Severe Adverse Perinatal Outcomes Research Articles

Unisex and Sex-Specific Prescriptive Fetal Growth Charts for Improved Detection of Small-for-Gestational-Age Babies in a Low-Risk Population: A post hoc Analysis of a Cluster-Randomized Study.

Our aim was to develop and evaluate the performance of population-based sex-specific and unisex prescriptive fetal abdominal circumference growth charts in predicting small-for-gestational-age (SGA) birthweight, severe SGA (sSGA) birthweight, and severe adverse perinatal outcomes (SAPO) in a low-risk population. This is a post hoc analysis of the Dutch nationwide cluster-randomized IRIS study, encompassing ultrasound data of 7,704 low-risk women. IRIS prescriptive unisex and IRIS sex-specific abdominal circumference (AC) fetal growth charts were derived using quantile regression. As a comparison, we used the descriptive unisex Verburg chart, which is commonly applied in the Netherlands. Diagnostic parameters were calculated based on the 34-36 weeks' ultrasound. Sensitivity rates for predicting SGA and sSGA birthweights were more than twofold higher based on the IRIS prescriptive sex-specific (respectively SGA 43%; sSGA 59%) and unisex (SGA 39%; sSGA 55%) charts, compared to the Verburg chart (SGA 16%; sSGA 23% both p < 0.01). Specificity rates were highest for Verburg (SGA 99%; sSGA 98%) and lowest for IRIS sex-specific (SGA 94%; sSGA 92%). Results for predicting SGA with SAPO were similar for the prescriptive charts (44%), and again higher than the Verburg chart (20%). The IRIS sex-specific chart identified significantly more males as SGA and sSGA (respectively, 42%; 60%, p < 0.001) than the IRIS unisex chart (respectively, 35%; 53% p < 0.01). Our study demonstrates improved performance of both the IRIS sex-specific and unisex prescriptive fetal growth compared to the Verburg descriptive chart, doubling detection rates of SGA, sSGA, and SGA with SAPO. Additionally, the sex-specific chart outperformed the unisex chart in detecting SGA and sSGA. Our findings suggest the potential benefits of using prescriptive AC fetal growth charts in low-risk populations and emphasize the importance of considering customizing fetal growth charts for sex. Nevertheless, the increased sensitivity of these charts should be weighed against the decrease in specificity.

Research protocol - Evaluating data quality in the Netherlands Perinatal Registry (Perined): A data comparison study using hospital records from the IUGR Risk Selection (IRIS) study

Background The quality of registry based studies depends largely on the data accuracy of the registries. The Dutch Perinatal Registry (Perined) is a nationwide database comprising perinatal data digitally provided by different healthcare providers. Perined data are used for comparing outcomes across regions and healthcare institutions as well as for quality analyses and research purposes. However, little is known about the data quality of the Perined database. Therefore, the aim of this study is to assess the quality of Perined data compared to hospital records and case report forms (CRFs) that were part of the IUGR Risk Selection (IRIS) study. Methods In this comparison study data from Perined and the IRIS Study will be used. The IRIS study was a large cluster-randomized trial investigating the effectiveness of routine third trimester ultrasonography in reducing severe adverse perinatal outcomes among Dutch low-risk pregnant women. A subsample of the IRIS study of neonates being at risk of severe adverse perinatal outcomes and their mothers will be used. Baseline demographic data were collected by midwives from participating women at inclusion (around 22 weeks’ gestation) using CRFs, and in-depth neonatal and maternal clinical data were retrieved from hospital records by trained research assistants. These latter IRIS study data were linked and compared to Perined data. Completeness of Perined data will be calculated for every variable. The reliability will be assessed as the percent of agreement between Perined and hospital record data or the CRF-based data. Additionally, intra-class correlation coefficients will be calculated for continuous variables, and Kappa and ‘Prevalence-and-Bias-Adjusted Kappa’ will be calculated for categorical variables. Discussion The results of the proposed comparison study will provide users of Perined data insight in its data quality. This will serve as an example of the accuracy of registry based data used in maternal and neonatal care research.

Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 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.

Visceral Leishmaniasis in a Twin Pregnancy: A Case Report and Review of the Literature.

