Impact of telehealth implementation on diagnosis of hypertensive disorders of pregnancy.

BACKGROUND: COVID-19 caused a rapid integration of telehealth into prenatal care. This raises questions about the ability to screen for hypertensive disorders of pregnancy when caring for patients remotely. OBJECTIVE: This study aimed to assess the effect of telehealth adaptation on the timing and severity of diagnosis of hypertensive disorders of pregnancy. STUDY DESIGN: This was a retrospective study of patients with hypertensive disorders of pregnancy who delivered from April 2019 to October 2019 (before the pandemic) and April 2020 to October 2020 (during the pandemic) at 1 urban tertiary care center. The primary outcome was mean gestational age at diagnosis of a hypertensive disorder of pregnancy. The secondary outcomes included severity of diagnosis, both initially and at the time of delivery. The results were adjusted for baseline characteristic difference at P<.10, using multivariable logistic regression and analysis of covariance, as appropriate. The sample size was calculated based on a previous cohort study of patients who developed preeclampsia, with a mean gestational age at delivery of 36.3 weeks and a standard deviation of 2.8 weeks. A sample size of 124 patients would be needed per group to detect a gestational age difference of 1 week with 80% power and a 95% confidence interval. RESULTS: Overall, 498 patients were included, with 231 from 2019 and 267 from 2020. Of note, 17.1% of patients had preeclampsia with severe features initially, and 29.3% of patients met the criteria at delivery. In 2020, 80.5% of patients used telehealth (vs 0.9% of patients in 2019), doing so for a mean of 29.0% of prenatal appointments. Unadjusted and adjusted analyses showed no significant difference in gestational age at diagnosis or diagnosis severity between cohorts. In the adjusted analysis, cohort year was not significantly associated with severity of initial diagnosis (adjusted odds ratio, 0.86; 95% confidence interval, 0.53-1.39; P=.53) or severity of diagnosis at delivery (adjusted odds ratio, 0.97; 95% confidence interval, 0.64-1.46; P=.87). However, Black race was significantly associated with increased risk of having severe preeclampsia at initial diagnosis (adjusted odds ratio, 1.70; 95% confidence interval, 1.01-2.85; P=.046). In addition, Black race (adjusted odds ratio, 2.62; 95% confidence interval, 1.60-4.28; P<.001), Hispanic ethnicity (adjusted odds ratio for non-Hispanic, 0.40; 95% confidence interval, 0.19-0.82; P=.01), and initial body mass index (adjusted odds ratio, 1.04; 95% confidence interval, 1.01-1.06; P=.005) were significantly associated with a diagnosis of severe preeclampsia at delivery. CONCLUSION: The adaptation of telehealth was not associated with delays in the diagnosis of hypertensive disorders of pregnancy or with increased severity of diagnoses.

Remote blood pressure monitoring in high risk pregnancy - study protocol for a randomised controlled trial (REMOTE CONTROL trial).

BACKGROUND: Pregnant women at high risk for developing a hypertensive disorder of pregnancy require frequent antenatal assessments, especially of their blood pressure. This expends significant resources for both the patient and healthcare system. An alternative to in-clinic assessments is a remote blood pressure monitoring strategy, in which patients self-record their blood pressure at home using a validated blood pressure machine. This has the potential to be cost-effective, increase patient satisfaction, and reduce outpatient visits, and has had widespread uptake recently given the increased need for remote care during the ongoing COVID-19 pandemic. However robust evidence supporting this approach over a traditional face-to-face approach is lacking, and the impact on maternal and foetal outcomes has not yet been reported. Thus, there is an urgent need to assess the efficacy of remote monitoring in pregnant women at high risk of developing a hypertensive disorder of pregnancy. METHODS: The REMOTE CONTROL trial is a pragmatic, unblinded, randomised controlled trial, which aims to compare remote blood pressure monitoring in high-risk pregnant women with conventional face-to-face clinic monitoring, in a 1:1 allocation ratio. The study will recruit patients across 3 metropolitan Australian teaching hospitals and will evaluate the safety, cost-effectiveness, impact on healthcare utilisation and end-user satisfaction of remote blood pressure monitoring. DISCUSSION: Remote blood pressure monitoring is garnering interest worldwide and has been increasingly implemented following the COVID-19 pandemic. However, robust data regarding its safety for maternofoetal outcomes is lacking. The REMOTE CONTROL trial is amongst the first randomised controlled trials currently underway, powered to evaluate maternal and foetal outcomes. If proven to be as safe as conventional clinic monitoring, major potential benefits include reducing clinic visits, waiting times, travel costs, and improving delivery of care to vulnerable populations in rural and remote communities. TRIAL REGISTRATION: The trial has been prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12620001049965p, on October 11th, 2020).

