Severe Adverse Maternal Outcomes Research Articles

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia: A Stratified Analysis of the PARROT-2 Trial.

PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.

Plasma sFlt-1/PlGF ratio of 11.5 multiples of median predicts preeclampsia with severe features within two weeks of testing

BackgroundAngiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1 [sFlt-1]) and reduced angiogenic factors (VEGF and placental growth factor [PlGF]), contribute to the mechanisms of disease in preeclampsia. The ratio of sFlt-1 to PlGF has been used as a biomarker for preeclampsia, but cut-off values may vary with gestational age and assay platform. ObjectivesTo compare multiples of the median (MoM) of maternal plasma sFlt-1/PlGF ratio, sFlt-1, PlGF, and conventional clinical and laboratory values to predict preeclampsia with severe features. Study DesignWe conducted a cohort study across 18 U.S. centers involving hospitalized hypertensive individuals between 23-35 weeks' gestation. Receiver operating characteristic curve (ROC) analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. Their areas under the curve (AUC) were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within two weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birthweight <3rd percentile, very preterm birth [<32 weeks] and fetal/neonatal death). ResultsOut of 543 individuals included in the study, preeclampsia with severe features within two weeks was observed in 33.1% (n=180) of them. A ROC-derived cut-off of 11.5 MoM for sFlt-1/PlGF plasma ratio provided sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within two weeks. This cut-off was used to compare test positive cases (≥ cut-off) and test negative cases (< cut-off). Preeclampsia with severe features (66.0% vs. 5.7%; <0.001), and composites of severe adverse maternal (8.11% vs. 2.7%; p=0.006) or perinatal outcomes (41.3% vs. 10.14%; p=0.001) within two weeks were more frequent in test positive cases than test negative cases. sFlt-1/PlGF plasma ratio ≥11.5 MoM was independently associated with preeclampsia with severe features (adjusted incidence rate ratio [aIRR]: 9.08, 95% CI: 6.11 to 14.06; p<0.001) and a composite of severe adverse perinatal outcomes (aIRR: 9.42, 95% CI: 6.36 to 14.53; p<0.001), but not with a composite of severe adverse maternal outcomes (aIRR: 2.20, 95% CI: 0.95 to 5.54; p=0.08).The AUC of sFlt-1/PlGF plasma ratio in MoM (0.91; 95% CI: 0.89-0.94) for preeclampsia with severe features within two weeks was significantly higher (p<0.001 for all comparisons) than either plasma biomarker alone or any other parameter, with the exception of absolute sFlt-1/PlGF plasma ratio values. ConclusionsSFlt-1/PlGF plasma ratio ≥11.5 MoM among hospitalized, hypertensive patients between 23- and 35-week’s gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within two weeks.

External Validation of the fullPIERS Risk Prediction Model in a U.S. Cohort of Women With Preeclampsia [ID 2683408

INTRODUCTION: Hypertensive disorders of pregnancy are a leading cause of maternal morbidity and adverse pregnancy outcomes. The fullPIERS model was developed to predict severe adverse maternal outcomes within 48 hours of admission in patients with preeclampsia. This model has not been validated in the U.S. cohort. We sought to examine whether the fullPIERS model was predictive in the U.S. cohort. METHODS: This was a retrospective study of patients with preeclampsia who delivered at 23 weeks or greater from January 1, 2010, to December 31, 2020. Our primary outcome was a composite of maternal mortality or other serious complications of preeclampsia that occurred within 48 hours of admission. Using the prediction model that considers gestational age at admission, chest pain or dyspnea, serum creatinine, platelet, aspartate transaminase, and oxygen saturation, we calculated the probability of the composite outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic curve. Hosmer–Lemeshow test was used to assess the goodness-of-fit. RESULTS: Of 1,552 patients with preeclampsia, 77 (5.0%) had the composite outcome within 48 hours. The fullPIERS model had an AUC of 0.73 (95% CI, 0.66–0.80). However, the Hosmer–Lemeshow test showed poor calibration with a value of P&lt;.001. The calibration plot showed the model underestimated when the predicted probability was less than 10% and overestimated when the predicted probability was over 28%. CONCLUSION: The fullPIERS model had good AUC in the U.S. cohort of patients with preeclampsia but poor calibration. The fullPIERS model may not be clinically useful in the United States.

Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): a modelling study

Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia. We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of combined published data of 8843 patients from 11 low-income, middle-income, and high-income countries). Validation was undertaken on the unseen 25%, and an additional external validation was performed in 2901 inpatient women admitted with pre-eclampsia to two hospitals in south-east England. Predictive risk accuracy was determined by area-under-the-receiver-operator characteristic (AUROC), and risk categories were data-driven and defined by negative (-LR) and positive (+LR) likelihood ratios. Of 8843 participants, 590 (6·7%) developed the composite adverse maternal outcome within 2 days, 813 (9·2%) within 7 days, and 1083 (12·2%) at any time. An 18-variable random forest-based prediction model, PIERS-ML, was accurate (AUROC 0·80 [95% CI 0·76-0·84] vs the currently used logistic regression model, fullPIERS: AUROC 0·68 [0·63-0·74]) and categorised women into very low risk (-LR <0·1; eight [0·7%] of 1103 women), low risk (-LR 0·1 to 0·2; 321 [29·1%] women), moderate risk (-LR >0·2 and +LR <5·0; 676 [61·3%] women), high risk (+LR 5·0 to 10·0, 87 [7·9%] women), and very high risk (+LR >10·0; 11 [1·0%] women). Adverse maternal event rates were 0% for very low risk, 2% for low risk, 5% for moderate risk, 26% for high risk, and 91% for very high risk within 48 h. The 2901 women in the external validation dataset were accurately classified as being at very low risk (0% with outcomes), low risk (1%), moderate risk (4%), high risk (33%), or very high risk (67%). The PIERS-ML model improves identification of women with pre-eclampsia who are at lowest and greatest risk of severe adverse maternal outcomes within 2 days of assessment, and can support provision of accurate guidance to women, their families, and their maternity care providers. University of Strathclyde Diversity in Data Linkage Centre for Doctoral Training, the Fetal Medicine Foundation, The Canadian Institutes of Health Research, and the Bill & Melinda Gates Foundation.

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial

Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia. In this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420. Between Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator. Repeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. Tommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre.

Maternal Mortality in Women With Previable Premature Rupture of Membranes: An Analysis From the French Confidential Enquiry into Maternal Deaths

(Acta Obstet Gynecol Scand. 2022;101:1395–1402) Previable premature rupture of membranes (PvPROM) is a rare complication of pregnancy (&lt;1% frequency) but can lead to severe maternal adverse outcomes including sepsis and death. Conservative management without fetal extraction is common, but the documented risk of maternal sepsis remains elevated and variable even with prophylactic antibiotic treatment. The data on maternal mortality is lacking, and underreporting is a concern. The aim of this study was to characterize the lethality of PvPROM to inform decision-making as to whether to prolong a ruptured pregnancy or recommend termination.

State-Level Indicators of Structural Racism and Severe Adverse Maternal Outcomes During Childbirth.

Structural racism (SR) is viewed as a root cause of racial and ethnic disparities in maternal health outcomes. However, evidence linking SR to increased odds of severe adverse maternal outcomes (SAMO) is scant. This study assessed the association between state-level indicators of SR and SAMO during childbirth. Data for non-Hispanic Black and non-Hispanic white women came from the US Natality file, 2017-2018. The exposures were state-level Black-to-white inequity ratios for lower education level, unemployment, and prison incarceration. The outcome was patient-level SAMO, including eclampsia, blood transfusion, hysterectomy, or intensive care unit admission. Adjusted odds ratios (aORs) of SAMO associated with each ratio were estimated using multilevel models adjusting for patient, hospital, and state characteristics. A total of 4,804,488 birth certificates were analyzed, with 22.5% for Black women. SAMO incidence was 106.4 per 10,000 (95% CI 104.5, 108.4) for Black women, and 72.7 per 10,000 (95% CI 71.8, 73.6) for white women. Odds of SAMO increased 35% per 1-unit increase in the unemployment ratio for Black women (aOR 1.35; 95% CI 1.04, 1.73), and 16% for white women (aOR 1.16; 95% CI 1.01, 1.33). Odds of SAMO increased 6% per 1-unit increase in the incarceration ratio for Black women (aOR 1.06; 95% CI 1.03, 1.10), and 4% for white women (aOR 1.04; 95% CI 1.02, 1.06). No significant association was observed between SAMO and the lower education level ratio. State-level Black-to-white inequity ratios for unemployment and incarceration are associated with significantly increased odds of SAMO.

