Maternal uterine artery blood flow is critical to maintaining the intrauterine environment, permitting normal placental function, and supporting fetal growth. It has long been believed that ...inadequate transformation of the maternal uterine vasculature is a consequence of primary defective trophoblast invasion and leads to the development of preeclampsia. That early pregnancy maternal uterine artery perfusion is strongly associated with placental cellular function and behaviour has always been interpreted in this context. Consistently observed changes in pre-conceptual maternal and uterine artery blood flow, abdominal pregnancy implantation, and late pregnancy have been challenging this concept, and suggest that abnormal placental perfusion may result in trophoblast impairment, rather than the other way round. This review focuses on evidence that maternal cardiovascular function plays a significant role in the pathophysiology of preeclampsia.
Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including ...117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I
= 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I
= 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.
The COVID-19 pandemic has had a profound impact on health-care systems and potentially on pregnancy outcomes, but no systematic synthesis of evidence of this effect has been undertaken. We aimed to ...assess the collective evidence on the effects on maternal, fetal, and neonatal outcomes of the pandemic.
We did a systematic review and meta-analysis of studies on the effects of the pandemic on maternal, fetal, and neonatal outcomes. We searched MEDLINE and Embase in accordance with PRISMA guidelines, from Jan 1, 2020, to Jan 8, 2021, for case-control studies, cohort studies, and brief reports comparing maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. We also planned to record any additional maternal and offspring outcomes identified. Studies of solely SARS-CoV-2-infected pregnant individuals, as well as case reports, studies without comparison groups, narrative or systematic literature reviews, preprints, and studies reporting on overlapping populations were excluded. Quantitative meta-analysis was done for an outcome when more than one study presented relevant data. Random-effects estimate of the pooled odds ratio (OR) of each outcome were generated with use of the Mantel-Haenszel method. This review was registered with PROSPERO (CRD42020211753).
The search identified 3592 citations, of which 40 studies were included. We identified significant increases in stillbirth (pooled OR 1·28 95% CI 1·07–1·54; I2=63%; 12 studies, 168 295 pregnancies during and 198 993 before the pandemic) and maternal death (1·37 1·22–1·53; I2=0%, two studies both from low-income and middle-income countries, 1 237 018 and 2 224 859 pregnancies) during versus before the pandemic. Preterm births before 37 weeks' gestation were not significantly changed overall (0·94 0·87–1·02; I2=75%; 15 studies, 170 640 and 656 423 pregnancies) but were decreased in high-income countries (0·91 0·84–0·99; I2=63%; 12 studies, 159 987 and 635 118 pregnancies), where spontaneous preterm birth was also decreased (0·81 0·67–0·97; two studies, 4204 and 6818 pregnancies). Mean Edinburgh Postnatal Depression Scale scores were higher, indicating poorer mental health, during versus before the pandemic (pooled mean difference 0·42 95% CI 0·02–0·81; three studies, 2330 and 6517 pregnancies). Surgically managed ectopic pregnancies were increased during the pandemic (OR 5·81 2·16–15·6; I2=26%; three studies, 37 and 272 pregnancies). No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; hypertensive disorders of pregnancy; preterm birth before 34 weeks', 32 weeks', or 28 weeks' gestation; iatrogenic preterm birth; labour induction; modes of delivery (spontaneous vaginal delivery, caesarean section, or instrumental delivery); post-partum haemorrhage; neonatal death; low birthweight (<2500 g); neonatal intensive care unit admission; or Apgar score less than 7 at 5 min.
Global maternal and fetal outcomes have worsened during the COVID-19 pandemic, with an increase in maternal deaths, stillbirth, ruptured ectopic pregnancies, and maternal depression. Some outcomes show considerable disparity between high-resource and low-resource settings. There is an urgent need to prioritise safe, accessible, and equitable maternity care within the strategic response to this pandemic and in future health crises.
None.
Objective We sought to evaluate the association between fetal cerebroplacental ratio (CPR) and intrapartum fetal compromise and admission to the neonatal unit (NNU) in term pregnancies. Study Design ...This was a retrospective cohort study in a single tertiary referral center over a 14-year period from 2000 through 2013. The umbilical artery pulsatility index, middle cerebral artery pulsatility index, and CPR were recorded within 2 weeks of delivery. The birthweight (BW) values were converted into centiles and Doppler parameters converted into multiples of median (MoM), adjusting for gestational age using reference ranges. Logistic regression analysis was performed to identify, and adjust for, potential confounders. Results The study cohort included 9772 singleton pregnancies. The rates of operative delivery for presumed fetal compromise and neonatal admission were 17.2% and 3.9%, respectively. Doppler CPR MoM was significantly lower in pregnancies requiring operative delivery or admission to NNU for presumed fetal compromise ( P < .01). On multivariate logistic regression, both CPR MoM and BW centile were independently associated with the risk of operative delivery for presumed fetal compromise (adjusted odds ratio OR, 0.67; 95% confidence interval CI, 0.52–0.87; P = .003 and adjusted OR, 0.994; 95% CI, 0.992–0.997; P < .001, respectively). The latter associations persisted even after exclusion of small-for-gestational-age cases from the cohort. Multivariate logistic regression also demonstrated that CPR MoM was an independent predictor for NNU admission at term (adjusted OR, 0.55; 95% CI, 0.33–0.92; P = .021), while BW centile was not (adjusted OR, 1.00; 95% CI, 0.99–1.00; P = .794). The rates of operative delivery for presumed fetal compromise were significantly higher for appropriate-for-gestational-age fetuses with low CPR MoM (22.3%) compared to small-for-gestational-age fetuses with normal CPR MoM (17.3%). Conclusion Lower fetal CPR, regardless of the fetal size, was independently associated with the need for operative delivery for presumed fetal compromise and with NNU admission at term. The extent to which fetal hemodynamic status could be used to predict perinatal morbidity and optimize the mode of delivery merits further investigation.