Augmented Intelligence for Clinical Discovery in Hypertensive Disorders of Pregnancy Using Outlier Analysis.

Objectives Clinical discoveries are heralded by observing unique and unusual clinical cases. The effort of identifying such cases rests on the shoulders of busy clinicians. We assess the feasibility and applicability of an augmented intelligence framework to accelerate the rate of clinical discovery in preeclampsia and hypertensive disorders of pregnancy-an area that has seen little change in its clinical management. Methods We conducted a retrospective exploratory outlier analysis of participants enrolled in the folic acid clinical trial (FACT, N=2,301) and the Ottawa and Kingston birth cohort (OaK, N=8,085). We applied two outlier analysis methods: extreme misclassification contextual outlier and isolation forest point outlier. The extreme misclassification contextual outlier is based on a random forest predictive model for the outcome of preeclampsia in FACT and hypertensive disorder of pregnancy in OaK. We defined outliers in the extreme misclassification approach as mislabelled observations with a confidence level of more than 90%. Within the isolation forest approach, we defined outliers as observations with an average path length z score less or equal to -3, or more or equal to 3. Content experts reviewed the identified outliers and determined if they represented a potential novelty that could conceivably lead to a clinical discovery. Results In the FACT study, we identified 19 outliers using the isolation forest algorithm and 13 outliers using the random forest extreme misclassification approach. We determined that three (15.8%) and 10 (76.9%) were potential novelties, respectively. Out of 8,085 participants in the OaK study, we identified 172 outliers using the isolation forest algorithm and 98 outliers using the random forest extreme misclassification approach; four (2.3%) and 32 (32.7%), respectively, were potential novelties. Overall, the outlier analysis part of the augmented intelligence framework identified a total of 302 outliers. These were subsequently reviewed by content experts, representing the human part of the augmented intelligence framework. The clinical review determined that 49 of the 302 outliers represented potential novelties.  Conclusions Augmented intelligence using extreme misclassification outlier analysis is a feasible and applicable approach for accelerating the rate of clinical discoveries. The use of an extreme misclassification contextual outlier analysis approach has resulted in a higher proportion of potential novelties than using the more traditional point outlier isolation forest approach. This finding was consistent in both the clinical trial and real-world cohort study data. Using augmented intelligence through outlier analysis has the potential to speed up the process of identifying potential clinical discoveries. This approach can be replicated across clinical disciplines and could exist within electronic medical records systems to automatically identify outliers within clinical notes to clinical experts.

Obstetric Disorders and Critical Illness.

In this article, we discuss some of the more common obstetric-related conditions that can lead to critical illness and require management in an ICU. These include the hypertensive disorders of pregnancy, postpartum hemorrhage, hemolysis, elevated liver enzymes, and low platelet syndrome, acute fatty liver of pregnancy, amniotic fluid embolism, and peripartum cardiomyopathy. We also discuss pulmonary embolism and Covid-19. Despite not being specific to obstetric patients, pulmonary embolism is a common, life-threatening diagnosis in pregnancy with particular risks and management aspects. Covid-19 does not seem to occur with higher frequency in pregnant women, but it leads to higher rates of ICU admissions and mechanical ventilation in pregnant women than in their nonpregnant peers. Its prevalence during our current global pandemic makes it important to discuss in this article. We provide a basis for critical care physicians to be engaged in informed conversations and management in a multidisciplinary manner with other relevant providers in the care of critically ill pregnant and postpartum women.