CRADLE-5: a stepped-wedge type 2 hybrid implementation-effectiveness cluster randomised controlled trial to evaluate the real-world scale-up of the CRADLE Vital Signs Alert intervention into routine maternity care in Sierra Leone—study protocol

BackgroundThe CRADLE Vital Signs Alert intervention (an accurate easy-to-use device that measures blood pressure and pulse with inbuilt traffic-light early warning system, and focused training package) was associated with reduced rates of eclampsia and maternal death when trialled in urban areas in Sierra Leone. Subsequently, implementation was successfully piloted as evidenced by measures of fidelity, feasibility and adoption. The CRADLE-5 trial will examine whether national scale-up, including in the most rural areas, will reduce a composite outcome of maternal and fetal mortality and maternal morbidity and will evaluate how the CRADLE package can be embedded sustainably into routine clinical pathways.MethodsCRADLE-5 is a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care across eight rural districts in Sierra Leone (Bonthe, Falaba, Karene, Kailahun, Koinadugu, Kono, Moyamba, Tonkolili). Each district will cross from control to intervention at six-weekly intervals over the course of 1 year (May 2022 to June 2023). All women identified as pregnant or within six-weeks postpartum presenting for maternity care in the district are included. Primary outcome data (composite rate of maternal death, stillbirth, eclampsia and emergency hysterectomy) will be collected. A mixed-methods process and scale-up evaluation (informed by Medical Research Council guidance for complex interventions and the World Health Organization ExpandNet tools) will explore implementation outcomes of fidelity, adoption, adaptation and scale-up outcomes of reach, maintenance, sustainability and integration. Mechanisms of change and contextual factors (barriers and facilitators) will be assessed. A concurrent cost-effectiveness analysis will be undertaken.DiscussionInternational guidance recommends that all pregnant and postpartum women have regular blood pressure assessment, and healthcare staff are adequately trained to respond to abnormalities. Clinical effectiveness to improve maternal and perinatal health in more rural areas, and ease of integration and sustainability of the CRADLE intervention at scale has yet to be investigated. This trial will explore whether national scale-up of the CRADLE intervention reduces maternal and fetal mortality and severe maternal adverse outcomes and understand the strategies for adoption, integration and sustainability in low-resource settings. If successful, the aim is to develop an adaptable, evidence-based scale-up roadmap to improve maternal and infant outcomes.Trial registrationISRCTN 94429427. Registered on 20 April 2022.

Major trauma in pregnancy: prediction of maternal and perinatal adverse outcomes

Trauma, largely the consequence of motor vehicle crashes, is the leading cause of pregnancy-associated maternal mortality. Prediction of adverse outcomes has been difficult in pregnancy given the infrequent occurrence of traumatic events and anatomic considerations unique to pregnancy. The injury severity score, an anatomic scoring system with weighting dependent on severity and anatomic region of injury, is used in the prediction of adverse outcomes in the nonpregnant population but has yet to be validated in pregnancy. This study aimed to estimate the associations between risk factors and adverse pregnancy outcomes after major trauma in pregnancy and to develop a clinical prediction model for adverse maternal and perinatal outcomes. This was a retrospective analysis of a cohort of pregnant patients who sustained major trauma and who were admitted to 1 of 2 level 1 trauma centers. Three composite adverse pregnancy outcomes were evaluated, namely adverse maternal outcomes and short- and long-term adverse perinatal outcomes, defined as outcomes occurring within the first 72 hours of the traumatic event or encompassing the entire pregnancy. Bivariate analyses were performed to estimate the associations between clinical or trauma-related variables and adverse pregnancy outcomes. Multivariable logistic regression analyses were performed to predict each adverse pregnancy outcome. The predictive performance of each model was estimated using receiver operating characteristic curve analyses. A total of 119 pregnant trauma patients were included, 26.1% of whom met the severe adverse maternal pregnancy outcome criteria, 29.4% of whom met the severe short-term adverse perinatal pregnancy outcome definition, and 51.3% of whom met the severe long-term adverse perinatal pregnancy outcome definition. Injury severity score and gestational age were associated with the composite short-term adverse perinatal pregnancy outcome with an adjusted odds ratio of 1.20 (95% confidence interval, 1.11-1.30). The injury severity score was solely predictive of the adverse maternal and long-term adverse perinatal pregnancy outcomes with odds ratios of 1.65 (95% confidence interval, 1.31-2.09) and 1.14 (95% confidence interval, 1.07-1.23), respectively. An injury severity score ≥8 was the best cutoff for predicting adverse maternal outcomes with 96.8% sensitivity and 92.0% specificity (area under the receiver operating characteristic curve, 0.990±0.006). An injury severity score ≥3 was the best cutoff for the short-term adverse perinatal outcomes, which correlates with a 68.6% sensitivity and 65.1% specificity (area under the receiver operating characteristic curve, 0.755±0.055). An injury severity score ≥2 was the best cutoff for the long-term adverse perinatal outcomes, yielding a 68.3% sensitivity and 72.4% specificity (area under the receiver operating characteristic curve, 0.763±0.042). For pregnant trauma patients, an injury severity score of ≥8 was predictive of severe adverse maternal outcomes. Minor trauma in pregnancy, defined in this study as an injury severity score <2, was not associated with maternal or perinatal morbidity or mortality. These data can guide management decisions for pregnant patients who present after trauma.