Visceral leishmaniasis (VL), often referred to as kala-azar, is quite rare in developed countries during pregnancy. Only few studies have evaluated its impact on perinatal outcome. It is caused primarily by Leishmania donovani or Leishmania infantum and presents with a wide spectrum of clinical manifestations from cutaneous ulcers to multisystem disease. Differential diagnosis is challenging as symptoms and signs are insidious, mimicking other diseases. Misdiagnosis can result in severe adverse perinatal outcomes, even maternal/neonatal death. Early treatment with liposomal amphotericin-B (LAmB) is currently the first choice with adequate effectiveness. We report a rare case of VL in a twin pregnancy with onset at the second trimester, presenting with periodic fever with rigors, right flank pain, and gradual dysregulation of all three cell lines. The positive rK39 enzyme-linked immunosorbent assay test confirmed the diagnosis. Treatment with LAmB resulted in clinical improvement within 48 h and in the delivery of two late-preterm healthy neonates with no symptoms or signs of vertical transmission. The one-year follow-up, of the mother and the neonates, was negative for recurrence. To our knowledge, this is the first reported case of VL in a twin pregnancy, and consequently treatment and perinatal outcome are of great importance.

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study

BackgroundThe aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. MethodsThis was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000–2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests.Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. FindingsThe final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0·19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13·2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0·74%), with the highest rate (19·6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7·59% livebirths), with the peak incidence occurring in the <1st centile category (12·3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10–90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. InterpretationAlthough the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently “appropriately grown” (i.e., birthweight 10th - 90th centile). FundingNational Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women’s Health Foundation – Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

Abnormal Shape and Size of the Cardiac Ventricles Are Associated with a Higher Risk of Neonatal Death in Fetuses with Isolated Left Congenital Diaphragmatic Hernia

Introduction: The objective of this study was to evaluate the association between fetal cardiac deformation analysis (CDA) and cardiac function with severe adverse perinatal outcomes in fetuses with isolated left congenital diaphragmatic hernia (CDH). Methods: CDA in each ventricle (contractility, size, and shape), evaluated by speckle tracking and novel FetalHQ software, and markers of cardiac function (E/A ratios, pulmonary and aortic peak systolic velocities, and sigmoid annular valve diameters), were evaluated in fetuses with isolated left CDH. Two evaluations were performed: at referral (CDA and function) and within 3 weeks of delivery (CDA). Severe adverse neonatal outcomes were considered neonatal death (ND) or survival with CDH-associated pulmonary hypertension (CDH-PH). Differences and associations between CDA, cardiac function, and severe adverse outcomes were estimated. Results: Fifty fetuses were included, and seventeen (34%) had severe adverse neonatal outcomes (11 ND and 6 survivors with CDH-PH). At first evaluation, the prevalence of a small left ventricle was 34% (17/50) with a higher prevalence among neonates presenting severe adverse outcomes (58.8 [10/17] vs. 21.2% [7/33]; p = 0.01; OR, 5.03 [1.4–19.1; p = 0.01]) and among those presenting with neonatal mortality (8/11 [72.7] vs. 9/39 [23.0%]; p = 0.03; OR, 8.9 [1.9–40.7; p = 0.005]). No differences in cardiac function or strain were noted between fetuses with or without severe adverse outcomes. Within 3 weeks of delivery, the prevalence of small left ventricle was higher (19/34; 55.8%) with a more globular shape (reduced transverse/longitudinal ratio). A globular right ventricle was significantly associated with ND or survival with CDH-PH (OR, 14.2 [1.5–138.3]; p = 0.02). Conclusion: Fetuses with isolated CDH at risk of perinatal death or survival with CDH-PH had a higher prevalence of a small left ventricle and abnormal shape of the right ventricle.

Perinatal outcome of fetuses predicted to be large-for-gestational age on universal third-trimester ultrasound in non-diabetic pregnancy.