Role of biomarkers (sFlt-1/PlGF) in cases of COVID-19 for distinguishing preeclampsia and guiding clinical management.

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS). STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed. MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics and clinical outcomes. RESULTS: A total of 97 SARS-CoV-2 unvaccinated women with suspected infection were considered, 76 were COVID-19 positive cases and 21 COVID-19 negative. Among COVID-19 positive cases, 09 presented with SARS and 11 were diagnosed with PE, of which 6 had SARS-CoV-2 infection in first and second trimester (04 with sFlt-1/PlGF ≥ 38) and 05 with PE and COVID-19 diagnosed at the same time, during third trimester (03 with sFlt-1/PlGF ≥ 38). Five presented with PE with severe features. sFlt-1/PlGF ratio was significantly higher in the COVID-19 positive/PE positive group compared to COVID-19 positive/PE negative group (p-value = 0.005), with no increase in cases complicated by SARS. CONCLUSIONS: sFlt-1/PlGF ratio could be a useful tool for differential diagnosis and adequate counseling among cases of COVID-19 and PE, especially if severe disease. COVID-19 early in pregnancy could potentially be a risk factor for PE later during gestation.

First- or second-trimester SARS-CoV-2 infection and subsequent pregnancy outcomes.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy. OBJECTIVE: This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness. STUDY DESIGN: A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at <20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at <37 weeks of gestation and <34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of <5th or <10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at <37 weeks of gestation. RESULTS: Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at <37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at <37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at <34 weeks of gestation, any major congenital malformation, and size for gestational age of <5th or <10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features. CONCLUSION: There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

Hypertensive disorders of pregnancy and severe acute respiratory syndrome coronavirus-2 infection.

OBJECTIVES: We aimed to determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with an increased risk of hypertensive disorders of pregnancy (HDP). METHODS: A multicenter retrospective cohort study of all pregnant patients who had SARS-CoV-2 testing and delivered in a large health system between March 2020 and March 2021. Cases were stratified into two groups: patients who tested positive for SARS-CoV-2 during pregnancy vs. patients who tested negative. The primary outcome of HDP, defined as a composite of gestational hypertension, preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP Syndrome), and eclampsia by standard criteria, was compared between the two groups. Statistical analysis included multivariable logistic regression to adjust for potential confounders such as maternal demographics and comorbidities. Patient ZIP codes were linked to neighborhood-level data from the US Census Bureau's American Community Survey. RESULTS: Of the 22,438 patients included, 1,653 (7.4%) tested positive for SARS-CoV-2 infection. Baseline demographics such as age, body mass index, race, ethnicity, insurance type, neighborhood-built environmental and socioeconomic status, nulliparity, and pregestational diabetes differed significantly between the two groups. SARS-CoV- 2 infection in pregnancy was not associated with an increased risk of HDP compared to those without infection (14.9 vs. 14.8%; aOR 1.06 95% CI 0.90-1.24). CONCLUSIONS: In this large cohort that included a universally-tested population with several socioeconomic indicators, SARS-CoV-2 infection in pregnancy was not associated with an increased risk of HDP.

Atypical Presentation of Antenatal Eclampsia.

Most women who develop eclampsia have preceding preeclampsia (proteinuria and hypertension). This is especially true for otherwise healthy nulliparous women. However, recently, there has been a paradigm shift in this philosophy. There is mounting evidence that preeclampsia can develop even in the absence of proteinuria and hypertension and that eclampsia itself may be the initial manifestation of hypertensive disorder during pregnancy. We report a rare case of a 24-year-old primigravida at 30 weeks of gestation who presented with new-onset generalised tonic-clonic seizures without prior hypertension or proteinuria in her antenatal records. A thorough workup revealed this presentation to be the initial feature of atypical eclampsia. She was managed appropriately and discharged with an excellent outcome. This experience highlights some of the difficulties in managing a case of atypical eclampsia, namely, erratic onset and an unpredictable course, all of which interfere with timely diagnosis and treatment and contribute to maternal and fetal morbidity and mortality.