Downregulated ETV4 inhibits the proliferation, migration, and invasion of trophoblast cells in preeclampsia.

Preeclampsia is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes, but the mechanisms underlying the development of preeclampsia are not fully understood. This study shows that ETV4 plays an essential role in the proliferation, invasion, and migration of trophoblast cells by regulating MMP-2 and MMP-9 and is involved in the pathogenesis of preeclampsia. Preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of PE are not fully understood. ETS Variant Transcription Factor 4 (ETV4) plays an important role in cell proliferation, migration, and invasion. In this study, we aimed to explore the potential function of ETV4 in placental trophoblast cells. We analyzed the expression and location of ETV4 in PE and uncomplicated placental tissues using RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence staining. The results showed that both the mRNA and protein levels of ETV4 were markedly decreased in PE placental tissues compared with placental tissues from women with uncomplicated pregnancies (P < 0.05). Then, the effects of ETV4 on HTR-8/SVneo and Bewo cell proliferation, migration, and invasion were evaluated by MTT, 5-ethynyl-2-deoxyuridine (EdU), wound healing, and Transwell assays, respectively. The results showed that ETV4 knockdown inhibited both HTR-8/SVneo and Bewo cell proliferation, migration, and invasion (P < 0.05). Conversely, overexpression of ETV4 promoted both HTR-8/SVneo and Bewo cell proliferation, migration, and invasion (P < 0.05). We then measured the expression of MMP-2 and MMP-9 in HTR8/SVneo cells. We found that ETV4 knockdown decreased the mRNA and protein expression of MMP-2 and MMP-9, while ETV4 overexpression increased MMP-2 and MMP-9 mRNA and protein expression (P < 0.05). In conclusion, ETV4 plays an essential role in the proliferation, invasion, and migration of trophoblast cells by regulating MMP-2 and MMP-9. Our findings provide novel insight into the mechanisms underlying the occurrence of PE.

Evaluation of Low-Dose Aspirin to Prevent Preeclampsia in Pregnant People with Chronic Hypertension.

Our objective was to evaluate if the use of low-dose aspirin (LDA) among pregnant individuals with chronic hypertension (CHTN) reduces the rate of superimposed preeclampsia or other adverse maternal and neonatal outcomes. Our study included single-center cohort of pregnant individuals with CHTN who had a live birth after 23 weeks' gestation, between 2013 and 2018. The primary exposure was the use of LDA in pregnancy and the primary outcome was superimposed preeclampsia. LDA use was also evaluated by the timing of initiation, before or after 16 weeks' gestation. Secondary outcomes included preeclampsia subtypes (e.g., preeclampsia with severe features, early-onset disease), as well as adverse maternal and neonatal outcomes. Differences were analyzed by χ 2, Fisher's exact, or t tests, with logistic regression to adjust for confounders. Of 11,825 deliveries during the study period, 494 (4.2%) occurred in women with CHTN. Among those with CHTN, 174 (35%) were prescribed LDA, most often 81 mg daily (173 out of 174, 99%). Baseline characteristics were similar between groups, but the history of preeclampsia was more common in those prescribed LDA. The rate of superimposed preeclampsia was no different among those with CHTN-prescribed LDA compared with those who were not (36% vs. 30%, p = 0.2), even when restricting the analysis to those prescribed LDA before 16 weeks' gestation (33 vs. 30%, p = 0.2). In addition, LDA did not lead to a reduction in the rate of preeclampsia with severe features, early-onset preeclampsia, or other adverse maternal outcomes. However, the composite rate of adverse neonatal outcomes was lower in LDA users versus nonusers (4.0 vs. 13%, p = 0.002), which persisted after multivariable adjustment (adjusted odds ratio: 0.28, 95% confidence interval: 0.12-0.67). Among pregnant individuals with CHTN, LDA did not decrease the rate of superimposed preeclampsia. Further studies are warranted to validate our observed reduction in adverse neonatal outcomes and to determine if aspirin is more beneficial at dosages greater than 81 mg daily. · Superimposed preeclampsia rates are the same regardless of LDA.. · Decreased rate of adverse neonatal outcomes is seen with LDA.. · No decrease in adverse maternal outcomes is seen with LDA..

