Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders

Objective: To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design: A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxicischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results: Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2-3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1-4.3). Conclusion: When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor

Volatilome analyses and in vitro antimicrobial activity of the essential oils from five south african helichrysum species

Helichrysum genus was used in folk South African medicine to treat various human disorders. As a part of our on-going research addressing the exploitation of South African plants belonging to this genus, five species were investigated for their volatile and antimicrobial activities. The volatile organic compounds (VOCs) and the essential oils (EOs) were analysed by gas chromatography mass spectrometry (GC-MS). Microdilution was the method used for assessing both antimycotic and antibacterial activities, which was also tested by Kirby-Bauer agar disc diffusion. Total monoterpenes (TMs) dominated the VOCs of four species (H. trilineatum (70.6%), H. edwardsii (79.3%), H. cooperi (84.5%), and H. pandurifolium (57.0%)). H. cooperi and H. edwardsii EOs showed the predominance of TMs (68.2% and 84.5%, respectively), while H. pandurifolium and H. trilineatum EOs were characterized by the prevalence of TSs (86.5% and 43.6%, respectively). H. odoratissimum EO evidenced a similar amount of both TMs (49.5%) and TSs (46.4%). Microsporum canis was more sensitive to these EOs. The lowest minimum inhibitory concentration (MIC) was observed with H. pandurifolium and H. edwardsii EOs (0.25%). H. pandurifolium and H. trilineatum had a good effect on Staphylococcus aureus (MIC 5%). These findings open new perspectives for the exploitation of these natural compounds for application in cosmetics and pharmaceutics

RELATION BETWEEN MATERNAL THROMBOPHILIA AND STILLBIRTH ACCORDING TO CAUSES/ASSOCIATED CONDITIONS OF DEATH

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95\% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95\%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95\% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia

Stillbirths at Term : Case Control Study of Risk Factors, Growth Status and Placental Histology

Objective: To investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births. Methods: A retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; 90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions. Results: There was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight ( 643\ub0percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%; p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR. Conclusion: The assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses. \ua9 2016 Mecacci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Vaccination against SARS-CoV-2 in pregnancy during the Omicron wave: the prospective cohort study of the Italian obstetric surveillance system

Objectives: Evidence on the effects of the SARS-CoV-2 Omicron variant on vaccinated and unvaccinated pregnant women is sparse. This study aimed to compare maternal and perinatal outcomes of women infected with SARS-CoV-2 during the Omicron wave in Italy, according to their vaccine protection.Methods: This national prospective cohort study enrolled pregnant women with a positive SARS-CoV-2 nasopharyngeal swab within 7 days of hospital admission between 1 January and 31 May, 2022. Women who received at least one dose of vaccine during pregnancy and those who completed the vaccine cycle with the first booster were considered protected against moderate or severe COVID-19 (MSCD). A multivariable logistic regression model evaluated the association between vaccine protection and disease severity. Maternal age, educational level, citizenship, area of birth, previous comorbidities, and obesity were analysed as potential risk factors. Results: MSCD was rare (41/2147, 1.9%; 95% CI, 1.4-2.6), and the odds of developing it were significantly higher among unprotected women (OR, 2.78; 95% CI, 1.39-5.57). Compared with protected women (n = 1069), the unprotected (n = 1078) were more often younger, with lower educational degrees, and foreigners. A higher probability of MSCD was found among women with previous comorbidities (OR, 2.86; 95% CI, 1.34-6.12) and those born in Asian countries (OR, 3.05; 95% CI, 1.23-7.56). The percentage of preterm birth was higher among women with MSCD compared with milder cases (32.0% [8/25] versus 8.4% [161/1917], p < 0.001) as well as the percentage of caesarean section (52.0% [13/25] versus 31.6% [606/1919], p 0.029). Discussion: Although severe maternal and perinatal outcomes were rare, their prevalence was significantly higher among women without vaccine protection. Vaccination during pregnancy has the potential to protect both the mother and the baby, and it is therefore strongly recommended. Edoardo Corsi Decenti, Clin Microbiol Infect 2023;29:772 (c) 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Autoimmune diseases and pregnancy: analysis of a series of cases