Differences and similarities in endothelial and angiogenic profiles of preeclampsia and COVID-19 in pregnancy.

BACKGROUND: COVID-19 presents a spectrum of signs and symptoms in pregnant women that might resemble preeclampsia. Differentiation between severe COVID-19 and preeclampsia is difficult in some cases. OBJECTIVE: To study biomarkers of endothelial damage, coagulation, innate immune response, and angiogenesis in preeclampsia and COVID-19 in pregnancy in addition to in vitro alterations in endothelial cells exposed to sera from pregnant women with preeclampsia and COVID-19. STUDY DESIGN: Plasma and sera samples were obtained from pregnant women with COVID-19 infection classified into mild (n=10) or severe (n=9) and from women with normotensive pregnancies as controls (n=10) and patients with preeclampsia (n=13). A panel of plasmatic biomarkers was assessed, including vascular cell adhesion molecule-1, soluble tumor necrosis factor-receptor I, heparan sulfate, von Willebrand factor antigen (activity and multimeric pattern), α2-antiplasmin, C5b9, neutrophil extracellular traps, placental growth factor, soluble fms-like tyrosine kinase-1, and angiopoietin 2. In addition, microvascular endothelial cells were exposed to patients' sera, and changes in the cell expression of intercellular adhesion molecule 1 on cell membranes and von Willebrand factor release to the extracellular matrix were evaluated through immunofluorescence. Changes in inflammation cell signaling pathways were also assessed by of p38 mitogen-activated protein kinase phosphorylation. Statistical analysis included univariate and multivariate methods. RESULTS: Biomarker profiles of patients with mild COVID-19 were similar to those of controls. Both preeclampsia and severe COVID-19 showed significant alterations in most circulating biomarkers with distinctive profiles. Whereas severe COVID-19 exhibited higher concentrations of vascular cell adhesion molecule-1, soluble tumor necrosis factor-α receptor I, heparan sulfate, von Willebrand factor antigen, and neutrophil extracellular traps, with a significant reduction of placental growth factor compared with controls, preeclampsia presented a marked increase in vascular cell adhesion molecule-1 and soluble tumor necrosis factor-α receptor I (significantly increased compared with controls and patients with severe COVID-19), with a striking reduction in von Willebrand factor antigen, von Willebrand factor activity, and α2-antiplasmin. As expected, reduced placental growth factor, increased soluble fms-like tyrosine kinase-1 and angiopoietin 2, and a very high soluble fms-like tyrosine kinase-1 to placental growth factor ratio were also observed in preeclampsia. In addition, a significant increase in C5b9 and neutrophil extracellular traps was also detected in preeclampsia compared with controls. Principal component analysis demonstrated a clear separation between patients with preeclampsia and the other groups (first and second components explained 42.2% and 13.5% of the variance), mainly differentiated by variables related to von Willebrand factor, soluble tumor necrosis factor-receptor I, heparan sulfate, and soluble fms-like tyrosine kinase-1. Von Willebrand factor multimeric analysis revealed the absence of von Willebrand factor high-molecular-weight multimers in preeclampsia (similar profile to von Willebrand disease type 2A), whereas in healthy pregnancies and COVID-19 patients, von Willebrand factor multimeric pattern was normal. Sera from both preeclampsia and severe COVID-19 patients induced an overexpression of intercellular adhesion molecule 1 and von Willebrand factor in endothelial cells in culture compared with controls. However, the effect of preeclampsia was less pronounced than the that of severe COVID-19. Immunoblots of lysates from endothelial cells exposed to mild and severe COVID-19 and preeclampsia sera showed an increase in p38 mitogen-activated protein kinase phosphorylation. Patients with severe COVID-19 and preeclampsia were statistically different from controls, suggesting that both severe COVID-19 and preeclampsia sera can activate inflammatory signaling pathways. CONCLUSION: Although similar in in vitro endothelial dysfunction, preeclampsia and severe COVID-19 exhibit distinctive profiles of circulating biomarkers related to endothelial damage, coagulopathy, and angiogenic imbalance that could aid in the differential diagnosis of these entities.

sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

OBJECTIVES: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. STUDY DESIGN: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio. RESULTS: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. CONCLUSIONS: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Frequent Placental SARS-CoV-2 in Patients with COVID-19-Associated Hypertensive Disorders of Pregnancy.