Comparison of clinical features in antepartum and postpartum HELLP syndrome

Objective: To analyze the clinical features and pregnancy outcomes in antepartum and postpartum hemolysis, elevated live enzymes, and low platelet count syndrome(HELLP syndrome). Methods: A retrospective study was conducted to collect maternal and neonatal information of pre-eclampsia complicated with HELLP syndrome in Peking University First Hospital during the ten years from April 2009 to March 2019. A total of 83 pregnant women were included according to the Tennessee Classification System. They were then allocated into two groups based on the onset time of HELLP syndrome: antepartum HELLP syndrome group (n=70) and postpartum HELLP syndrome group (n=13). The clinical features, symptoms, laboratory biomarkers, and pregnancy outcomes were compared between the two groups. Results: Among the 83 pregnant women with HELLP syndrome, 70 occurred prenatally (84%, 70/83) and 13 occurred postpartum (16%, 13/83). The twin or triplet pregnancy rate in the postpartum HELLP syndrome group was significantly higher than that in the antepartum HELLP syndrome group [6/13 vs 6% (4/70), P=0.001]. The gestational weeks for HELLP onset and delivery in the postpartum HELLP syndrome group were significantly later than those in the antepartum HELLP syndrome group [(35.8±3.0) vs (31.5±5.2) weeks, P=0.025; (36.7±2.3) vs (32.2±5.0) weeks, P=0.002]. The incidence of early-onset pre-eclampsia in the antepartum HELLP syndrome group was significant higher than that in the postpartum HELLP syndrome group [64% (45/70) vs 2/13, P=0.002]. The quantitative of 24-hour proteinuria was significant higher in the antepartum HELLP syndrome group than that in the postpartum HELLP syndrome group [(4.8±5.1) vs (1.8±1.6) g, P=0.002]. But there were no statistical significances in the comparison of other laboratory test indexes (all P>0.05). There were no significant differences between the two groups in clinical symptoms, severe maternal complications, transfusion or adverse maternal outcomes (all P>0.05). Conclusions: Antepartum and postpartum HELLP syndrome have similar clinical symptoms and laboratory characteristics. Both antepartum and postpartum HELLP syndrome could lead to severe maternal complications, which should be paid special attention in clinical practice, especially to the postpartum HELLP syndrome.

Severe Adverse Maternal and Neonatal Outcomes in Adolescent Mother-Newborn Dyads: A Multicentre Study in Latin America.

To compare the risk of severe adverse maternal outcomes (SMO) and neonatal outcomes (SNO) and analyse their maternal correlates in adolescent mother-newborn and young mother-newborn dyads in secondary and tertiary care users in Latin America. We performed a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health database in 83 secondary and tertiary hospitals in seven countries in Latin America. We constructed a composite indicator of both SMO and SNO and estimated odds ratios (OR) comparing adolescent mothers (aged 12-19) with young mothers (aged 20-24). Our unit of analysis was the mother-newborn dyad. We found that the combination of SMO and SNO was three times more likely in adolescent mother as compared to young mother dyads (OR 3.56; 95% CI 1.67-7.59). SNO either alone or in combination with SMO were more likely in adolescents aged 12 to 16 than in young women (OR 1.27 and 4.87, respectively). Adolescent mothers and their newborns are at an increased risk of severe adverse outcomes during child birth and in the first week postpartum compared to young mother dyads, especially young adolescents. Focusing on the dyad as a whole may facilitate a step towards integrated care which maximizes the health benefits of both mother and newborn. Continued efforts are needed to improve health care and prevention initiatives directed towards adolescent women and their newborns in Latin America.

