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1.
Front Immunol ; 13: 825075, 2022.
Article in English | MEDLINE | ID: covidwho-1834402

ABSTRACT

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.


Subject(s)
Abortion, Habitual , COVID-19 , Chorioamnionitis , Abortion, Habitual/etiology , Abortion, Habitual/pathology , Chorioamnionitis/pathology , Chronic Disease , Female , Fetal Death/etiology , Fetal Growth Retardation/etiology , Fetal Growth Retardation/pathology , Fibrin , Humans , Placenta/pathology , Pregnancy , Pregnancy Outcome , SARS-CoV-2 , Syndrome
2.
West Afr J Med ; 39(4): 355-361, 2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1824273

ABSTRACT

BACKGROUND: In order to reduce COVID-19 transmission and protect healthcare workers, the outpatient departments (OPDs) in many hospitals worldwide were closed down in the early days of the pandemic. Patients being managed for chronic medical illnesses who subsequently suffered reduced access to healthcare have been described as "the patients left behind". AIM: The study aimed at assessing the impact of the closure of the Medical OPD in University of Ilorin Teaching Hospital (UITH) on the health and perceived well-being of patients with chronic medical illnesses. METHODS: A cross-sectional study of 180 patients with chronic medical illnesses attending the MOPD in UITH. RESULTS: Mean age of participants was 50.2±18.2years, 92 (51.1%) were male, median duration of attending MOPD was 21 months (IQR 12-36). 92 patients (51.1%) perceived a negative affectation of their well-being by the closure of MOPD. Being >50 years was associated with a perception of negative affectation of well-being (P=0.042). 140 patients (77.8%) had clinic appointments that fell within the period under review. 67(69.3%) of the 97 patients who had medical complaints during the period could not reach a doctor and this was associated with a perception of negative affectation of their wellbeing. The commonest action they took was to do nothing (28.3%), three (4.5%) resorted to herbal concoctions. 19 (29.9%) felt their complaints were urgent. CONCLUSION: Our study identifies that patients with chronic medical illness are potential victims of COVID-19 related disruption of healthcare services. Healthcare managers in Nigeria must develop alternatives such as telemedicine that sustain face-to-face medical interaction during eventualities.


CONTEXTE: Afin de réduire la transmission de la COVID-19 et protéger les travailleurs de la santé, les services ambulatoires (OPD) dans de nombreux hôpitaux dans le monde ont été fermés dans les premiers jours de l'Pandémie. Patients pris en charge pour des maladies chroniques quipar la suite souffert d'un accès réduit aux soins de santé ont été décrit comme "les patients laissés pour compte". OBJECTIF: L'étude visait à évaluer l'impact de la fermeture de l'OPD médical à l'hôpital universitaire d'Ilorin (UITH) la santé et le bien-être perçu des patients atteints de chroniquesMaladies. MÉTHODES: Une étude transversale de 180 patients atteints de chroniques maladies médicales fréquentant le MOPD à l'UITH. RÉSULTATS: L'âge moyen des participants était de 50.2 ±18.2 ans, 92 ans(51.1 %) étaient des hommes, la durée médiane de la participation au MOPD était de 21mois (IQR 12-36). 92 patients (51.1 %) ont perçu un résultat negative l'affectation de leur bien-être par la fermeture du MOPD. Être >50ans était associée à une perception d'affectation négative de bien-être (P= 0.042). 140 patients (77.8 %) avaient des rendez-vous à la clinique qui s'inscrivait dans la période considérée. 67 (69.3 %) des 97 patients qui ont eu des problèmes médicaux au cours de la période n'ont pas pu atteindre un et cela était associé à une perception d'affectation negative de leur bien-être. L'action la plus courante qu'ils ont prise était de ne rien faire (28.3%), deux (4.5%) ont eu recours à des concoctions à base de plantes. 19 (29.9 %) ont ressenti leurs plaintes étaient urgentes. CONCLUSION: Notre étude identifie que les patients atteints demaladie chronique les maladies médicales sont des victimes potentielles des perturbations liées à la COVID-19des services de santé. Les gestionnaires de soins de santé au Nigeria doivent se developper des solutions de rechange comme la télémédecine qui soutiennent la médecine en personne interaction lors d'éventualités. Mots-clés: Maladie COVID-19, Maladies chroniques, COVID-19 fermeture connexe des services médicaux ambulatoires, perception.