To describe the perinatal outcome of fetuses predicted to be large-for-gestational age (LGA) on universal third-trimester ultrasound in non-diabetic pregnancies of women attempting vaginal delivery. This was a prospective population-based cohort study of patients from a single tertiary maternity unit in the UK offering universal third-trimester ultrasound and practicing expectant management of suspected LGA until 41-42 weeks. All women with a singleton pregnancy and an estimated due date between January 2014 and September 2019 were included. Women delivering before 37 weeks, those having a planned Cesarean delivery, those with pre-existing or gestational diabetes, those with fetal abnormalities and those who did not undergo a third-trimester scan were excluded from the assessment of perinatal outcome of cases with LGA predicted on ultrasound after implementation of the universal scan period. Association of LGA on universal third-trimester ultrasound screening and perinatal adverse outcome was assessed, with the exposures of interest being estimated fetal weight (EFW) at the 90th -95th , > 95th and > 99th percentile. The reference group was composed of fetuses with EFW at the 30th -70th percentile. Analysis was performed using multivariate logistic regression. The evaluated adverse perinatal outcomes included a composite outcome of admission to neonatal intensive care unit, Apgar score < 7 at 5 min and arterial cord pH < 7.1 (CAO1) and a composite outcome of stillbirth, neonatal death and hypoxic ischemic encephalopathy (CAO2). Secondary maternal outcomes were induction of labor, mode of delivery, postpartum hemorrhage, shoulder dystocia and obstetric anal sphincter injury. Cases with EFW > 95th percentile on universal third-trimester scan were at increased risk of CAO1 (adjusted odds ratio (aOR), 2.18 (95% CI, 1.69-2.80)) and CAO2 (aOR, 2.58 (95% CI, 1.05-6.34)). Cases with EFW at the 90th -95th percentile had a less pronounced increase in the risk of CAO1 (aOR, 1.35 (95% CI, 1.02-1.78)) and were not at increased risk of CAO2. All pregnancies with a fetus predicted to be LGA were at increased risk of all of the evaluated secondary maternal outcomes except for obstetric anal sphincter injury. The risk of adverse maternal outcome was typically higher with increasing EFW. Post-hoc exploration of data suggested that shoulder dystocia had a limited contribution to composite adverse perinatal outcomes in LGA cases (population attributable fraction of 10.8% for CAO1 and 29.1% for CAO2). Cases with EFW > 95th percentile are at increased risk of severe adverse perinatal outcome, such as death and hypoxic ischemic encephalopathy. These findings should aid antenatal counseling regarding the associated risk and delivery options. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study.

The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks'gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal Outcomes at Birth in Women Infected and Non-Infected with SARS-CoV-2: A Retrospective Study

Background: Coronavirus disease 2019 (COVID-19) was declared as a pandemic and public health emergency on 11 March 2020 by the World Health Organization. Different clinical trials on the efficacy of mRNA vaccination have excluded pregnant women, leading to a lack of empirical evidence on the efficacy of the vaccine in this population. The aim of the study was to examine the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at birth and adverse perinatal outcomes in infected and non-infected women from a university hospital in Spain. Methods: The data were obtained from electronic health records from 1 March 2020 to 28 February 2022. A bivariate descriptive analysis was performed, comparing women with and without confirmed SARS-CoV-2 infection during pregnancy using the chi-square test. A multivariate logistic regression was complementarily conducted to determine whether SARS-CoV-2 infection increases the risk of adverse obstetric and perinatal outcomes. Results: A total of 2676 women were divided into two groups: non-infected with SARS-CoV-2 (n = 2624) and infected with SARS-CoV-2 (n = 52). Infected women were primarily multiparous (p &lt; 0.03) and had received an incomplete vaccination regimen (p &lt; 0.001). A greater incidence of premature rupture of membranes (p &lt; 0.04) was observed among the non-infected women. Pertaining to perinatal outcomes, there was a notable rise in NICU admissions (p &lt; 0.014), coupled with an extended duration of stay (p &lt; 0.04), for neonates born to infected mothers in comparison to their non-infected counterparts. Conclusion: Although SARS-CoV-2 infection may pose significant risks to pregnant women and their infants, adverse obstetrical/puerperal outcomes do not significantly differ between women infected and non-infected to SARS-CoV-2 in our study. NICU admissions were higher for neonates born to infected mothers. Additionally, coronavirus disease 2019 vaccination during pregnancy is not associated with severe adverse perinatal outcomes.

Importance of antenatal identification of small for gestational age fetuses on perinatal and childhood outcomes: A register-based cohort study.