Associations Between Soluble fms‐Like Tyrosine Kinase‐1 and Placental Growth Factor and Disease Severity Among Women With Preterm Eclampsia and Preeclampsia

BackgroundThe angiogenic factors soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are postulated to be pathogenic disease drivers of preeclampsia. If true, then circulating levels should become more deranged with increasing disease severity.Methods and ResultsWe investigated the association between circulating sFlt‐1 and PlGF levels and severe adverse maternal outcomes among 348 women with preeclampsia. Compared with 125 women with preeclampsia without severe features, 25 women with preeclampsia and any of hemolysis, elevated liver enzymes, low platelet count syndrome, disseminated intravascular coagulation, or severe renal involvement had sFlt‐1 levels that were 2.63‐fold higher (95% CI, 1.81–3.82), sFlt‐1/PlGF levels that were 10.07‐fold higher (95% CI, 5.36–18.91) and PlGF levels that were 74% lower (adjusted fold change, 0.26 [95% CI, 0.18–0.39]). Compared with 125 women with preeclampsia without severe features, 37 with eclampsia had sFlt‐1 levels that were 2‐fold higher (2.02 [95% CI, 1.32–3.09]), sFlt‐1/PIGF levels that were 4.71‐fold higher (95% CI, 2.30–9.66) and PIGF levels that were 63% lower (0.43‐fold change [95% CI, 0.27–0.68]). Compared with those without severe features, preeclampsia with severe hypertension (n=146) was also associated with altered angiogenic levels (sFlt‐1, 1.71‐fold change [95% CI, 1.39–2.11]; sFlt/PlGF, 2.91 [95% CI, 2.04–4.15]; PlGF, 0.59 [95%CI 0.47–0.74]). We also found that sFlt‐1 and PlGF levels were altered by the number of maternal complications experienced.ConclusionsFurther angiogenic imbalance among women with preeclampsia is likely a pathogenic disease driver responsible for the life‐threatening maternal complications.

Nurse workforce diversity and reduced risk of severe adverse maternal outcomes

Racial and ethnic diversification of the physician and nurse workforce is recommended as a leverage point to address the impact of structural racism in maternal care, but empirical evidence supporting this recommendation is currently lacking. This study aimed to assess the association between state-level registered nurse workforce racial and ethnic diversity and severe adverse maternal outcomes during childbirth. This population-based cross-sectional study analyzed 2017 US birth certificate data. Severe adverse maternal outcomes included eclampsia, blood transfusion, hysterectomy, or intensive care unit admission. Proportions of minoritized racial and ethnic registered nurses in each state were abstracted from the American Community Survey (5-year estimate, 2013-2017). This proportion was categorized into 3 terciles, with the first tercile corresponding to the lowest proportion and the third tercile corresponding to the highest proportion. Crude and adjusted odds ratios and 95% confidence intervals of severe adverse maternal outcomes associated with terciles of the state proportion of minoritized racial and ethnic nurses were estimated using logistic regression models. Of the 3,668,813 birth certificates studied, 29,174 recorded severe adverse maternal outcomes (79.5 per 10,000; 95% confidence interval, 78.6-80.4). The mean state proportion of minoritized racial and ethnic nurses was 22.1%, ranging from 3.3% in Maine to 68.2% in Hawaii. For White mothers, the incidence of severe adverse outcomes was 85.3 per 10,000 for those who gave births in states in the first tercile of the proportion of minoritized racial and ethnic nurses and 53.9 per 10,000 for those who gave birth in states in the third tercile (risk difference, -31.4 per 10,000; 95% confidence interval, -34.4 to -28.5). It corresponds to a 37% decreased risk of severe adverse maternal outcomes associated with giving birth in a state in the third tercile (crude odds ratio, 0.63; 95% confidence interval, 0.60-0.66). A decreased risk of severe adverse maternal outcomes was observed for Black mothers (crude odds ratio, 0.65; 95% confidence interval, 0.61-0.70), Hispanic mothers (crude odds ratio, 0.51; 95% confidence interval, 0.48-0.54), and Asian and Pacific Islander mothers (crude odds ratio, 0.65; 95% confidence interval, 0.58-0.72) but not for Native American mothers (crude odds ratio, 0.89; 95% confidence interval, 0.72-1.09) or mothers with >1 race (crude odds ratio, 1.44; 95% confidence interval, 0.72-1.09). After adjustment for patients and hospital characteristics, giving birth in states in the third tercile was associated with a reduced risk of severe adverse outcomes as follows: 32% for White mothers (adjusted odds ratio, 0.68; 95% confidence interval, 0.59-0.77), 20% for Black mothers (adjusted odds ratio, 0.80; 95% confidence interval, 0.65-0.99), 31% for Hispanic mothers (adjusted odds ratio, 0.69; 95% confidence interval, 0.58-0.82), and 50% for Asian and Pacific Islander mothers (adjusted odds ratio, 0.50; 95% confidence interval, 0.38-0.65). The associations of the proportion of minoritized racial and ethnic nurses with the risk of severe adverse maternal outcomes were not statistically significant for Native American mothers and more than 1 race mothers. Results were similar when blood transfusion was excluded from the outcome measure. A diverse state registered nurse workforce was associated with a reduced risk of severe adverse maternal outcomes during childbirth.