Subject(s)
COVID-19 , Outpatients , Adult , Aged , Ambulatory Care , Cross-Sectional Studies , Dwarfism , Female , Fetal Growth Retardation , Humans , Male , Microcephaly , Middle Aged , Osteochondrodysplasias , Perception
3.
PLoS One ; 17(3): e0265147, 2022.
Article in English | MEDLINE | ID: covidwho-1745312

ABSTRACT

PURPOSE: To investigate changes in the number of preterm infants, low birth weight infants, and infants with fetal growth restriction (FGR) or retinopathy of prematurity (ROP) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this retrospective cross-sectional study, we reviewed the medical records of infants born and admitted to the neonatal intensive care unit and growth care unit of Shiga University of Medical Science Hospital before the COVID-19 pandemic (April 1, 2019 to September 30, 2019) and during the pandemic (April 1, 2020 to September 30, 2020). Medical records of infants' mothers were also collected. Preterm infants, low birth weight infants, infants with FGR, infant and maternal factors associated with FGR, and infants requiring treatment for ROP were compared between the two periods. RESULTS: There were fewer infants born at < 28 weeks of gestation, infants with birth weight < 1,500 g, and infants with FGR during the pandemic period than the pre-pandemic period (pre-pandemic: n = 4 vs. during pandemic: n = 0, P = 0.048; pre-pandemic: n = 15 vs. during pandemic: n = 6, P = 0.02; and pre-pandemic: n = 31 vs. during pandemic: n = 12, P = 0.0002, respectively). There were no significant differences in any infant or maternal factors associated with FGR. The number of infants requiring treatment for ROP decreased during the pandemic, although this difference was not statistically significant (pre-pandemic: n = 3 vs. during pandemic: n = 0, P = 0.08). CONCLUSIONS: Our findings showed a reduction in the number of infants with FGR during the COVID-19 pandemic. The number of infants born at < 28 weeks of gestation and infants with birth weight < 1,500 g also decreased during the pandemic period. There was a trend toward fewer infants requiring treatment for ROP during the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , Fetal Growth Retardation/epidemiology , Infant, Premature , Retinopathy of Prematurity/epidemiology , Birth Weight , Cross-Sectional Studies , Female , Gestational Age , Humans , Infant, Low Birth Weight , Infant, Newborn , Intensive Care Units, Neonatal , Japan/epidemiology , Male , Retrospective Studies
4.
Am J Physiol Regul Integr Comp Physiol ; 321(6): R833-R843, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1541942

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound protein containing 805 amino acids. ACE2 shows approximately 42% sequence similarity to somatic ACE but has different biochemical activities. The key role of ACE2 is to catalyze the vasoconstrictor peptide angiotensin (ANG) II to Ang-(1-7), thus regulating the two major counterbalancing pathways of the renin-angiotensin system (RAS). In this way, ACE2 plays a protective role in end-organ damage by protecting tissues from the proinflammatory actions of ANG II. The circulating RAS is activated in normal pregnancy and is essential for maintaining fluid and electrolyte homeostasis and blood pressure. Renin-angiotensin systems are also found in the conceptus. In this review, we summarize the current knowledge on the regulation and function of circulating and uteroplacental ACE2 in uncomplicated and complicated pregnancies, including those affected by preeclampsia and fetal growth restriction. Since ACE2 is the receptor for SARS-CoV-2, and COVID-19 in pregnancy is associated with more severe disease and increased risk of abnormal pregnancy outcomes, we also discuss the role of ACE2 in mediating some of these adverse consequences. We propose that dysregulation of ACE2 plays a critical role in the development of preeclampsia, fetal growth restriction, and COVID-19-associated pregnancy pathologies and suggest that human recombinant soluble ACE2 could be a novel therapeutic to treat and/or prevent these pregnancy complications.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Placenta/enzymology , Pregnancy Complications/enzymology , Renin-Angiotensin System , Uterus/enzymology , Angiotensin-Converting Enzyme 2/therapeutic use , Animals , Blood Pressure , COVID-19/enzymology , COVID-19/physiopathology , COVID-19/virology , Female , Fetal Growth Retardation/enzymology , Fetal Growth Retardation/physiopathology , Humans , Inflammation Mediators/metabolism , Placenta/physiopathology , Pre-Eclampsia/enzymology , Pre-Eclampsia/physiopathology , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/physiopathology , Pregnancy Complications, Infectious/enzymology , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Uterus/physiopathology , Water-Electrolyte Balance
5.
Eur Rev Med Pharmacol Sci ; 25(18): 5876-5884, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1451047

ABSTRACT

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARS-COV-2 infection, irrespectively of his/her age.