Fetal growth restriction (FGR) is associated with increased risk for stillbirth, perinatal morbidity, cerebral palsy, neurodevelopmental disorders and cardiovascular disease later in life. Identifying small-for-gestational-age (SGA) fetuses is crucial for the diagnosis of FGR. The aim of this study was to investigate the association between antenatal identification of SGA fetuses and severe adverse perinatal and childhood outcome. A register-based cohort study of all newborns delivered in Stockholm in 2014 and 2017. singleton pregnancies without chromosomal aberrations or structural abnormalities, with a gestational age at delivery between 22+0 and 43+0 (n = 48 843). Data from childbirth records were linked to data from nationwide Swedish registers. Pregnancy including offspring data were reviewed. Adverse outcomes for non-identified and identified SGA newborns were compared using logistic regression models. Primary outcome was a composite outcome called severe adverse outcome, defined as at least one of the following: stillbirth, severe newborn distress (Apgar score <4 at 5 min, pH <7 or resuscitation activities >10 min), severe neonatal outcome (hypoxic ischemic encephalopathy 2-3, necrotizing enterocolitis, neonatal seizures, intraventricular hemorrhage grade 3-4, bronchopulmonary disease or death at <1 year), severe childhood outcome (cognitive impairment or motor impairment or cerebral palsy or hearing impairment or visual impairment or death at 1-3 years old). Secondary outcomes were stillbirth, severe newborn distress, severe neonatal outcome, severe childhood outcome. No association was found between antenatal identification of SGA fetuses and severe adverse outcome using the complete composite outcome (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.93-1.53). In subgroup analyses, non-identified SGA fetuses had an almost fivefold increased risk for stillbirth (aOR 4.79, 95% CI 2.63-8.72) and an increased risk for severe newborn distress (aOR 1.36, 95% CI 1.02-1.82), but a decreased risk for severe childhood outcome (aOR 0.63, 95% CI 0.40-0.99). No association was found between antenatal identification of SGA and severe neonatal outcome. Non-identified SGA fetuses have an increased risk for stillbirth and severe newborn distress. Conversely, identified SGA fetuses have an increased risk for severe childhood outcome.

Factors related to COVID-19 vaccination intention and uptake among childbearing women.

Pregnant women are a vulnerable population for coronavirus disease 2019 (COVID-19) due to their risk for severe symptoms and adverse perinatal outcomes. Our objective was to identify contributors to COVID-19 vaccine intention in pregnancy and subsequent uptake, informed by the Theory of Planned Behavior, the Health Belief Model, and paradigms implicating social determinants of health (SDoH). Total of 1,899 pregnant women across the United States completed questionnaires in December 2020 (T1) and April 2021 (T2). A structural equation model (SEM) was built from hypothesized contributors to vaccine intention (T1) and uptake (T2), including perceived threat of COVID-19, attitudes toward infection mitigation behaviors, and social determinants of health SDoH (i.e., socioeconomic status [SES], minoritized identity), controlling for maternal health, age, and county-level political orientation. In the SEM, SDoH variables, perceived threat and behavioral attitudes predicted vaccine intention. SDoH were directly associated with vaccine uptake and indirectly associated via vaccine intention (SES direct effect b = .17, total effect b = .38; identifying as Black/African American direct effect b = -.05, total effect b = -.09) The SEM demonstrated good fit and explained 38% of the variance in vaccine intention and 26% in vaccine uptake. COVID-19 vaccination for pregnant women is influenced by SDoH and perceptual factors. Particular attention should focus on persons with lower SES and Black/African American women who reported lower vaccination intention and uptake. Potential routes to increase vaccination in perinatal populations include reducing accessibility barriers and providing information about vaccine safety and efficacy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Cost-effectiveness analysis of induction of labour at 41 weeks and expectant management until 42 weeks in low risk women (INDEX trial).

To assess the cost-effectiveness of elective induction of labour (IOL) at 41 weeks and expectant management (EM) until 42 weeks. Cost-effectiveness analysis from a healthcare perspective alongside a randomised controlled trial (INDEX). 123 primary care midwifery practices and 45 obstetric departments of hospitals in the Netherlands. We studied 1801 low-risk women with late-term pregnancy, randomised to IOL at 41 weeks (N=900) or EM until 42 weeks (N=901). The incremental cost-effectiveness ratio (ICER) was expressed as the ratio of the difference in costs and the difference in main perinatal outcomes. A Cost-Effectiveness Acceptability Curve (CEAC) was constructed to assess whether induction is cost-effective for a range of monetary values as thresholds. We performed subgroup analysis for parity. Direct medical costs, composite adverse perinatal outcome (CAPO) (perinatal mortality, NICU admission, Apgar 5min < 7, plexus brachialis injury and/or meconium aspiration syndrome) and composite severe adverse perinatal outcome (SAPO) (including Apgar 5min < 4 instead of < 7). The average costs were €3858 in the induction group and €3723 in the expectant group (mean difference €135; 95 % CI -235 to 493). The ICERs of IOL compared to EM to prevent one additional CAPO and SAPO was €9436 and €14,994, respectively. The CEAC showed a 80 % chance of IOL being cost-effective with a willingness-to-pay of €22,000 for prevention of one CAPO and €50,000 for one SAPO. Subgroup analysis showed a willingness-to-pay to prevent one CAPO for nulliparous of €47,000 and for multiparous €190,000. To prevent one SAPO the willingness-to-pay is €62,000 for nulliparous and €970,000 for multiparous women. Induction at 41 weeks has an 80 % chance of being cost-effective at a willingness-to-pay of €22,000 for prevention of one CAPO and €50,000 for prevention of one SAPO. Subgroup analysis suggests that induction could be cost-effective for nulliparous women while it is unlikely cost-effective for multiparous women.Cost-effectiveness in other settings will depend on baseline characteristics of the population and health system organisation and funding.

