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.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

The impact of the Covid-19 pandemic on maternity services: A review of maternal and neonatal outcomes before, during and after the pandemic.

OBJECTIVE: To explore any apparent trends in maternal or neonatal outcomes during the Covid-19 pandemic by comparing the maternity outcomes before, during and after the pandemic. STUDY DESIGN: A retrospective review was performed of maternity statistics recorded on the hospital database of a large tertiary referral centre in Dublin with over 8000 deliveries per annum from 1st January to 31st July 2020. This time period represented the months prior to, during the peak and following the pandemic in Ireland. RESULTS: There was no correlation between the monthly number of Covid deaths and the monthly number of perinatal deaths (r = 0.465, NS), preterm births (r = 0.339, NS) or hypertensive pregnancies (r = 0.48, NS). Compared to the combined numbers for the same month in 2018 and 2019, there were no significant changes in perinatal deaths or preterm births in the months when Covid deaths were at their height. The rate of preterm birth was significantly less common in January-July 2020 compared to January-July in 2018/2019 (7.4 % v 8.6 %, chi-sq 4.53, P = 0.03). CONCLUSION: The was no evidence of a negative impact of the Covid-19 pandemic on maternity services, as demonstrated by maternal and neonatal outcomes.

HSV infection is associated with gestational hypertension: results from the US National inpatient sample.

The purpose of this study was to determine if there is an association between maternal herpes simplex virus (HSV) infection and pre-eclampsia/eclampsia or gestational hypertension. The US Nationwide Inpatient Sample database was searched for women aged 15-44 years who delivered in a hospital between 2005 and 2014. The patients were categorized into those with and without HSV and pre-eclampsia/eclampsia and gestational hypertension were compared between the groups. The analytic sample size (n=8 264 076) was equivalent to a population-based sample size of 40 653 030 patients. After adjusting for significant variables including age, race, income, insurance status, diabetes mellitus (DM), gestational DM, obesity, and multiple gestations, multivariate regression analysis indicated that HSV was associated with a higher OR for gestational hypertension (adjusted OR 1.038; 95% CI 1.004 to 1.072). However, HSV was not associated with pre-eclampsia/eclampsia (OR 1.001; 95% CI 0.968 to 1.035) in univariate regression analysis. The results of the current study suggest that HSV infection is associated with gestational hypertension but not pre-eclampsia. Given the prevalence of HSV infection and its potential association with hypertensive disorders of pregnancy, further study of HSV and hypertension in pregnancy is warranted.

Evaluation of Human Papillomavirus as a Risk Factor for Preterm Birth or Pregnancy-Related Hypertension.

OBJECTIVE: To compare rates of preterm birth and pregnancy-related hypertension in women with and without human papillomavirus (HPV) infection. METHODS: We performed a retrospective cohort study of all women delivered at our institution in 2013 who had cervical cancer screening test results within 3 years before delivery. Patients were excluded if they had prior procedure(s) for cervical dysplasia other than biopsy. There were two primary outcomes: preterm birth (less than 37 weeks of gestation) and pregnancy-related hypertension (gestational hypertension, preeclampsia, or eclampsia). Multivariable logistic regression was performed to adjust for confounders including demographic variables, diabetes, prior preterm birth, chronic hypertension, and other genital infections. Assuming a 10% prevalence of HPV, a rate of 12% in the HPV-negative group for both preterm birth and pregnancy-related hypertension, α of 0.05, and ß of 0.2, we needed 2,207 patients to detect a 60% increase in the rate of either outcome in the HPV-positive group. RESULTS: A total of 3,958 patients delivered in 2013, of whom 2,321 met eligibility criteria, 242 (10.4%) of whom were HPV-positive and 2,079 (89.2%) of whom were HPV-negative. In multivariate analyses, the rate of preterm birth was not significantly different between HPV-positive and HPV-negative women (16.5% compared with 12.2%, adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 0.9-1.9); rates of pregnancy-related hypertension also were not significantly different between HPV-positive and HPV-negative women (17.0% compared with 16.4%, adjusted OR 1.0, 95% CI 0.7-1.5). CONCLUSION: Maternal HPV infection is not an independent risk factor for preterm birth or pregnancy-related hypertension.

Fetal exposure to herpesviruses may be associated with pregnancy-induced hypertensive disorders and preterm birth in a Caucasian population.

OBJECTIVE: To investigate the role of fetal viral infection in the development of a range of adverse pregnancy outcomes (APOs), including pregnancy-induced hypertensive disorders (PIHD), antepartum haemorrhage (APH), birthweight <10th percentile (small for gestational age, SGA) and preterm birth (PTB). DESIGN: Population-based case-control study. SETTING: Laboratory-based study. POPULATION: The newborn screening cards of 717 adverse pregnancy cases and 609 controls. METHODS: Newborn screening cards were tested for RNA from enteroviruses and DNA from herpesviruses using polymerase chain reaction (PCR). The herpesviruses were detected using two PCRs, one detecting nucleic acids from herpes simplex virus (HSV)-1, HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus (HHV)-8, hereafter designated Herpes PCR group A viruses, and the other detecting nucleic acids from varicella-zoster virus (VZV), HHV-6 and HHV-7, hereafter designated Herpes PCR group B viruses. MAIN OUTCOME MEASURE: Odds ratios and 95% CIs for specific APOs. RESULTS: For both term and PTBs, the risk of developing PIHD was increased in the presence of DNA from Herpes PCR group B viruses (OR 3.57, 95% CI 1.10-11.70), CMV (OR 3.89, 95% CI 1.67-9.06), any herpesvirus (OR 5.70, 95% CI 1.85-17.57) and any virus (OR 5.17, 95% CI 1.68-15.94). The presence of CMV was associated with PTB (OR 1.61, 95% CI 1.14-2.27). No significant association was observed between SGA or APH and exposure to viral infection. CONCLUSIONS: Fetal exposure to herpesvirus infection was associated with PIHD for both term and PTBs in this exploratory study. Exposure to CMV may also be associated with PTB. These findings need confirmation in future studies.