Subject(s)
COVID-19/epidemiology , Disease Susceptibility/epidemiology , Fetal Development , Disease Susceptibility/virology , Fetal Growth Retardation , Humans , Infant, Low Birth Weight , Severity of Illness Index , Young Adult
6.
Front Immunol ; 12: 743022, 2021.
Article in English | MEDLINE | ID: covidwho-1450814

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.


Subject(s)
COVID-19/pathology , Placenta/pathology , Placenta/virology , Pregnancy Complications, Infectious/virology , Abortion, Spontaneous/virology , Angiotensin-Converting Enzyme 2/metabolism , Female , Fetal Growth Retardation/virology , Humans , Maternal-Fetal Exchange/physiology , Pregnancy , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Stillbirth
7.
J Obstet Gynaecol Res ; 47(12): 4232-4240, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1443299

ABSTRACT

OBJECTIVE: We aimed to investigate the incidence of adverse pregnancy outcomes including preterm birth, preeclampsia (PE), and fetal growth restriction (FGR) in pregnant women with COVID-19 according to the gestational age. METHODS: This retrospective study included 167 pregnant women who were hospitalized with confirmed COVID-19. The patients were divided into three groups according to the time of diagnosis as follows: <12 weeks of gestation (first trimester, n = 10), 12-24 weeks of gestation (n = 28), and >24 weeks of gestation (n = 129). Medical records of the patients were reviewed retrospectively and adverse pregnancy outcomes were analyzed. RESULTS: A total of 49 (29.3%) patients had an active COVID-19 infection at the time of delivery, while 118 (70.7%) gave birth after the infection was cleared. Twenty-three patients had preterm birth and the gestational age was <34 weeks in only four of these patients. There was no significant difference in the preterm birth, PE, FGR, HELLP syndrome, and gestational diabetes mellitus among the three gestation groups (p = 0.271, 0.394, 0.403, 0.763, and 0.664, respectively). Four (2.39%) patients required intensive care unit stay. Maternal death was seen in only one (0.59%) patient. CONCLUSION: Our study showed no significant correlation between the gestational age at the time of COVID-19 infection and the frequency of adverse pregnancy outcomes such as preterm birth, PE, FGR, and gestational diabetes mellitus. However, further studies are needed to draw a firm conclusion on this topic.


Subject(s)
COVID-19 , Premature Birth , Female , Fetal Growth Retardation/epidemiology , Gestational Age , Humans , Infant , Infant, Newborn , Pregnancy , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Retrospective Studies , SARS-CoV-2
9.
Minerva Obstet Gynecol ; 73(4): 471-481, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1348831

ABSTRACT

Fetal growth restriction is one of the most common obstetric complications, affecting 7-10% of all pregnancies. Affected fetuses are exposed to an adverse environment in utero during a critical time of development and may face long-term health consequences such as increased cardiovascular risk in adulthood. Growth restricted fetuses develop remodeled hearts with signs of systolic and diastolic dysfunction. Cardiac adaptations are more evident in early severe cases, but also present in late onset fetal growth restriction. Cardiovascular remodeling persists into postnatal life, from the neonatal period to adolescence, encompassing an increased susceptibility to adult disease. In this review, we summarize the current evidence on cardiovascular programming associated to fetal growth restriction, its postnatal consequences and potential strategies to reduce their cardiovascular risk.


Subject(s)
Cardiovascular System , Fetal Growth Retardation , Adolescent , Adult , Female , Fetus , Heart , Humans , Infant, Newborn , Pregnancy , Ventricular Remodeling
10.
BMJ Open ; 11(6): e049120, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1288394