A Review of Cardiovascular Complications among Pregnant Patients with COVID-19.

Cardiovascular complications of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection are well-described in the general population but remain limited among pregnant patients. This review summarizes data from case reports, case series, and observational studies of cardiovascular manifestations of corona virus disease 2019 (COVID-19) in pregnant patients and provides recommendations to the cardiovascular clinician regarding management considerations in this vulnerable population. Pregna is an immunocompromised state in which cardiovascular demands are increased. Cardiovascular complications of COVID-19 that have been described in pregnancy include myocardial injury, cardiomyopathy, thromboembolism, pre-eclampsia and arrhythmia. Physiologic and cardiovascular changes in pregnancy predispose pregnant patients with COVID-19 to more severe illness than the general population. Black or Hispanic race, obesity, diabetes, hypertension and lung disease are risk factors for more severe infection, maternal death and adverse perinatal outcomes. Pregnant patients with severe COVID-19 disease compared with non-pregnant age-matched women with COVID infection are more likely to be admitted to the intensive care unit (ICU), receive mechanical ventilation and require advanced mechanical circulatory support. Cardiovascular complications of COVID-19 in pregnant patients requires further attention, particularly given the anticipated increase in birth volume and ongoing nature of COVID-19 pandemic with novel variants. Clinicians should have a lower threshold for cardiac testing and multidisciplinary management in pregnant women with severe COVID-19 disease. Given the persistence of COVID-19 within our communities, diagnostic laboratory and imaging testing for high-risk pregnant patients hospitalized with COVID-19 infection should be routine. We strongly urge the implementation of a cardio-obstetric multidisciplinary team in individually managing these high-risk patients in an effort to improve maternal and fetal outcomes.

Elective induction of labour and expectant management in late-term pregnancy: A prospective cohort study alongside the INDEX randomised controlled trial.

ObjectiveTo assess adverse perinatal outcomes and caesarean section of low-risk women receiving elective induction of labour at 41 weeks or expectant management until 42 weeks according to their preferred and actual management strategy.DesignMulticentre prospective cohort study alongside RCT.Setting90 midwifery practices and 12 hospitals in the Netherlands.Population3642 low-risk women with uncomplicated singleton late-term pregnancy.Main outcome measuresComposite adverse outcome (perinatal death, Apgar score 5′ < 7, NICU admission, meconium aspiration syndrome), composite severe adverse perinatal outcome (all above with Apgar score 5′ < 4 instead of < 7) and caesarean section.ResultsFrom 2012–2016, 3642 women out of 6088 eligible women for the INDEX RCT, participated in the cohort study for observational data collection (induction of labour n = 372; expectant management n = 2174; unknown preference/management strategy n = 1096).Adverse perinatal outcome occurred in 1.1 % (4/372) in the induction group versus 1.9 % (42/2174) in the expectant group (adjRR 0.56; 95 %CI: 0.17–1.79), with severe adverse perinatal outcome occurring in 0.3 % (1/372) versus 1.0 % (22/2174), respectively (adjRR 0.39; 95 % CI: 0.05–2.88). There were no stillbirths among all 3642 women; one neonatal death occurred in the unknown preference/management group. Caesarean section rates were 10.5 % (39/372) after induction and 8.9 % (193/2174) after expectant management (adjRR 1.32; 95 % CI: 0.95–1.84).A higher incidence of adverse perinatal outcome was observed in nulliparous compared to multiparous women. Nulliparous 1.8 % (3/170) in the induction group versus 2.6 % (30/1134) in the expectant management group (adjRR 0.58; 95 % CI 0.14–2.41), multiparous 0.5 % (1/201) versus 1.1 % (11/1039) (adjRR 0.54; 95 % CI 0.07–24.19). One maternal death due to amniotic fluid embolism occurred after elective induction at 41 weeks + 6 days.ConclusionIn this cohort study among low-risk women receiving the policy of their preference in late-term pregnancy, a non-significant difference was found between induction of labour at 41 weeks and expectant management until 42 weeks in absolute risks of composite adverse (1.1 % versus 1.9 %) and severe adverse (0.3 % versus 1.0 %) perinatal outcome. The risks in this cohort study were lower than in the trial setting. There were no stillbirths among all 3642 women. Caesarean section rates were comparable.