Compliance with COVID-19 Preventive Measures and Associated Factors Among Women Attending Antenatal Care at Public Health Facilities of Debre Berhan Town, Ethiopia.

BackgroundCoronavirus disease-2019 (COVID-19) is a highly contagious and cause for the death of many people worldwide. Due to physiological immunosuppressive state and mechanical alteration, pregnant women are at a higher risk of severe illness and adverse maternal and fetal outcomes from COVID-19 than non-pregnant women. Compliance with the preventive measures is essential to control COVID-19 related consequences. Therefore, this study aimed to assess compliance with COVID-19 preventive measures among pregnant women attending antenatal care at public facilities of Debre Berhan town, Ethiopia.MethodsA facility-based cross-sectional study was conducted from May 1 to 30, 2021 among 402 pregnant mothers. Data were collected via a face-to-face interviewer-administered questionnaire. Then, entered into Epi-Data version 4.6 and exported to SPSS version 25 for data analysis. In multivariable logistic regression analysis, variables with p < 0.05 were declared as statistically significant and the strength of statistical association was measured by adjusted odds ratio (AOR) and 95% confidence interval (CI).ResultsOf the total 396 participants, 222 (56.1%) of women had a good compliance with COVID-19 preventive measures. Maternal age (25–34 years) [AOR: 1.926; 95% CI (1.084, 3.421)] and (≥35 years) [AOR: 3.018; 95% CI (1.53, 5.952)], husband educational status [AOR: 3.68; 95% CI (1.55, 8.737)], had current chronic disease [AOR: 2.516; 95% CI (1.297, 4.883)], and knowledge [AOR: 5.484; 95% CI (3.057, 9.838)] were significant predictors to have good compliance with COVID-19 preventive measures.ConclusionAlthough COVID-19 is a global and national agenda, compliance towards its preventive measures was not sufficient enough. Therefore, scale-up the community awareness via media campaign is crucial which will eventually improve compliance. Furthermore, those women who had no pre-existing chronic diseases and those in the young age group should be given special consideration.

Subsequent pregnancy outcomes after abdominal vs. laparoscopic myomectomy

Objective To determine whether abdominal (open) vs. laparoscopic myomectomy affects the obstetrical outcomes of subsequent pregnancies. Methods A retrospective cohort study was conducted at a tertiary university medical center. The study population included women who had a documented birth following a myomectomy at our institution between the years 1997 and 2018. The obstetrical characteristics and immediate perinatal outcomes of the subsequent pregnancy following open vs. laparoscopic myomectomy were collected and compared. Data were retrieved from patients’ medical records via the institutional computerized database. Cases that lacked detailed surgery and delivery reports were excluded. Data were analyzed using a chi-square test for categorical variables and one-way ANOVA for continuous variables. A p-value <.05 was considered statistically significant. Results During the study period, 57 women met the inclusion criteria, of whom 66.6% (38/57) had an open and 33.3% (19/57) had a laparoscopic myomectomy. Women who underwent an open myomectomy had a higher rate of cesarean birth than those in the laparoscopic group (89.5 vs. 42.1%, p < .001). No cases of severe maternal or perinatal complications, uterine ruptures, or placental abruptions were identified in either study group. No other significant differences were noted between the two types of myomectomy. Conclusion Open myomectomy is associated with a higher rate of cesarean delivery than laparoscopic. No severe adverse maternal or neonatal outcomes were detected in either study group.

Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E-cadherin in the placenta of patients with preeclampsia.