INTRODUCTION: Studies described an increased frequency of hypertensive disorders of pregnancy (HDP) after a COVID-19 episode. There is limited evidence about SARS-CoV-2 viral load in placenta. This study aimed to investigate the relationship between SARS-CoV-2 viral load in the placenta and clinical development of HDP after COVID-19 throughout different periods of gestation. METHODS: This is a case-control study in women with and without gestational hypertensive disorders after SARS-CoV-2 infection diagnosed by RT-PCR during pregnancy. Patients were matched by gestational age at the moment of COVID-19 diagnosis. We performed an analysis of SARS-CoV-2 RNA levels in placenta. RESULTS: A total of 28 women were enrolled. Sixteen patients were diagnosed with COVID-19 during the third trimester and the remaining 12 patients in the other trimesters. Ten placentas (35.7%) were positive for SARS-CoV-2, 9 of them (9/14, 64.3%) belonged to the HDP group versus 1 (1/14, 7.2%) in the control group (p = 0.009). Those cases with the highest loads of viral RNA developed severe preeclampsia (PE). CONCLUSION: Among women diagnosed with COVID-19 during pregnancy, the presence of SARS-CoV-2 in the placenta was more frequent among women suffering from PE or gestational hypertension. Furthermore, the most severe cases of HDP were associated with high placental viral load, not necessarily associated with a positive nasopharyngeal RT-PCR at delivery. Our data suggest that SARS-CoV-2 infection during pregnancy could trigger gestational hypertensive disorders through persistent placental infection and resulting placental damage.

What's New in Neuraxial Labor Analgesia.

PURPOSE OF REVIEW: This article provides an update of recent practice trends in neuraxial labor analgesia. It reviews available evidence regarding management of labor pain in obstetric patients with COVID-19, serious adverse events in obstetric anesthesia to help inform risk/benefit decisions, and increasingly popular neuraxial labor analgesia techniques and adjuvants. State-of-the-art modes of epidural drug delivery are also discussed. RECENT FINDINGS: There has recently been a focus on several considerations specific to obstetric anesthesia, such as anesthetic management of obstetric patients with COVID-19, platelet thresholds for the safe performance of neuraxial analgesia in obstetric patients with thrombocytopenia, and drug delivery modes for initiation and maintenance of neuraxial labor analgesia. SUMMARY: Neuraxial labor analgesia (via standard epidural, dural puncture epidural, and combined spinal epidural techniques) is the most effective therapy to alleviate the pain of childbirth. SARS-CoV-2 infection is not, in and of itself, a contraindication to neuraxial labor analgesia or cesarean delivery anesthesia. Early initiation of neuraxial labor analgesia in patients with COVID-19 is recommended if not otherwise contraindicated, as it may reduce the need for general anesthesia should emergency cesarean delivery become necessary. Consensus regarding platelet thresholds for safe initiation of neuraxial procedures has historically been lacking. Recent studies have concluded that the risk of spinal epidural hematoma formation after neuraxial procedures is likely low at or above an imprecise range of platelet count of 70-75,000 × 106/L. Thrombocytopenia has been reported in obstetric patients with COVID-19, but severe thrombocytopenia precluding initiation of neuraxial anesthesia is extremely rare. High neuraxial blockade has emerged as one of the most common serious complications of neuraxial analgesia and anesthesia in obstetric patients. Growing awareness of factors that contribute to failed conversion of epidural labor analgesia to cesarean delivery anesthesia may help avoid the risks associated with performance of repeat neuraxial techniques and induction of general anesthesia after failed epidural blockade. Dural puncture techniques to alleviate the pain of childbirth continue to become more popular, as do adjuvant drugs to enhance or prolong neuraxial analgesia. Novel techniques for epidural drug delivery have become more widely disseminated.