Severe smallness as predictor of adverse perinatal outcome in suspected late small-for-gestational-age fetuses: systematic review and meta-analysis.

To investigate the performance of severe smallness in the prediction of adverse perinatal outcome among fetuses with suspected late-onset small-for-gestational age (SGA). A systematic search was performed to identify relevant studies in PubMed, Web of Science and Scopus. Late-onset SGA was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile diagnosed at or after 32 weeks' gestation, while severe SGA was defined as EFW or AC < 3rd percentile or < 2 SD. Random-effects modeling was used to generate hierarchical summary receiver-operating-characteristics (HSROC) curves. The performance of severe SGA (as a presumptive diagnosis) in predicting adverse perinatal outcome among singleton pregnancies with suspected late-onset SGA was expressed as area under the HSROC curve (AUC), sensitivity, specificity and positive/negative likelihood ratios. The association between suspected severe SGA and adverse perinatal outcome was also assessed by random-effects modeling using the Mantel-Haenszel method and presented as odds ratio (OR). The non-exposed group was defined as non-severe SGA (EFW ≥ 3rd centile). Twelve cohort studies were included in this systematic review and meta-analysis. The studies included a total of 3639 fetuses with suspected late-onset SGA, of which 1246 had suspected severe SGA. Significant associations were found between suspected severe SGA and composite adverse perinatal outcome (OR, 1.97 (95% CI, 1.33-2.92)), neonatal intensive care unit admission (OR, 2.87 (95% CI, 1.84-4.47)) and perinatal death (OR, 4.26 (95% CI, 1.07-16.93)). However, summary ROC curves showed limited performance of suspected severe SGA in predicting perinatal outcomes, with AUCs of 60.9%, 66.9%, 53.6%, 57.2%, 54.6% and 64.9% for composite adverse perinatal outcome, neonatal intensive care unit admission, neonatal acidosis, Cesarean section for intrapartum fetal compromise, low Apgar score and perinatal death, respectively. Although suspected severe SGA was associated with a higher risk of perinatal complications, it performed poorly as a standalone parameter in predicting adverse perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Evidence of Maternal Antibodies Elicited by COVID-19 Vaccination in Amniotic Fluid: Report of Two Cases in Italy

With SARS-CoV-2 infection, pregnant women may be at a high risk of severe disease and adverse perinatal outcomes. A COVID-19 vaccination campaign represents the key strategy to combat the pandemic; however, public acceptance of maternal immunization has to be improved, which may be achieved by highlighting the promising mechanism of passive immunity as a strategy for protecting newborns against SARS-CoV-2 infection. We tested the anti-SARS-CoV-2 antibody response following COVID-19 full-dose vaccination in the serum and amniotic fluid of two pregnant women who presented between April and June 2021, at the Center for the Treatment and Prevention of Infections in Pregnancy of the National Institute for Infectious Diseases “L. Spallanzani”, for antenatal consultancy. Anti-SARS-CoV-2 IgG was found in residual samples of amniotic fluid collected from both women at the 18th week of gestation (63 and 131 days after the second dose’s administration). Titers in amniotic fluid mirrored the levels detected in serum and were inversely linked to the time from vaccination. Our results suggest that antibodies elicited by COVID-19 vaccination can cross the placenta and reach the fetus; therefore, they may offer passive immunity at birth. It is critical to fully understand the kinetics of the maternal response to vaccination, the efficiency of IgG transfer, and the persistence of antibodies in infants to optimize maternal immunization regimens.