ABSTRACT

INTRODUCTION: Fetal growth restriction (FGR) is a major contributor to fetal and neonatal morbidity and mortality with intrauterine, neonatal and lifelong complications. This study explores maternal obstructive sleep apnoea (OSA) as a potentially modifiable risk factor for FGR. We hypothesise that, in pregnancies complicated by FGR, treating mothers who have OSA using positive airway pressure (PAP) will improve birth weight and neonatal outcomes. METHODS AND ANALYSIS: The Sleep Apnea and Fetal Growth Restriction study is a prospective, block-randomised, single-blinded, multicentre, pragmatic controlled trial. We enrol pregnant women aged 18-50, between 22 and 31 weeks of gestation, with established FGR based on second trimester ultrasound, who do not have other prespecified known causes of FGR (such as congenital anomalies or intrauterine infection). In stage 1, participants are screened by questionnaire for OSA risk. If OSA risk is identified, participants proceed to stage 2, where they undergo home sleep apnoea testing. Participants are determined to have OSA if they have an apnoea-hypopnoea index (AHI) ≥5 (if the oxygen desaturation index (ODI) is also ≥5) or if they have an AHI ≥10 (even if the ODI is <5). These participants proceed to stage 3, where they are randomised to nightly treatment with PAP or no PAP (standard care control), which is maintained until delivery. The primary outcome is unadjusted birth weight; secondary outcomes include fetal growth velocity on ultrasound, enrolment-to-delivery interval, gestational age at delivery, birth weight corrected for gestational age, stillbirth, Apgar score, rate of admission to higher levels of care (neonatal intensive care unit or special care nursery) and length of neonatal stay. These outcomes are compared between PAP and control using intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Boards at Washington University in St Louis, Missouri; Hadassah Hebrew University Medical Center, Jerusalem; and the University of Rochester, New York. Recruitment began in Washington University in November 2019 but stopped from March to November 2020 due to COVID-19. Recruitment began in Hadassah Hebrew University in March 2021, and in the University of Rochester in May 2021. Dissemination plans include presentations at scientific conferences and scientific publications. TRIAL REGISTRATION NUMBER: NCT04084990.


Subject(s)
COVID-19 , Sleep Apnea, Obstructive , Female , Fetal Growth Retardation , Humans , Infant, Newborn , Missouri , Multicenter Studies as Topic , New York , Pregnancy , Prospective Studies , Randomized Controlled Trials as Topic , SARS-CoV-2 , Stillbirth , Washington
11.
PLoS One ; 16(6): e0253796, 2021.
Article in English | MEDLINE | ID: covidwho-1282315

ABSTRACT

BACKGROUND: Prior studies have demonstrated an increased stillbirth rate. It was suggested that the COVID-19 pandemic may have impacted on attendances for reduced fetal movements. Thus, we sought to ascertain the impact of the pandemic on attendances for reduced fetal movements (RFM) in our unit, ultrasound provision for reduced fetal movements, and the stillbirth rate. METHODS: This was a single site retrospective cohort study involving all women complaining of a 1st episode of reduced fetal movements between 01/03/2020-30/04/2020 (COVID) to 01/03/2019-30/04/2019 (Pre-COVID). Data were retrieved from computerised hospital records and statistical analyses were performed using GraphPad Prism and SPSS. RESULTS: 22% (179/810) of women presented with a 1st episode of reduced fetal movements Pre-COVID compared to 18% (145/803) during COVID (p = 0.047). Primiparous women were significantly over-represented in this population with a 1.4-fold increase in attendances during COVID (67% vs 48%, p = 0.0005). Neither the total stillbirth rate nor the stillbirth rate amongst women who presented with reduced fetal movements changed during COVID. Ultrasound provision was not impacted by COVID with 95% of the scans performed according to local guidelines, compared to Pre-COVID (74%, p = 0.0001). CONCLUSIONS: There is a significant decrease in 1st attendances for reduced fetal movements during COVID-19 pandemic. Primiparous women were 1.4 times more likely to attend with RFM. Women should be reassured that COVID-19 has not resulted in a decreased provision of care for RFM, and has not impacted on the stillbirth rate.


