.71 (0.5-0.89) for those who initiated aspirin therapy before 16 WG, and 0.60 (0.47-0.77) for those who adhered to aspirin treatment throughout their second pregnancy. The risk of severe and early pre-eclampsia was lower only when the prescribed mean daily dose was ≥ 100 mg/day.
Conclusion: In women with a history of pre-eclampsia, aspirin initiation during a second pregnancy and adherence to the prescribed dosage were largely insufficient, especially for women experiencing social deprivation. Aspirin initiated before 16 WG at a dose ≥ 100 mg/day was associated with a lower risk of severe and early pre-eclampsia.
Abstract
Objective: To investigate whether extrauterine growth restriction (EUGR) during the neonatal hospitalisation by sex among extremely preterm (EPT) infants is associated with cerebral palsy (CP) and cognitive and motor abilities at 5 years of age.
Study design: Population-based cohort of births <28 weeks of gestation with data from obstetric and neonatal records and parental questionnaires and clinical assessments at 5 years of age.
Setting: 11 European countries.
Patients: 957 EPT infants born in 2011-2012.
Main outcomes: EUGR at discharge from the neonatal unit was defined as (1) the difference between Z-scores at birth and discharge with <-2 SD as severe, -2 to -1 SD as moderate using Fenton’s growth charts (Fenton) and (2) average weight-gain velocity using Patel’s formula in grams (g) per kilogram per day (Patel) with <11.2 g (first quartile) as severe, 11.2-12.5 g (median) as moderate. Five-year outcomes were: a CP diagnosis, intelligence quotient (IQ) using the Wechsler Preschool and Primary Scales of Intelligence tests and motor function using the Movement Assessment Battery for Children, second edition.
Results: 40.1% and 33.9% children were classified as having moderate and severe EUGR, respectively, by Fenton and 23.8% and 26.3% by Patel. Among children without CP, those with severe EUGR had lower IQ than children without EUGR (-3.9 points, 95% Confidence Interval (CI)=-7.2 to -0.6 for Fenton and -5.0 points, 95% CI=-8.2 to -1.8 for Patel), with no interaction by sex. No significant associations were observed between motor function and CP.
Conclusions: Severe EUGR among EPT infants was associated with decreased IQ at 5 years of age.