Epidemiology of placenta accreta spectrum disorders in Chinese pregnant women: A multicenter hospital-based study

IntroductionPlacenta accreta spectrum disorder (PASD) is a life-threatening obstetric complication. China still lacks high-quality data on the epidemiology of PASD. We intend to examine the major risk factors for PASD, explore the association of PASD with severe adverse perinatal outcomes and describe the geographical variations in China. MethodsWe used data from the China Labor and Delivery Survey, which included a total of 75,132 births from 96 hospitals in 24 provinces in China in 2015 and 2016. Each participating hospital randomly selected 6–10 weeks within a 12-month period. In the selected weeks, all births with gestational age ≥24 weeks or birth weight ≥500 g were included. We analyzed the demographic characteristics and prevalence of PASD in pregnant women. Multivariable logistic regression was used to examine the association of previous caesarean section (CS) and repeated surgical abortion with PASD. We explored the association of PASD with severe adverse perinatal outcomes, which indicated by Weighted Adverse Outcome Score (WAOS) ≥ 20. Multivariable logistic regression was used to examine the association of PASD with WAOS. We also calculated and compared the prevalence of PASD in different regions of China. ResultsThe weighted prevalence of PASD was 2.20% (95% CI 0.76 to 4.95) in our population，and there was a substantial difference in the prevalence of PASD by geographic regions in China. Two or more previous CS (adjusted OR 2.34, 95%CI 1.41 to 3.88) and repeated surgical abortion (twice: 2.16, 1.20 to 3.92; 3 times: 4.31, 1.70 to 10.96; ≥4 times: 4.76, 3.12 to 7.26) were significant risk factors for PASD. PASD (adjusted OR 3.77, 95% CI 2.80 to 5.06) was a significant risk factor for severe adverse perinatal outcomes indicated by WAOS score. DiscussionThe prevalence of PASD in China appeared higher than that in other countries, and varied substantially by geographic regions. Two or more previous CS and repeated surgical abortion were major risk factors for PASD. Pregnant women with PASD had more severe adverse pregnancy outcomes. Reducing primary cesarean section and repeated surgical abortion are the key to decreasing PASD.

Associations of severe adverse perinatal outcomes among continuous birth weight percentiles on different birth weight charts: a secondary analysis of a cluster randomized trial

ObjectiveTo identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart.BackgroundGrowth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management.MethodsThis is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included.We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes.Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis.ResultsWe found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low.ConclusionsThe clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk.Trial RegistrationNetherlands Trial Register NTR4367.Registration date March 20th, 2014.

Diagnosis of proteinuria using a random urine protein-creatinine ratio and its correlation with adverse outcomes in pregnancy with preeclampsia characterized by renal damage.

Based on a limited number of studies, a random urine protein‐creatinine ratio (uPCR) value of ≥ 0.3 indicates abnormal proteinuria in preeclampsia with renal damage. However, current guidelines do not recommend a reasonable diagnostic threshold of uPCR for severe preeclampsia with renal damage. Furthermore, the correlation between the uPCR value and clinical adverse outcomes remains poorly understood. The aim of the present study was to evaluate the value of uPCR in the diagnosis of significant proteinuria and to assess its correlation with adverse pregnancy outcomes in preeclampsia characterized by renal damage. In all, 1837 women were enrolled in this retrospective cohort study. Eventually, 961 women were enrolled under the exclusion criteria. First, the authors found that uPCR and 24‐hour proteinuria showed a significant association (r = 0.901). The optimal threshold of uPCR for diagnosing preeclampsia was 0.295, and for diagnosing severe preeclampsia the cut‐off was 0.625. Meanwhile, the adjusted odds ratio per 1 unit increase in ln (uPCR) was 1.679 (95% confidence interval [CI]:1.142–2.469) for severe adverse perinatal outcomes; 1.456 (95% CI: 1.242–1.705) for small for gestational age; 1.380 (95% CI: 1.051–1.811) for severe small for gestational age; 1.672 (95% CI: 1.210–2.310) for very early preterm birth; 1.989 (95% CI 1.726–2.293) for severe hypertension; and 2.279 (95% CI 1.906–2.724) for preterm birth. This study indicated that there was a significant and positive correlation between uPCR and 24‐hour urine protein. For neonatal and maternal adverse outcomes, uPCR is an independent predictor of prognosis.