Early-onset preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of early-onset PE are not fully understood. Ribosomal protein L39 (RPL39) is a member of the S39E family of ribosomal proteins that plays an important role in stem cell self-renewal, cancer metastasis, and chemoresistance. In this study, we aimed to explore the potential function of RPL39 in placental trophoblast cells. We analyzed the expression of RPL39 in early-onset PE and normal placental tissues using real-time PCR, western blot analysis, and immunohistochemistry. The results showed that RPL39 was markedly downregulated in early-onset PE placental tissues. RPL39 knockdown inhibited trophoblast cell proliferation, migration, and invasion, as well as placental explant outgrowth. Flow cytometry analysis suggested that knockdown of RPL39 resulted in cell cycle arrest at the G0/G1 phase, but had no significant effect on cell apoptosis. We also found that RPL39 knockdown could alter cell morphology. We then measured the expression of the epithelial cell marker E-cadherin following knockdown of RPL39 in Bewo and HTR8/SVneo cells. RPL39 knockdown increased the expression of E-cadherin. Furthermore, E-cadherin expression was upregulated in placental explant outgrowth tissues transfected with RPL39 small interfering RNA. In conclusion, RPL39 plays an essential role in proliferation, invasion, and migration of trophoblast cells by targeting E-cadherin. Our findings provide novel insight into the mechanisms underlying the occurrence of early-onset PE.

316 Preeclampsia severity after spontaneous or IVF conception in women age 40 and over

Preeclampsia (PE) is more common in women who conceived by in vitro fertilization (IVF). However, it is unclear if PE severity is worse in IVF pregnancies as prior studies have not fully controlled for age and other confounding factors. We sought to determine if PE severity is worse in women age 40 and over with IVF compared to spontaneous conception. Cohort study of women age 40 and over, who had PE and delivered at our institution from 1/1/13 to 12/31/17. This cohort, chosen due to the high prevalence of IVF conception in women 40 and over, was identified using ICD-10 codes and chart validation. Exclusions were maternal age <40, fetal demise, and non-IVF fertility treatments. The primary exposure was IVF conception (vs. spontaneous) and the primary outcome was PE with severe features (vs. PE without severe features). Secondary outcomes included severe symptoms, laboratory measures, and adverse maternal outcomes (see footnote Table 2). Analyses by t-test, Chi-squared or Fisher’s exact test, and logistic regression (α=0.05). We identified 237 women age 40 and over with PE (mean 42±2 years); 138 (58%) conceived spontaneously and 99 (42%) conceived by IVF. Women with IVF pregnancy were more often older, nulliparous, White, with multifetal gestation and lower BMI (Table 1). Compared to women with spontaneous conception, those with IVF pregnancy were not more likely to have PE with severe features (90% vs. 82%, P=0.09) (Table 2). The odds of PE with severe features was not increased in IVF pregnancies even after adjustment for age, race, BMI, nulliparity and multifetal gestation (aOR 1.9, 95% CI 0.7-5.1). Adverse maternal outcomes were increased with IVF pregnancy (36% vs. 23%, P=0.03), but this was not significant after multivariable adjustment (aOR 0.64, 95% CI 0.3-1.4). In women 40 and over, IVF pregnancy was not independently associated with an increase in preeclampsia severity or adverse maternal outcomes. However, most women 40 and over had PE with severe features, suggesting that age may drive disease severity regardless of mode of conception.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The first SARS-CoV-2 wave among pregnant women in Italy: results from a prospective population-based study.

This study aimed to estimate the incidence of SARS-CoV-2 infection among pregnant women during the first pandemic wave in Italy, and to describe COVID-19 disease characteristics and maternal and perinatal outcomes. National population-based prospective cohort study collecting information on women with SARS-CoV-2 diagnosis, confirmed within 7 days from hospital admission. The national SARS-CoV-2 rate was 6.04 per 1,000 births (95% CI 5.62-6.49) among pregnant women and 7.54 (95% CI 7.47-7.61) among women in reproductive age. 72.1% of the cohort developed mild COVID-19 disease without pneumonia nor need for ventilatory support. Severe disease was significantly associated with women's previous comorbidities (OR 2.55; 95% CI 0.98-6.90), obesity (OR 4.76; 95% CI 1.79-12.66) and citizenship from High Migration Pressure Countries (OR 3.43; 95% CI 1.27-9.25). During the first pandemic wave in Italy, the SARS-CoV-2 rate among pregnant women was lower compared to that detected among women of reproductive age, and risks of severe COVID-19 disease and adverse maternal and perinatal outcomes were rare.