Subject(s)
COVID-19/epidemiology , Fetal Growth Retardation , Fetal Movement , SARS-CoV-2 , Stillbirth/epidemiology , Ultrasonography, Prenatal , Adult , Female , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/epidemiology , Gestational Age , Humans , Pregnancy , Retrospective Studies
12.
Ginekol Pol ; 92(5): 383-386, 2021.
Article in English | MEDLINE | ID: covidwho-1207900

ABSTRACT

It is now more than a year since the first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease (COVID-19) was diagnosed in China. Current data suggest that pregnancy may not only be a risk factor for the development of severe forms of COVID-19, but that the SARS-CoV-2 infection may impact on common pregnancy complications as well. Healthy pregnant women are likely to be more susceptible to viral infection and therefore are at higher risk of developing severe COVID-19 because of adaptive changes in their immune and respiratory systems, their altered endothelial cell functions, and modified coagulation responses. However, studies show that most pregnant women diagnosed with COVID-19 developed mild-to-moderate symptoms and only a few of them have required critical care facilities. In contrast with preeclampsia, preeclampsia-like syndrome can resolve spontaneously following recovery from severe pneumonia and may not be an obstetric indication for delivery. Preeclampsia-like syndrome is one symptom of COVID-19, but its cause is different from obstetric preeclampsia and therefore not connected with placental failure. Vertical transmission of SARS-CoV-2 infection is rare but can probably occur. No evidence has been found that COVID-19 developed during pregnancy leads to unfavourable outcomes in the fetus. Most health authorities indicate that standard procedures should be used when managing pregnancy complications in asymptomatic women with confirmed SARS-CoV-2. Vaccines should not be withheld from pregnant and lactating individuals who otherwise meet the vaccination criteria.


Subject(s)
COVID-19/epidemiology , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , COVID-19/prevention & control , Female , Fetal Growth Retardation/epidemiology , Humans , Infectious Disease Transmission, Vertical/prevention & control , Personal Protective Equipment , Pre-Eclampsia/epidemiology , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Premature Birth/epidemiology
13.
Medicina (Kaunas) ; 57(3)2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1167648

ABSTRACT

Background and Objectives: COVID-19, a disease caused by SARS-CoV-2, is a public health emergency. Data on the effect of the virus on pregnancy are limited. Materials and Methods: We carried out a retrospective descriptive study, in order to evaluate the obstetric results on pregnant women in which SARS-CoV-2 was detected through RT-PCR of the nasopharyngeal swab, at admission to the maternity hospital. Results: From 16 March to 31 July 2020, 12 SARS-CoV-2 positive pregnant women have been hospitalized. Eleven were hospitalized for initiation or induction of labor, corresponding to 0.64% of deliveries in the maternity hospital. One pregnant woman was hospitalized for threatened abortion, culminating in a stillbirth at 20 weeks of gestation. Regarding the severity of the disease, nine women were asymptomatic and three had mild illness (two had associated cough and one headache). Three had relevant environmental exposure and a history of contact with infected persons. None had severe or critical illness due to SARS-CoV-2. There were no maternal deaths. The following gestational complications were observed: one stillbirth, one preterm labor, one preterm prelabor rupture of membranes, and one fetal growth restriction. Four deliveries were eutocic, two vacuum-assisted deliveries and five were cesarean sections. The indications for cesarean section were obstetric. Conclusions: SARS-CoV-2 infection was found in a minority of hospitalized pregnant women in this sample. Most are asymptomatic or have mild illness, from gestational complications to highlight stillbirth and preterm birth. There were no cases of vertical transmission by coronavirus.


Subject(s)
COVID-19/epidemiology , Pregnancy Complications, Infectious/epidemiology , Adult , COVID-19/physiopathology , Cesarean Section , Cough/physiopathology , Female , Fetal Growth Retardation/epidemiology , Fetal Membranes, Premature Rupture/epidemiology , Headache/physiopathology , Hospitalization , Hospitals, Maternity , Humans , Labor, Induced , Obstetric Labor, Premature/epidemiology , Portugal/epidemiology , Postpartum Hemorrhage/epidemiology , Pregnancy , Pregnancy Outcome , Premature Birth/epidemiology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Stillbirth/epidemiology , Vacuum Extraction, Obstetrical
14.
Ultrasound Obstet Gynecol ; 57(4): 573-581, 2021 04.
Article in English | MEDLINE | ID: covidwho-1162971

ABSTRACT

OBJECTIVE: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry. METHODS: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection. RESULTS: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM. CONCLUSIONS: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy Outcome/epidemiology , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , Female , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/virology , Humans , Infant, Newborn , Infant, Small for Gestational Age , Infectious Disease Transmission, Vertical/statistics & numerical data , Male , Maternal Mortality , Pandemics , Perinatal Death , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , Premature Birth/diagnosis , Premature Birth/epidemiology , Premature Birth/virology , Registries , Stillbirth/epidemiology , United Kingdom/epidemiology , United States/epidemiology
15.
Viruses ; 13(3)2021 03 10.
Article in English | MEDLINE | ID: covidwho-1125677

ABSTRACT

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS-CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.