The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical ...length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies.
Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI 0.59, 0.91, p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI 0.57, 0.84, p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% CI 0.43, 0.67, 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI 0.23, 0.97, p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% CI 0.99, 3.66, p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI 0.25, 0.60, p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI 0.53, 0.90, p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI 0.58, 0.95, p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI 0.57, 0.80, p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low.
Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.
AbstractObjectiveTo determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease ...2019 (covid-19).DesignLiving systematic review and meta-analysis.Data sourcesMedline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists.Study selectionCohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.Data extractionAt least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.Results192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19.ConclusionPregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit.Systematic review registrationPROSPERO CRD42020178076.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
The COVID-19 pandemic has been at the forefront of medicine over the last few years. Pregnant women are often exposed to infectious agents that can be harmful not only to the mother but also to the ...foetus. Moreover, changes during pregnancy means that pregnant women have increased vulnerability to viral infections, especially pulmonary infections. Epidemiological studies have shown a link between maternal viral infections and miscarriage, preterm birth as well as congenital defects. With potential poor outcomes for both women and their newborns, having a good understanding of the presentation and management of these viral pulmonary infections is essential. The increased risk of adverse outcomes has been highlighted during the COVID-19, SARS and H1N1 influenza pandemics.
•Changes during pregnancy mean that women have increased vulnerability to viral infections, especially pulmonary infections.•The increased risk of adverse outcomes in pregnant women has been highlighted during various pandemics.•Pregnant women should be counselled regarding the efficacy and safety of preventative methods such as the COVID mRNA vaccines.
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.
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.
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.
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.
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.
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.
Objective Fetal cerebroplacental ratio is emerging as a better proxy than birthweight for placental insufficiency and as a marker of fetal compromise at term. The extent to which these fetal Doppler ...changes are related to neonatal outcomes has not been systematically assessed. The main aim of this study was to evaluate the association between estimated fetal weight percentile, cerebroplacental ratio recorded at 34+0 –35+6 weeks’ gestation, and neonatal unit admission at term. Study Design This was a retrospective cohort study in a tertiary referral center over an 11 year period from 2002 to 2012. The umbilical artery pulsatility index (PI), middle cerebral artery PI, and cerebroplacental ratio were recorded at 34+0 –35+6 weeks. Weight values were converted into percentiles and Doppler parameters into multiples of the median (MoM), adjusting for gestational age. Logistic regression analysis was performed to identify, and adjust for, potential confounders. Results We identified 2518 pregnancies in which a scan was performed at 34+0 –35+6 weeks and delivery occurred at or beyond 37 weeks. In the 2485 pregnancies included in the analysis, the umbilical artery PI MoM was significantly higher, and the middle cerebral artery PI and cerebroplacental ratio MoM significantly lower in the babies requiring neonatal unit admission ( P < .05). However, the estimated fetal weight percentile was not significantly different between those who required neonatal unit admission and those who did not ( P = .087). According to multivariate logistic regression, cerebroplacental ratio MoM (odds ratio, 0.39; 95% confidence interval, 0.19–0.79; P = .008) and gestational age at delivery (odds ratio, 0.70; 95% confidence interval, 0.61–0.80; P < .001) were significantly associated with the risk of neonatal unit admission, whereas maternal age and birthweight percentile were not ( P = .183 and P = .460, respectively). Irrespective of birthweight or estimated fetal weight percentile, the fetal cerebroplacental ratio appears to be a better predictor of the need for neonatal unit admission ( P < .001). Conclusion Lower cerebroplacental ratio and gestational age at delivery, but not fetal size, were independently associated with the need for admission to the neonatal unit at term in a high-risk patient group. The extent to which fetal hemodynamic assessment could be used to predict perinatal morbidity and optimize the timing of delivery merits further investigation.
Flu vaccine allocation is of great importance for safeguarding public health and mitigating the impact of influenza outbreaks. In this regard, decision-makers face multifaceted challenges, including ...limited vaccine supply, targeting vulnerable people, adapting to regional variations, ensuring fairness in distribution, and promoting public trust. The objective of this work is to address the vaccination allocation problem by introducing a novel optimization scheme with the simulated annealing (SA) algorithm. A dual-objective model is developed to both manage infection rates and minimize the unit cost of the vaccination campaign. The proposed approach is designed to promote convergence toward the best Pareto front in multi-objective optimization, wherein SA attempts to embed diversity and uniformity within a memetic version of the controlled elitism nondominated sorting genetic algorithm (CENSGA). To model the underlying vaccination allocation problem, the dynamics of the disease are described using the susceptible–exposed–infectious–recovered (SEIR) epidemiological model to better express hidden flu characteristics. This model specifically analyzes the effects of pulsive vaccination allocation in two phases aiming to minimize the number of infected individuals to an acceptable level in a finite amount of time, which can help in stabilizing the model against sudden flu endemics over the long run. The computational experiments show that the proposed algorithm effectively explores the extensive search space of the vaccination allocation problem. The results of the suggested framework indicate that the obtained Pareto front best represents complete vaccination campaigns. The findings of this research can help in evidence-based decision making that can optimize flu vaccine distribution, contribute to the prevention of illness and reduction in hospitalizations, and potentially save countless lives.
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