BACKGROUND: An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. METHODS: The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. RESULTS: The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid function over the years and first trimester miscarriage, suffered a second miscarriage despite clinical stability and antibody regression. CONCLUSIONS: As described in literature, the authors found a strong association between autoimmune disease and obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome and autoimmune thyroiditis

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Hypertension and chronic kidney disease (CKD) have a significant impact on global morbidity and mortality. The Low Birth Weight and Nephron Number Working Group has prepared a consensus document aimed to address the relatively neglected issue for the developmental programming of hypertension and CKD. It emerged from a workshop held on April 2, 2016, including eminent internationally recognized experts in the field of obstetrics, neonatology, and nephrology. Through multidisciplinary engagement, the goal of the workshop was to highlight the association between fetal and childhood development and an increased risk of adult diseases, focusing on hypertension and CKD, and to suggest possible practical solutions for the future. The recommendations for action of the consensus workshop are the results of combined clinical experience, shared research expertise, and a review of the literature. They highlight the need to act early to prevent CKD and other related noncommunicable diseases later in life by reducing low birth weight, small for gestational age, prematurity, and low nephron numbers at birth through coordinated interventions. Meeting the current unmet needs would help to define the most cost-effective strategies and to optimize interventions to limit or interrupt the developmental programming cycle of CKD later in life, especially in the poorest part of the world

Do differences in diagnostic criteria for late fetal growth restriction matter?

Background: Criteria for diagnosis of fetal growth restriction differ widely according to national and international guidelines, and further heterogeneity arises from the use of different biometric and Doppler reference charts, making the diagnosis of fetal growth restriction highly variable. Objective: This study aimed to compare fetal growth restriction definitions between Delphi consensus and Society for Maternal-Fetal Medicine definitions, using different standards/charts for fetal biometry and different reference ranges for Doppler velocimetry parameters. Study design: From the TRUFFLE 2 feasibility study (856 women with singleton pregnancy at 32+0 to 36+6 weeks of gestation and at risk of fetal growth restriction), we selected 564 women with available mid-pregnancy biometry. For the comparison, we used standards/charts for estimated fetal weight and abdominal circumference from Hadlock, INTERGROWTH-21st, and GROW and Chitty. Percentiles for umbilical artery pulsatility index and its ratios with middle cerebral artery pulsatility index were calculated using Arduini and Ebbing reference charts. Sensitivity and specificity for low birthweight and adverse perinatal outcome were evaluated. Results: Different combinations of definitions and reference charts identified substantially different proportions of fetuses within our population as having fetal growth restriction, varying from 38% (with Delphi consensus definition, INTERGROWTH-21st biometric standards, and Arduini Doppler reference ranges) to 93% (with Society for Maternal-Fetal Medicine definition and Hadlock biometric standards). None of the different combinations tested appeared effective, with relative risk for birthweight <10th percentile between 1.4 and 2.1. Birthweight <10th percentile was observed most frequently when selection was made with the GROW/Chitty charts, slightly less with the Hadlock standard, and least frequently with the INTERGROWTH-21st standard. Using the Ebbing Doppler reference ranges resulted in a far higher proportion identified as having fetal growth restriction compared with the Arduini Doppler reference ranges, whereas Delphi consensus definition with Ebbing Doppler reference ranges produced similar results to those of the Society for Maternal-Fetal Medicine definition. Application of Delphi consensus definition with Arduini Doppler reference ranges was significantly associated with adverse perinatal outcome, with any biometric standards/charts. The Society for Maternal-Fetal Medicine definition could not accurately detect adverse perinatal outcome irrespective of estimated fetal weight standard/chart used. Conclusion: Different combinations of fetal growth restriction definitions, biometry standards/charts, and Doppler reference ranges identify different proportions of fetuses with fetal growth restriction. The difference in adverse perinatal outcome may be modest, but can have a significant impact in terms of rate of intervention