Subject(s)
COVID-19/transmission , Fetal Growth Retardation/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/physiology , Adult , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Fatal Outcome , Female , Fetal Growth Retardation/mortality , Fetal Growth Retardation/pathology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Pregnancy , Pregnancy Complications, Infectious/mortality , Pregnancy Complications, Infectious/pathology , Pregnancy Trimester, Second , SARS-CoV-2/genetics
16.
Am J Obstet Gynecol MFM ; 2(2): 100107, 2020 05.
Article in English | MEDLINE | ID: covidwho-1064726

ABSTRACT

Objective: The aim of this systematic review was to report pregnancy and perinatal outcomes of coronavirus spectrum infections, and particularly coronavirus 2019 (COVID-19) disease because of severe acute respiratory syndrome-coronavirus-2 infection during pregnancy. Data Sources: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for coronavirus or severe acute respiratory syndrome or SARS or Middle East respiratory syndrome or MERS or COVID-19 and pregnancy. The search and selection criteria were restricted to English language. Study Eligibility Criteria: Inclusion criteria were hospitalized pregnant women with a confirmed coronavirus related-illness, defined as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), or COVID-19. Study Appraisal and Synthesis Methods: We used meta-analyses of proportions to combine data and reported pooled proportions, so that a pooled proportion may not coincide with the actual raw proportion in the results. The pregnancy outcomes observed included miscarriage, preterm birth, preeclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score <7 at 5 minutes, neonatal asphyxia, admission to a neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results: Nineteen studies including 79 hospitalized women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (82.6%), cough (57.1%), and dyspnea (27.0%). For all coronavirus infections, the pooled proportion of miscarriage was 64.7% (8/12; 95% confidence interval, 37.9-87.3), although reported only for women affected by SARS in two studies with no control group; the pooled proportion of preterm birth <37 weeks was 24.3% (14/56; 95% confidence interval, 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (6/34; 95% confidence interval, 9.5-34.9), preeclampsia in 16.2% (2/19; 95% confidence interval, 4.2-34.1), and fetal growth restriction in 11.7% (2/29; 95% confidence interval, 3.2-24.4), although reported only for women affected by SARS; 84% (50/58) were delivered by cesarean; the pooled proportion of perinatal death was 11.1% (5/60; 95% confidence interval, 84.8-19.6), and 57.2% of newborns (3/12; 95% confidence interval, 3.6-99.8) were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth <37 weeks, occurring in 41.1% of cases (14/32; 95% confidence interval, 25.6-57.6), while the pooled proportion of perinatal death was 7.0% (2/41; 95% confidence interval, 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion: In hospitalized mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, preterm birth is the most common adverse pregnancy outcome. COVID-19 infection was associated with higher rate (and pooled proportions) of preterm birth, preeclampsia, cesarean, and perinatal death. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy, although they should be interpreted with caution in view of the very small number of included cases.


Subject(s)
Abortion, Spontaneous/epidemiology , COVID-19/epidemiology , Fetal Growth Retardation/epidemiology , Fetal Membranes, Premature Rupture/epidemiology , Pre-Eclampsia/epidemiology , Pregnancy Complications, Infectious/epidemiology , Premature Birth/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Cesarean Section/statistics & numerical data , Coronavirus Infections/epidemiology , Female , Hospitalization , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Intensive Care Units, Neonatal/statistics & numerical data , Middle East Respiratory Syndrome Coronavirus , Perinatal Death , Pregnancy , Pregnancy Outcome/epidemiology , SARS Virus , SARS-CoV-2
17.
Pediatr Pulmonol ; 55(1): 229-235, 2020 01.
Article in English | MEDLINE | ID: covidwho-1064409