Coronavirus disease 2019 (COVID-19) and the risk of hypertensive disorders of pregnancy: a retrospective cohort study.

Objective: To evaluate of COVID-19 disease in pregnant women and its association with hypertensive disorders of pregnancy.Design: Retrospective Cohort StudySetting: Multicenter study from a large metropolitan hospital systemMethods: Patients who tested positive for COVID-19 during their pregnancy and delivered were compared to the three subsequent deliveries of patients who tested negative (controls). We evaluated the impact of COVID-19 on the development of hypertensive disorders of pregnancy.Results: Compared with pregnancies negative for SARs-CoV-2 infection, maternal SARs-CoV-2 infection was associated with an increased risk for hypertensive disorders of pregnancy (OR 3.68, 95% CI 1.67 - 8.10).Tweetable AbstractPatients who test positive for COVID-19 during their pregnancy are at increased risk of developing a hypertensive disorder of pregnancy. Earlier SARs-CoV-2 infection results in an increased risk of developing a hypertensive disorder.

SARS-CoV-2 infection during pregnancy and risk of preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: To examine the relationship between SARS-CoV-2 infection during pregnancy and the risk for preeclampsia. DATA SOURCES: MEDLINE, Embase, POPLINE, CINAHL, LILACS, and the World Health Organization COVID-19, Chinese, and preprint databases (all from December 1, 2019, to May 31, 2021). Google Scholar, bibliographies, and conference proceedings were also searched. STUDY ELIGIBILITY CRITERIA: Observational studies that assessed the association between SARS-CoV-2 infection during pregnancy and preeclampsia and that reported unadjusted and/or adjusted risk estimates and 95% confidence intervals or data to calculate them. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was preeclampsia. Secondary outcomes included preeclampsia with severe features, preeclampsia without severe features, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Two reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled unadjusted and adjusted odds ratios with 95% confidence intervals, and 95% prediction interval were calculated. Heterogeneity was quantified using the І2 statistic, for which І2≥30% indicated substantial heterogeneity. Subgroup and sensitivity analyses were performed to test the robustness of the overall findings. RESULTS: A total of 28 studies comprising 790,954 pregnant women, among which 15,524 were diagnosed with SARS-CoV-2 infection, met the inclusion criteria. The meta-analysis of unadjusted odds ratios showed that the odds of developing preeclampsia were significantly higher among pregnant women with SARS-CoV-2 infection than among those without SARS-CoV-2 infection (7.0% vs 4.8%; pooled odds ratio, 1.62; 95% confidence interval, 1.45-1.82; P<.00001; І2=17%; 26 studies; 95% prediction interval of the odds ratio, 1.28-2.05). The meta-analysis of adjusted odds ratios also showed that SARS-CoV-2 infection during pregnancy was associated with a significant increase in the odds of preeclampsia (pooled odds ratio, 1.58; 95% confidence interval, 1.39-1.80; P<.0001; І2=0%; 11 studies). There was a statistically significant increase in the odds of preeclampsia with severe features (odds ratio, 1.76; 95% confidence interval, 1.18-2.63; І2=58%; 7 studies), eclampsia (odds ratio, 1.97; 95% confidence interval, 1.01-3.84; І2=0%, 3 studies), and HELLP syndrome (odds ratio, 2.10; 95% confidence interval, 1.48-2.97; 1 study) among pregnant women with SARS-CoV-2 infection when compared to those without the infection. Overall, the direction and magnitude of the effect of SARS-CoV-2 infection during pregnancy on preeclampsia was consistent across most prespecified subgroup and sensitivity analyses. Both asymptomatic and symptomatic SARS-CoV-2 infections significantly increased the odds of developing preeclampsial; however, it was higher among patients with symptomatic illness (odds ratio, 2.11; 95% confidence interval, 1.59-2.81) than among those with asymptomatic illness (odds ratio, 1.59; 95% confidence interval, 1.21-2.10). CONCLUSION: SARS-CoV-2 during pregnancy is associated with higher odds of preeclampsia.