ABSTRACT

BACKGROUND: In utero diaphragm development is critically important for postnatal respiratory function and any disturbance to fetal development may lead to diaphragm dysfunction and respiratory complications in the postnatal period. Intrauterine growth restriction (IUGR) has been shown to affect respiratory function in a sex-dependent manner; however, the effect of IUGR on diaphragm function is unknown. AIM: This study used a maternal hypoxia-induced mouse model of IUGR to investigate the impact of IUGR on diaphragm function and structure in male and female adult offspring. MATERIALS AND METHODS: Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2 ) from gestational days 11 to 17.5 and then returned to normoxic conditions. Control mice were housed under normoxic conditions throughout pregnancy. At 8 weeks of age, offspring were euthanized and diaphragms isolated for functional assessment in organ bath experiments and for histological analysis. RESULTS: IUGR offspring were lighter at birth and remained lighter at 8 weeks of age compared to Controls. While diaphragm force (maximal or twitch) was not affected by treatment or sex, the IUGR group exhibited a longer half-relaxation time after twitch contractions compared to Control. Female offspring had a lower maximum rate of force development and higher fatigue resistance compared to males, independent of IUGR. There was no difference in the diaphragm myofibre cross-sectional area between groups or sexes. CONCLUSION: Sex and IUGR independently affect diaphragm contraction in adult mice without changes in structure. This study demonstrates that IUGR affects diaphragm contractile function in later life and could impair respiratory function if exacerbated under conditions of increased respiratory load.


Subject(s)
Diaphragm/physiopathology , Fetal Growth Retardation/physiopathology , Animals , Disease Models, Animal , Female , Fetal Growth Retardation/etiology , Hypoxia/complications , Hypoxia/physiopathology , Male , Mice , Mice, Inbred BALB C , Pregnancy
18.
J Reprod Immunol ; 143: 103250, 2021 02.
Article in English | MEDLINE | ID: covidwho-939094

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic has spread rapidly across the world. The vast majority of patients with COVID-19 manifest mild to moderate symptoms but may progress to severe cases or even mortalities. Young adults of reproductive age are the most affected population by SARS-CoV-2 infection. However, there is no consensus yet if pregnancy contributes to the severity of COVID-19. Initial studies of pregnant women have found that COVID-19 significantly increases the risk of preterm birth, intrauterine growth restriction, and low birth weight, which have been associated with non-communicable diseases in offspring. Besides, maternal viral infections with or without vertical transmission have been allied with neurological and behavioral disorders of the offspring. In this review, obstetrical outcomes of women with COVID-19 and possible risks for their offspring are discussed by reviewing maternal immune responses to COVID-19 based on the current evidence. Structural and systemic follow-up of offspring who are exposed to SARS-CoV-2 in-utero is suggested.


Subject(s)
COVID-19/immunology , Child of Impaired Parents , Fetal Growth Retardation/epidemiology , Pregnancy Complications, Infectious/immunology , Premature Birth/epidemiology , SARS-CoV-2/physiology , COVID-19/epidemiology , COVID-19/transmission , Female , Humans , Immunity, Maternally-Acquired , Infectious Disease Transmission, Vertical , Maternal Exposure/adverse effects , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Problem Behavior , Risk
20.
Mult Scler ; 26(10): 1137-1146, 2020 09.
Article in English | MEDLINE | ID: covidwho-727247

ABSTRACT

Concerns regarding infection with the novel coronavirus SARS-CoV-2 leading to COVID-19 are particularly marked for pregnant women with autoimmune diseases such as multiple sclerosis (MS). There is currently a relative paucity of information to guide advice given to and the clinical management of these individuals. Much of the limited available data around COVID-19 and pregnancy derives from the obstetric literature, and as such, neurologists may not be familiar with the general principles underlying current advice. In this article, we discuss the impact of potential infection on the pregnant woman, the impact on her baby, the impact of the current pandemic on antenatal care, and the interaction between COVID-19, MS and pregnancy. This review provides a framework for neurologists to use to guide the individualised advice given to both pregnant women with MS, and those women with MS who are considering pregnancy. This includes evidence derived from previous novel coronavirus infections, and emerging evidence from the current pandemic.


Subject(s)
Coronavirus Infections/immunology , Immunologic Factors/therapeutic use , Multiple Sclerosis/drug therapy , Pneumonia, Viral/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications/drug therapy , Betacoronavirus , Breast Feeding , COVID-19 , Delivery of Health Care , Delivery, Obstetric , Disease Susceptibility , Female , Fetal Growth Retardation , Humans , Multiple Sclerosis/immunology , Pandemics , Preconception Care , Pregnancy , Pregnancy Complications/immunology , Premature Birth , Prenatal Care , Recurrence , SARS-CoV-2
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